WorldWideScience

Sample records for soluble il-2r levels

  1. Soluble intercellular adhesion molecule-1 (sICAM-1) and soluble interleukin-2 receptors (sIL-2R) in scleroderma skin

    DEFF Research Database (Denmark)

    Søndergaard, Klaus; Deleuran, Mette; Heickendorff, Lene

    1998-01-01

    In order to investigate whether soluble intercellular adhesion molecule-1 (sICAM-1) and soluble interleukin-2 receptors (sIL-2R) were present in scleroderma skin, and to compare their levels to concentrations measured in plasma and clinical parameters, we examined suction blister fluid and plasma...... from 13 patients with systemic sclerosis and 11 healthy volunteers. Suction blisters and biopsies were from the transition zone between normal skin and scleroderma, and uninvolved abdominal skin. The levels of sICAM-1 and sIL-2R were significantly increased in both plasma and suction blister fluid from...

  2. Biological significance of soluble IL-2 receptor

    Directory of Open Access Journals (Sweden)

    Calogero Caruso

    1993-01-01

    Full Text Available A NUMBER of receptors for growth factors and differentiation antigens have been found to be secreted or released by cells. Following mononuclear cell (MNC activation and interleukin-2 receptor (IL-2R expression, a soluble form of the Alpha;-chain of IL-2R (sIL-2R is released. The sIL-2R has been shown to be present in the culture supernatants of activated MNCs as well as in normal sera and, in higher amounts, in sera from subjects affected by several diseases including neoplastic, infectious and autoimmune ones, and in sera from transplanted patients suffering allograft rejection. The blood sIL-2R levels depend on the number of producing cells and the number of molecules per cell, so that sIL-2R blood values may represent an index of the number and the functional state of producing cells, both normal and neoplastic. Thus, monitoring of the immune system, mostly T-cells and haematological malignancies might be targets for the measurement of sIL-2R. Since many conditions may influence sIL-2R production, little diagnostic use may result from these measurements. However, since blood sIL-2R levels may correlate with disease progression and/or response to therapy, their measurement may be a useful index of activity and extent of disease. The precise biological role of the soluble form of the IL-2R is still a matter of debate. However, we know that increased sIL-2R levels may be observed in association with several immunological abnormalities and that sIL-2R is able to bind IL-2. It is conceivable then that in these conditions the excess sIL-2R released in vivo by activated lymphoid cells or by neoplastic cells may somehow regulate IL-2-dependent processes. On the other hand, it cannot exclude that sIL-2R is a by-product without biological significance. Finally, it is puzzling that in many conditions in which an increase of blood sIL-2R values has been observed, MNCs display a decreased in vitro capacity to produce sIL-2R. These seemingly contrasting

  3. Changes of serum IL-1 and sIL-2R levels after intravenous photo-coagulation in patients with varicose greater saphenous vein

    International Nuclear Information System (INIS)

    Han Li'na; Gu Ying; Liu Fanguang

    2004-01-01

    Objective: To determine the changes of serum interleukin 2 (IL-2) and soluble interleukin 2 receptor (sIL-2R) levels in patients with varicose greater saphenous vein after intravenous photocoagulation. Methods: Fifty patients with varicose greater saphenous vein were divided into two groups (mild and severe) according to their clinical symptoms. Serum IL-2 and sIL-2R levels were determined with RIA and ELISA respectively in these patients and 30 controls. Results: Serum levels of IL-2 and sIL-2R in patients of the mild group were about the same as those in the controls. In patients of the severe group, levels of IL-2 decreased and levels of sIL-2R increased significantly. After photocoagulation, the IL-2 levels dropped at first but gradually rose; the reverse was true for the sIL-2R levels. The final levels of IL-2 and sIL-2R approached those before treatment in the mild group. In the severe group, the final IL-2 levels were higher and sIL-2R levels lower than those before photocoagulation. Conclusion: Determination of serum IL-2 and sIL-2R levels revealed information about the immune status of the patients and could be applied for judgement of the treatment effect

  4. Clinical significance of the changes of serum levels of the rheumatoid activity markers IL-2, sIL-2R, HA and VEGF

    International Nuclear Information System (INIS)

    Bao Yong; Long Wubin; Yu Ke; Zeng Ying; Liu Deying

    2004-01-01

    Objective: To explore the relationship between rheumatoid activity and serum levels of the cytokines interleukin-2 (IL-2), soluble interleukin-2 receptor (sIL-2R), hyaluronic acid (HA), vascular endothelial growth factor (VEGF) in patients with rheumatoid arthritis. Methods: Serum IL-2, HA(with RIA) and sIL-2R, VEGF (with ELISA) levels were determined in 30 controls, 30 patients with active rheumatoid arthritis and 30 patients with rheumatoid arthritis in remission. Sensitivity and specificity for each marker were analyzed. Results: In patients with active rheumatoid arthritis, the serum levels of sIL-2R, HA, VEGF were significantly higher and serum levels of IL-2 significantly lower than those in patients in remission and controls (p<0.01). Determination of VEGF levels possessed the highest specificity (93.3%) and also a high sensitivity (93.3% as well). Conclusion: Determination of the serum levels of any of these markers was valuable for monitoring the activity of the rheumatoid process. It is more desirable to take measurements of VEGF levels due to its highest specificity

  5. Reliability of soluble IL-2 receptor measurements obtained with enzyme-linked immunosorbent assay

    International Nuclear Information System (INIS)

    Akiyama, Mitoshi; Takaishi, Masatoshi; Murakami, Yoshie; Ueda, Ryuzo; Yamakido, Michio; Tsubokura, Tokuo.

    1989-09-01

    Using an enzyme-linked immunosorbent assay (ELISA), human soluble interleukin-2 receptors (IL-2R) were measured in the serum of patients with various autoimmune system diseases. To study the sensitivity and specificity of the assay, soluble IL-2Rs were measured in the culture supernatants and in the cell extracts of peripheral blood mononuclear cells activated with phytohemagglutinin (PHA), purified protein derivative of tuberculin, and allogeneic lymphocytes, as well as in the serum of patients with various collagen diseases. The results correlated well with reports from other laboratories. For example, when stimulated by PHA, the greatest amount of soluble IL-2Rs was produced at the fastest rate. In addition, soluble IL-2R levels in the serum of collagen disease patients were significantly higher than those in healthy persons, who themselves exhibited low levels of detectable soluble IL-2Rs. It is hoped that reliable ELISA measurements of soluble IL-2Rs in the serum of atomic bomb survivors will assist in the interpretation of data collected during the work described in RP 2-87, a study of autoimmunity and autoimmune diseases in the Adult Health Study. (author)

  6. Clinical significance of the changes of serum IL-2, SIL-2R and VEGF levels in pediatric patients with pulmonary tuberculosis

    International Nuclear Information System (INIS)

    Zeng Dongliang; Wu Chunfeng; Jiang Huanhao

    2005-01-01

    Objective: To explore the clinical significance of the changes of serum IL-2, soluble IL-2 receptor (SIL-2R) and vascular endothelial growth factor (VEGF) levels in pediatric patients with tuberculosis. Methods: Serum IL-2 (with RIA) and SIL-2R, VEGF (with ELISA) levels were determined in 68 pediatric patients with tuberculosis (30 active and 38 non- active) and 30 controls. Results: In the patients with active tuberculosis, the serum IL-2 levels were significantly lower and SIL-2R, VEGF levels were significantly higher than those in the controls (P<0.01). Conclusion: Determination of serum IL-2, SIL-2R and VEGF levels was useful for monitoring the activity of tuberculosis in pediatric patients. (authors)

  7. Elevated Plasma Levels of sIL-2R in Complex Regional Pain Syndrome: A Pathogenic Role for T-Lymphocytes?

    Directory of Open Access Journals (Sweden)

    Krishna D. Bharwani

    2017-01-01

    Full Text Available The immune system has long been thought to be involved in the pathophysiology of complex regional pain syndrome (CRPS. However, not much is known about the role of the immune system and specifically T-cells in the onset and maintenance of this disease. In this study, we aimed to evaluate T-cell activity in CRPS by comparing blood soluble interleukin-2 receptor (sIL-2R levels between CRPS patients and healthy controls. CRPS patients had statistically significant elevated levels of sIL-2R as compared to healthy controls (median sIL-2R levels: 4151 pg/ml (Q3 − Q1 = 5731 pg/ml − 3546 pg/ml versus 1907 pg/ml (Q3 − Q1: 2206 pg/ml − 1374 pg/ml, p<0.001, resp.. Furthermore, sIL-2R level seems to be a good discriminator between CRPS patients and healthy controls with a high sensitivity (90% and specificity (89.5%. Our finding indicates increased T-cell activity in patients with CRPS. This finding is of considerable relevance as it could point towards a T-cell-mediated inflammatory process in this disease. This could pave the way for new anti-inflammatory therapies in the treatment of CRPS. Furthermore, sIL-2R could be a promising new marker for determining inflammatory disease activity in CRPS.

  8. Clinical significance of determination of changes of serum IL-2, sIL-2R and TGF-β levels in patients with Graves' ophthalmopathy

    International Nuclear Information System (INIS)

    Li Han

    2009-01-01

    Objective: To study the relationship between progress of the disease and the changes of serum IL-2, sIL-2R and TGF-β levels in patients with Graves' ophthalmopathy. Methods: Serum TGF-β(with RIA) and IL-2, sIL-2R(with ELISA) levels were determined in 30 patients with Graves' ophthalmopathy both before and after six months' treatment with prednisonlone as well as in 30 controls. Results: The serum IL-2 levels in the patients before treatment were significantly lower than those in controls (P 0.05). Both serum sIL-2R and TGF-β levels in the patients before treatment were significantly higher than those in controls (P<0.01). After treatment, the levels dropped markedly, but still remained significantly higher than those in controls (P<0.05 and P<0.01). Conclusion: Determination of changes of serum IL-2, sIL-2R and TGF-β levels in patients with Graves' ophthalmopathy might be helpful for outcome prediction. (authors)

  9. Clinical significance of determination of changes of serum EMAb, IL-2, IL-2R and VEGF levels in patients with endometriosis

    International Nuclear Information System (INIS)

    Min Jieyan

    2009-01-01

    Objective: To investigate the relationship between the progress of the disease process and changes of serum antiendome-trium antibody (EMAb), interleukin-2 (IL-2), interleukin-2 receptor (IL-2R) and vascular endothelial growth factor (VEGF) levels in patients with endometriosis. Methods: Serum EMAb (with ELISA) and VEGF, IL-2, IL-2R (with RIA) levels were measured in 45 patients with endometriosis both before and after treatment as well as in 35 controls. Results: Before treatment with integrated traditional and western medicine, the positive rate of serum EMAb were significantly higher in patients with endometriosis than that in the controls (P 0.05). Conclusion: Determination of changes of serum EMAb, IL-2, IL-2R and VEGF levels in patients with endometriosis were helpful for assessment of the progress of disease process and outcome prediction. (authors)

  10. Elevated Plasma Levels of sIL-2R in Complex Regional Pain Syndrome: A Pathogenic Role for T-Lymphocytes?

    Science.gov (United States)

    Stronks, Dirk L.; Dik, Willem A.; Schreurs, Marco W. J.

    2017-01-01

    The immune system has long been thought to be involved in the pathophysiology of complex regional pain syndrome (CRPS). However, not much is known about the role of the immune system and specifically T-cells in the onset and maintenance of this disease. In this study, we aimed to evaluate T-cell activity in CRPS by comparing blood soluble interleukin-2 receptor (sIL-2R) levels between CRPS patients and healthy controls. CRPS patients had statistically significant elevated levels of sIL-2R as compared to healthy controls (median sIL-2R levels: 4151 pg/ml (Q3 − Q1 = 5731 pg/ml − 3546 pg/ml) versus 1907 pg/ml (Q3 − Q1: 2206 pg/ml − 1374 pg/ml), p CRPS patients and healthy controls with a high sensitivity (90%) and specificity (89.5%). Our finding indicates increased T-cell activity in patients with CRPS. This finding is of considerable relevance as it could point towards a T-cell-mediated inflammatory process in this disease. This could pave the way for new anti-inflammatory therapies in the treatment of CRPS. Furthermore, sIL-2R could be a promising new marker for determining inflammatory disease activity in CRPS. PMID:28634419

  11. Antigen-specific murine T cell clones produce soluble interleukin 2 receptor on stimulation with specific antigens

    International Nuclear Information System (INIS)

    Wagner, D.K.; York-Jolley, J.; Malek, T.R.; Berzofsky, J.A.; Nelson, D.L.

    1986-01-01

    In this study, monoclonal antibodies were used to the murine IL 2 receptor (IL 2R) termed 3C7 and 7D4, which bind to different epitopes on the murine IL 2R, to develop an ELISA to measure soluble murine IL 2R. Surprisingly, stimulated murine spleen cells not only expressed cell-associated IL 2R, but also produced a considerable level of cellfree IL 2R in the culture supernatant fluid. To assess the fine specificity of this response, myoglobin-immune murine T cell clones were stimulated with appropriate or inappropriate antigen and syngeneic or allogeneic presenting cells. Proliferation, measured by [ 3 H] thymidine incorporation, and levels of soluble IL 2R were determined at day 4. The production of soluble IL2R displayed the same epitope fine specificity, genetic restriction, and antigen dose-response as the proliferative response. Indeed, in some cases there was sharper discrimination of epitope specificity and genetic restriction with the soluble IL 2R levels. There was also reproducible clone-to-clone variation in the amount of soluble receptor produced in response to antigen among 12 T cell clones and lines tested. In time course experiments, proliferation was greatest at day 3, whereas soluble IL 2R levels continued to rise in subsequent days. To the authors' knowledge, this is the first demonstration of release of secretion of soluble IL 2R by murine T cells, and the first demonstration of the fine specificity and genetic restriction of the induction of soluble IL 2R by specific antigen

  12. Clinical significance of measurement of changes of serum IL-2, SIL-2R levels after chemotherapy in patients with lung carcinoma

    International Nuclear Information System (INIS)

    Lu Men; Duo Huanzhi; Luo Guorong

    2004-01-01

    Objective: To study the changes of serum IL-2 and SIL-2R levels after chemotherapy in 36 patients with lung carcinoma. Methods: Serum IL-2 (with RIA) and SIL-2R (with ELISA) levels were measured in 36 patients with lung carcinoma both before and after chemotherapy as well as in 35 controls. Results: Before chemotherapy, in the patients the serum IL-2 levels were significantly lower and serum SIL-2R levels were significantly higher than those in the controls (P<0.01). Six months after chemotherapy, those patients without recurrence (n=20) had their IL-2 and SIL-2R levels returned to normal but in those with recurrences (n=12) the levels were about the same as before. Conclusion: Cytokines IL-2 and SIL-2R levels changes could reflect the immunostatus of the patient as well as the progress of disease and could be of prognostic value. (authors)

  13. Clinical significance of measurement of changes of serum IL-2, SIL-2R levels after treatment in patients with thrombocytopenic purpura

    International Nuclear Information System (INIS)

    Feng Yue

    2005-01-01

    Objective: To study the changes of serum IL-2 and SIL-2R levels after treatment in 31 patients with thrombocytopenic purpura. Methods: Serum IL-2 (with RIA) and SIL-2R (with ELISA) levels were measured in 31 patients with thrombocytopenic purpura both before and after treatment as well as in 35 controls. Results: Before treatment, in the patients the serum IL-2 levels were significantly lower and serum SIL-2R levels were significantly higher than those in the controls ( P 0.05). Conclusion: Cytokines IL-2 and SIL-2R levels changes could reflect the immunostatus of the patients as well as the progress of diseases and could be of prognostic values. (authors)

  14. Soluble interleukin 6 receptor (sIL-6R) mediates colonic tumor cell adherence to the vascular endothelium: a mechanism for metastatic initiation?

    LENUS (Irish Health Repository)

    Dowdall, J F

    2012-02-03

    The mechanisms by which surgery increases metastatic proliferation remain poorly characterized, although endotoxin and immunocytes play a role. Recent evidence suggests that endothelial adherence of tumor cells may be important in the formation of metastases. Soluble receptors of interleukin-6 (sIL-6R) shed by activated neutrophils exert IL-6 effects on endothelial cells, which are unresponsive under normal circumstances. This study examined the hypothesis that sIL-6R released by surgical stress increases tumor cell adherence to the endothelium. Neutrophils (PMN) were stimulated with lipopolysaccharide, C-reactive protein (CRP), and tumor necrosis factor-alpha. Soluble IL-6R release was measured by enzyme-linked immunosorbent assay. Colonic tumor cells transfected with green fluorescent protein and endothelial cells were exposed to sIL-6R, and tumor cell adherence and transmigration were measured by fluorescence microscopy. Basal release of sIL-6R from PMN was 44.7 +\\/- 8.2 pg\\/ml at 60 min. This was significantly increased by endotoxin and CRP (131 +\\/- 16.8 and 84.1 +\\/- 5.3, respectively; both P < 0.05). However, tumor necrosis factor-alpha did not significantly alter sIL-6R release. Endothelial and tumor cell exposure to sIL-6R increased tumor cell adherence by 71.3% within 2 h but did not significantly increase transmigration, even at 6 h. Mediators of surgical stress induce neutrophil release of a soluble receptor for IL-6 that enhances colon cancer cell endothelial adherence. Since adherence to the endothelium is now considered to be a key event in metastatic genesis, these findings have important implications for colon cancer treatment strategies.

  15. Quantitative Contribution of IL2Rγ to the Dynamic Formation of IL2-IL2R Complexes.

    Directory of Open Access Journals (Sweden)

    Luis F Ponce

    Full Text Available Interleukin-2 (IL2 is a growth factor for several immune cells and its function depends on its binding to IL2Rs in the cell membrane. The most accepted model for the assembling of IL2-IL2R complexes in the cell membrane is the Affinity Conversion Model (ACM. This model postulates that IL2R receptor association is sequential and dependent on ligand binding. Most likely free IL2 binds first to IL2Rα, and then this complex binds to IL2Rβ, and finally to IL2Rγ (γc. However, in previous mathematical models representing this process, the binding of γc has not been taken into account. In this work, the quantitative contribution of the number of IL2Rγ chain to the IL2-IL2R apparent binding affinity and signaling is studied. A mathematical model of the affinity conversion process including the γ chain in the dynamic, has been formulated. The model was calibrated by fitting it to experimental data, specifically, Scatchard plots obtained using human cell lines. This paper demonstrates how the model correctly explains available experimental observations. It was estimated, for the first time, the value of the kinetic coefficients of IL2-IL2R complexes interaction in the cell membrane. Moreover, the number of IL2R components in different cell lines was also estimated. It was obtained a variable distribution in the number of IL2R components depending on the cell type and the activation state. Of most significance, the study predicts that not only the number of IL2Rα and IL2Rβ, but also the number of γc determine the capacity of the cell to capture and retain IL2 in signalling complexes. Moreover, it is also showed that different cells might use different pathways to bind IL2 as consequence of its IL2R components distribution in the membrane.

  16. Clinical significance of measurements of changes of serum IL-2, SIL-2R, TNF-α levels after chemotherapy in patients with ovary cancer

    International Nuclear Information System (INIS)

    Ma Zhongwei

    2005-01-01

    Objective: To study the changes of serum IL-2, SIL-2R and TNF-α levels after chemotherapy in 34 patients with ovary cancer. Methods: Serum IL-2, TNF-α (with RIA) and SIL-2R (with ELISA) levels were measured in 34 patients with ovary cancers both before and 6 months after chemotherapy as well as in 30 controls. Results: Before chemotherapy in the patients the serum IL-2 levels were significantly lower and serum SIL-2R and TNF-α levels were significantly higher than those in the controls (P<0.01). Six months after chemotherapy, those patients without recurrence (n=21) had their IL-2, SIL-2R and TNF-α levels returned to normal, but in those with recurrences (n=10) the levels were about the same as before. Conclusion: Serum IL-2, SIL-2R and TNF-α levels changes could reflect the immunostatus of the patients as well as the progress of diseases and could be of prognostic value. (authors)

  17. Structure of IL-22 Bound to Its High-Affinity IL-22R1 Chain

    Energy Technology Data Exchange (ETDEWEB)

    Jones, B.C.; Logsdon, N.J.; Walter, M.R. (UAB)

    2008-09-29

    IL-22 is an IL-10 family cytokine that initiates innate immune responses against bacterial pathogens and contributes to immune disease. IL-22 biological activity is initiated by binding to a cell-surface complex composed of IL-22R1 and IL-10R2 receptor chains and further regulated by interactions with a soluble binding protein, IL-22BP, which shares sequence similarity with an extracellular region of IL-22R1 (sIL-22R1). IL-22R1 also pairs with the IL-20R2 chain to induce IL-20 and IL-24 signaling. To define the molecular basis of these diverse interactions, we have determined the structure of the IL-22/sIL-22R1 complex. The structure, combined with homology modeling and surface plasmon resonance studies, defines the molecular basis for the distinct affinities and specificities of IL-22 and IL-10 receptor chains that regulate cellular targeting and signal transduction to elicit effective immune responses.

  18. Clinical significance of measurements of changes of serum IL-2, SIL-2R and TNF-α levels after treatment in patients with rheumatoid arthritis

    International Nuclear Information System (INIS)

    Yu Songsan

    2007-01-01

    Objective: To study the changes of serum IL-2, SIL-2R and TNF-α levels after treatment in 39 patients with rheumatoid arthritis. Methods: Serum IL-2, TNF-α (with RIA) and SIL-2R (with ELISA) levels were measured in 39 patients with rheumatoid arthritis. Both before and one year after treatment as well as in 35 controls. Results: Before treatment in the patients the serum IL-2 levels were significantly lower and serum SIL-2R and TNF-α levels, were significantly higher than those in the controls (P<0.01), one year after treatment, the patients without recurrence (n=31) had their serum IL-2, SIL-2R and TNF-α levels returned to normal, but in patients with recurrences (n=8) the levels were about the same as those before treatment. Conclusion: Serum IL-2, SIL-2R and TNF-α lends were closely related to the diseases process and could be of prognostic value. (authors)

  19. Purification, crystallization and preliminary X-ray diffraction analysis of the IL-20-IL-20R1-IL-20R2 complex

    Energy Technology Data Exchange (ETDEWEB)

    Logsdon, Naomi J.; Allen, Christopher E.; Rajashankar, Kanagalaghatta R.; Walter, Mark R. (Cornell); (UAB)

    2012-02-08

    Interleukin-20 (IL-20) is an IL-10-family cytokine that regulates innate and adaptive immunity in skin and other tissues. In addition to protecting the host from various external pathogens, dysregulated IL-20 signaling has been shown to contribute to the pathogenesis of human psoriasis. IL-20 signals through two cell-surface receptor heterodimers, IL-20R1-IL-20R2 and IL-22R1-IL-20R2. In this report, crystals of the IL-20-IL-20R1-IL-20R2 ternary complex have been grown from polyethylene glycol solutions. The crystals belonged to space group P4{sub 1}2{sub 1}2 or P4{sub 3}2{sub 1}2, with unit-cell parameters a = 111, c = 135 {angstrom}, and diffracted X-rays to 3 {angstrom} resolution. The crystallographic asymmetric unit contains one IL-20-IL-20R1-IL-20R2 complex, corresponding to a solvent content of approximately 54%.

  20. Clinical significance of determination of changes of serum IL-2, SIL-2R and TNF-α levels after treatment in patients with endometriosis

    International Nuclear Information System (INIS)

    Shao Xuefeng; Li Linlin; Shao Jun; Yao Hui

    2008-01-01

    Objective: To explore the clinical significance of changes of serum IL-2, SIL-2R and TNF-α levels after treatment in patients with endometriosis. Methods: Serum IL-2 and TNF-α (with RIA) and SIL-2R (with ELISA) levels were determined in 42 patients with endometriosis both before and after treatment as well as in 35 controls. Results: Before treatment, the serum SIL-2R and TNF-α levels in patients were significantly higher than those in the controls (P 0.05). Conclusion: Development of endometriosis were closely related to the serum levels of IL-2, SIL-2R and TNF-α. (authors)

  1. Decreased plasma levels of factor II + VII + X correlate with increased levels of soluble cytokine receptors in patients with malaria and meningococcal infections

    DEFF Research Database (Denmark)

    Bygbjerg, I C; Hansen, M B; Rønn, A M

    1997-01-01

    The levels of coagulation factors II + VII + X and of blood platelets (thrombocytes) as well as of cytokines and soluble cytokine receptors were studied in the patients with malaria or meningococcal infections. The coagulation factors were decreased particularly in the meningococcal patients, while...... thrombocytes were lowest in the Plasmodium falciparum malaria patients. There was no correlation between factors II + VII + X and thrombocytes, but plasma levels of coagulation factors II + VII + X were found to correlate inversely with levels of soluble interleukin-2 receptor (sIL-2R) and soluble tumour...... necrosis factor-I (sTNF-RI) in patients with malaria and meningococcal infections. Elevated sIL-2R and sTNF-RI levels and decreased coagulation factors reverted to normal within 3-5 days after initiation of therapy in P. falciparum patients followed consecutively. Estimation of coagulation factors may...

  2. A soluble form of IL-13 receptor alpha 1 promotes IgG2a and IgG2b production by murine germinal center B cells.

    Science.gov (United States)

    Poudrier, J; Graber, P; Herren, S; Gretener, D; Elson, G; Berney, C; Gauchat, J F; Kosco-Vilbois, M H

    1999-08-01

    A functional IL-13R involves at least two cell surface proteins, the IL-13R alpha 1 and IL-4R alpha. Using a soluble form of the murine IL-13R alpha 1 (sIL-13R), we reveal several novel features of this system. The sIL-13R promotes proliferation and augmentation of Ag-specific IgM, IgG2a, and IgG2b production by murine germinal center (GC) B cells in vitro. These effects were enhanced by CD40 signaling and were not inhibited by an anti-IL4R alpha mAb, a result suggesting other ligands. In GC cell cultures, sIL-13R also promoted IL-6 production, and interestingly, sIL-13R-induced IgG2a and IgG2b augmentation was absent in GC cells isolated from IL-6-deficient mice. Furthermore, the effects of the sIL-13R molecule were inhibited in the presence of an anti-IL-13 mAb, and preincubation of GC cells with IL-13 enhanced the sIL-13R-mediated effects. When sIL-13R was injected into mice, it served as an adjuvant-promoting production to varying degrees of IgM and IgG isotypes. We thus propose that IL-13R alpha 1 is a molecule involved in B cell differentiation, using a mechanism that may involve regulation of IL-6-responsive elements. Taken together, our data reveal previously unknown activities as well as suggest that the ligand for the sIL-13R might be a component of the IL-13R complex or a counterstructure yet to be defined.

  3. Decreased concentrations of soluble interleukin-1 receptor accessory protein levels in the peritoneal fluid of women with endometriosis.

    Science.gov (United States)

    Michaud, Nadège; Al-Akoum, Mahéra; Gagnon, Geneviève; Girard, Karine; Blanchet, Pierre; Rousseau, Julie Anne; Akoum, Ali

    2011-12-01

    Interleukin 1 (IL1) may play an important role in endometriosis-associated pelvic inflammation, and natural specific inhibitors, including soluble IL1 receptor accessory protein (sIL1RAcP) and soluble IL1 receptor type 2 (sIL1R2), are critical for counterbalancing the pleiotropic effects of IL1. The objective of this study was to evaluate the levels of sIL1RAcP, together with those of sIL1R2 and IL1β, in the peritoneal fluid of women with and without endometriosis. Peritoneal fluid samples were obtained at laparoscopy and assessed by ELISA. sIL1RAcP concentrations were reduced in endometriosis stages I-II and III-IV. sIL1R2 concentrations were decreased, and those of IL1β were significantly increased in endometriosis stages I-II. sIL1RAcP and sIL1R2 concentrations were significantly decreased in the secretory phase of the menstrual cycle, and IL1β concentrations were elevated in the proliferative and the secretory phases. sIL1RAcP and sIL1R2 concentrations were reduced in women with endometriosis who were infertile, fertile, suffering from pelvic pain or pain-free. However, IL1β concentrations were significantly reduced in women with endometriosis who were infertile or had pelvic pain. These changes may exacerbate the local peritoneal inflammatory reaction observed in women with endometriosis and contribute to endometriosis pathophysiology and the major symptoms of this disease. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  4. Immunosuppressive effect of the anti-IL-2-receptor monoclonal antibody, AMT-13, on organ-cultured fetal pancreas allograft survival

    International Nuclear Information System (INIS)

    Burkhardt, K.; Loughnan, M.S.; Diamantstein, T.; Mandel, T.E.

    1988-01-01

    Recently, prolongation of cardiac allograft survival in mice was reported using a rat anti-IL-2R mAb (AMT-13). However, its immunosuppressive action in vivo, alone and in combination with other immunosuppressants, and its effect on other organ transplants has not been extensively studied. We grafted cultured fetal pancreas from CBA (H-2k) donors to Balb/c (H-2d) mice. Recipients were treated with 10 consecutive daily injections each of 20 micrograms AMT-13 only, or with an additional mild immunosuppression of 350 rads irradiation. Control groups received rat immunoglobulin or 350 rads irradiation. Graft survival and the phenotype of infiltrating cells were assessed histologically and immunocytochemically on days 12, 17, and 21, and soluble IL-2R levels were measured in the serum with a quantitative ELISA in all recipients. Two of five grafts in the AMT-13-treated group had islets on day 12 posttransplantation despite lymphocytic infiltration in all grafts, while at this time all grafts of rat Ig treated control mice were completely rejected with only scar tissue and a few lymphocytes remaining. Additional immunosuppression with 350 rads irradiation had a marked additive effect with AMT-13. Soluble IL-2R levels in the serum of untreated recipients were not elevated compared with normal serum levels, but recipients injected with AMT-13 had multifold increased soluble IL-2R levels. The percentage of IL-2R+ cells in the grafts of AMT-13-treated animals was either normal (less than 5%) or increased (20%) in the additionally irradiated mice, providing strong evidence that the immunosuppressive effect of AMT-13 is not due to a depletion of activated IL-2R+ lymphocytes

  5. Intrathymic radioresistant stem cells follow an IL-2/IL-2R pathway during thymic regeneration after sublethal irradiation

    International Nuclear Information System (INIS)

    Zuniga-Pfluecker, J.C.K.; Kruisbeek, A.M.

    1990-01-01

    Sublethally irradiated mice undergo thymic regeneration which follows a phenotypic pattern of events similar to that observed during normal fetal development. Thymic regeneration after irradiation is the product of a limited pool of intrathymic radioresistant stem cells undergoing simultaneous differentiation. We show that in this model of T cell development, thymic regeneration follows a pathway in which the IL-2R is transiently expressed on CD4-/CD8- cells. IL-2R expression occurred during the exponential growth period of thymic regeneration, and IL-2R blocking prevented this explosive growth. Flow cytometry analysis revealed that the IL-2R blockade affected primarily the development of the immature CD3-/CD4-/CD8- (triple negative) cells and their ability to generate CD3+/CD4+/CD8+ or CD3+/CD4+/CD8- and CD3+/CD4-/CD8+ thymocytes. Thus, our findings demonstrate that blocking of the IL-2R resulted in an arrest in proliferation and differentiation by intrathymic radioresistant stem cells, indicating that the IL-2/IL-2R pathway is necessary for the expansion of immature triple negative T cells

  6. Relationship between XspI Site Polymorphisms of LDL-R Gene and Serum IL-2 and IL-10 in Patients with Hypercholesterolemia.

    Science.gov (United States)

    Zhang, Mingming; Lu, Yamin; Liu, Xin; Zhang, Xiaobin; Zhang, Cuigai; Gao, Wei; Tie, Yanqing

    2016-11-01

    Relationship has been identified in sporadic reports between polymorphisms and hypercholesterolemia. However, the relationship between inflammatory cytokines and polymorphism of low-density lipoprotein receptor (LDL-R) gene in hypercholesterolemia is unclear. This study aimed to explore the relationship and significance between polymorphisms of LDL-R gene and serum Interleukin-2 (IL-2), IL-10 in patients with hypercholesterolemia. PCR-RFLP and direct DNA sequencing assay were employed to determine polymorphism of LDL-R gene in 900 patients with hypercholesterolemia and 400 healthy cases. ELISA was applied to assay serum concentration of IL-2 and IL-10. Blood lipid indexes were tested in all cases. Compared with the healthy controls, level of IL-2 increased significantly, while IL-10 decreased significantly (P hypercholesterolemia. © 2016 Wiley Periodicals, Inc.

  7. IL22/IL-22R pathway induces cell survival in human glioblastoma cells.

    Directory of Open Access Journals (Sweden)

    Hussein Akil

    Full Text Available Interleukin-22 (IL-22 is a member of the IL-10 cytokine family that binds to a heterodimeric receptor consisting of IL-22 receptor 1 (IL-22R1 and IL-10R2. IL-22R expression was initially characterized on epithelial cells, and plays an essential role in a number of inflammatory diseases. Recently, a functional receptor was detected on cancer cells such as hepatocarcinoma and lung carcinoma, but its presence was not reported in glioblastoma (GBM. Two GBM cell lines and 10 primary cell lines established from patients undergoing surgery for malignant GBM were used to investigate the expression of IL-22 and IL-22R by using quantitative RT-PCR, western blotting and confocal microscopy studies. The role of IL-22 in proliferation and survival of GBM cell lines was investigated in vitro by BrdU and ELISA cell death assays. We report herein that the two subunits of the IL-22R complex are expressed on human GBM cells. Their activation, depending on exogenous IL-22, induced antiapoptotic effect and cell proliferation. IL-22 treatment of GBM cells resulted in increased levels of phosphorylated Akt, STAT3 signaling protein and its downstream antiapoptotic protein Bcl-xL and decreased level of phosphorylated ERK1/2. In addition, IL-22R subunits were expressed in all the 10 tested primary cell lines established from GBM tumors. Our results showed that IL-22R is expressed on GBM established and primary cell lines. Depending on STAT3, ERK1/2 and PI3K/Akt pathways, IL-22 induced GBM cell survival. These data are consistent with a potential role of IL-22R in tumorigenesis of GBM. Since endogenous IL-22 was not detected in all studied GBM cells, we hypothesize that IL-22R could be activated by immune microenvironmental IL-22 producing cells.

  8. Unchanged Levels of Soluble CD14 and IL-6 Over Time Predict Serious Non-AIDS Events in HIV-1-Infected People

    Science.gov (United States)

    Sunil, Meena; Nigalye, Maitreyee; Somasunderam, Anoma; Martinez, Maria Laura; Yu, Xiaoying; Arduino, Roberto C.; Bell, Tanvir K.

    2016-01-01

    Abstract HIV-1-infected persons have increased risk of serious non-AIDS events (SNAEs) despite suppressive antiretroviral therapy. Increased circulating levels of soluble CD14 (sCD14), soluble CD163 (sCD163), and interleukin-6 (IL-6) at a single time point have been associated with SNAEs. However, whether changes in these biomarker levels predict SNAEs in HIV-1-infected persons is unknown. We hypothesized that greater decreases in inflammatory biomarkers would be associated with fewer SNAEs. We identified 39 patients with SNAEs, including major cardiovascular events, end stage renal disease, decompensated cirrhosis, non-AIDS-defining malignancies, and death of unknown cause, and age- and sex-matched HIV-1-infected controls. sCD14, sCD163, and IL-6 were measured at study enrollment (T1) and proximal to the event (T2) or equivalent duration in matched controls. Over ∼34 months, unchanged rather than decreasing levels of sCD14 and IL-6 predicted SNAEs. Older age and current illicit substance abuse, but not HCV coinfection, were associated with SNAEs. In a multivariate analysis, older age, illicit substance use, and unchanged IL-6 levels remained significantly associated with SNAEs. Thus, the trajectories of sCD14 and IL-6 levels predict SNAEs. Interventions to decrease illicit substance use may decrease the risk of SNAEs in HIV-1-infected persons. PMID:27344921

  9. Fasting induces IL-1 resistance and free fatty acid-mediated up-regulation of IL-1R2 and IL-1RA

    Directory of Open Access Journals (Sweden)

    jenifer j joesting

    2014-07-01

    Full Text Available Objective: Weight loss is a near societal obsession and many diet programs use significant calorie restriction (CR including fasting/short term starvation to generate rapid effects. Fasting is also a well-recognized cause of immunosuppression especially within the innate immune system. In this study, we sought to determine if the IL-1 arm of the neuroimmune system was down-regulated by a 24 hr fast and how fasting might generate this effect. Design: Mice were allowed ad libitum access to food or had food withheld for 24 hrs. Expression of the endogenous IL-1 antagonists IL-1 receptor type 2 (IL-1R2 and IL-1 receptor antagonist (IL-1RA were determined as were sickness behaviors before and after IL-1 administration.Results: Fasting markedly increased gene expression of IL-1R2 (83-fold in adipose tissue, 9.5-fold in liver and IL-1RA (68-fold in liver. Fasted mice were protected from IL-1-induced weight loss, hypoglycemia, loss of locomotor and social anxiety. These protections were coupled to a large positive interaction of fasting and IL-1 on IL-1R2 gene expression in adipose tissue and liver (2.6-fold and 1.6-fold, respectively. Fasting not only increased IL-1RA and IL-1R2 protein 2.5-fold and 3.2-fold, respectively, in liver; but also increased IL-1R2 1.8-fold in adipose tissue. Fasting, in turn, triggered a 2.4-fold increase in plasma free-fatty acids (FFAs and a 2.1-fold increase in plasma corticosterone. Inhibition, of glucocorticoid action with mifepristone did not impact fasting-dependent IL-1R2 or IL-1RA gene expression. Administration of the FFA, palmitate, to mice increased liver IL-1R2 and IL-1RA gene expression by 14-fold and 11-fold, respectively. Conclusion: These findings indicate that fasting augments expression of endogenous IL-1 antagonists inducing IL-1 resistance. Fasting-induced increases in plasma FFAs appears to be a signal that drives immunosuppression during fasting/short term starvation.

  10. Clinical significance of measurement of changes of serum IL-2, SIL-2R levels, B lymphocyte number and T-cell subsets after chemotherapy in patients with malignant hydatidiform mole

    International Nuclear Information System (INIS)

    Zhang Guangcai

    2007-01-01

    Objective: To study the clinical significance of changes of serum IL-2, SIL-2R level, peripheral blood B lymphocyte number and T-cell subsets after chemotherapy in patients with malignant hydatidiform mole. Methods: Serum IL-2 ( with RIA), SIL-2R level (with ELISA) and peripheral blood B lymphocytes number as well as T subsets (with monoclonal antibody technique) were measured both before and after chemotherapy in 32 patients with malignant hydatidiform mole as well as in 35 controls. Results: Before chemotherapy serum SIL-2R level and B lymphocyte were significantly higher in the patients than those in controls (P<0.01), while the serum IL-2 level, CD3, CD4, CD4/CD8 were significantly lower (P<0.01). Six months after chemotherapy the levels changed markedly toward normal, but remained significantly different from those in controls (P<0.05). Conclusion: Abnormal immuno-regulation were present in patients with malignant mole. (authors)

  11. Structure and Mechanism of Receptoe Sharing by the IL-10R2 Common Chain

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Sung-il; Jones, Brandi C.; Logsdon, Naomi J.; Harris, Bethany D.; Deshpande, Ashlesha; Radaeva, Svetlana; Halloran, Brian A.; Gao, Bin; Walter, Mark R. (NIH); (UAB)

    2010-06-14

    IL-10R2 is a shared cell surface receptor required for the activation of five class 2 cytokines (IL-10, IL-22, IL-26, IL-28, and IL-29) that play critical roles in host defense. To define the molecular mechanisms that regulate its promiscuous binding, we have determined the crystal structure of the IL-10R2 ectodomain at 2.14 {angstrom} resolution. IL-10R2 residues required for binding were identified by alanine scanning and used to derive computational models of IL-10/IL-10R1/IL-10R2 and IL-22/IL-22R1/IL-10R2 ternary complexes. The models reveal a conserved binding epitope that is surrounded by two clefts that accommodate the structural and chemical diversity of the cytokines. These results provide a structural framework for interpreting IL-10R2 single nucleotide polymorphisms associated with human disease.

  12. Structure and Mechanism of Receptor Sharing by the IL-10R2 Common Chain

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Sung-il; Jones, Brandi C.; Logsdon, Naomi J.; Harris, Bethany D.; Deshpande, Ashlesha; Radaeva, Svetlana; Halloran, Brian A.; Gao, Bin; Walter, Mark R. (NIH); (UAB)

    2010-07-19

    IL-10R2 is a shared cell surface receptor required for the activation of five class 2 cytokines (IL-10, IL-22, IL-26, IL-28, and IL-29) that play critical roles in host defense. To define the molecular mechanisms that regulate its promiscuous binding, we have determined the crystal structure of the IL-10R2 ectodomain at 2.14 {angstrom} resolution. IL-10R2 residues required for binding were identified by alanine scanning and used to derive computational models of IL-10/IL-10R1/IL-10R2 and IL-22/IL-22R1/IL-10R2 ternary complexes. The models reveal a conserved binding epitope that is surrounded by two clefts that accommodate the structural and chemical diversity of the cytokines. These results provide a structural framework for interpreting IL-10R2 single nucleotide polymorphisms associated with human disease.

  13. TH1/TH2 cytokines and soluble CD30 levels in kidney allograft patients with donor bone marrow cell infusion.

    Science.gov (United States)

    Solgi, G; Amirzagar, A A; Pourmand, G; Mehrsai, A R; Taherimahmoudi, M; Baradaran, N; Nicknam, M H; Ebrahimi Rad, M R; Saraji, A; Asadpoor, A A; Moheiydin, M; Nikbin, B

    2009-09-01

    We investigated the relevance of donor bone marrow cell infusion (DBMI) and serum levels of interferon-gamma (IFN-gamma), interleukin-10 (IL-10), and soluble CD30 (sCD30) in kidney recipients. We analyzed the allograft outcomes correlated with sCD30, IFN-gamma, and IL-10 levels using pre- and posttransplantation sera from 40 live donor renal transplants (20 patients with DBMI [2.1 x 10(9) +/- 1.3 x 10(9) mononuclear cells/body] and 20 controls). Patients with acute rejection episodes (ARE)-3/20 DBMI and 6/20 controls-showed increased sCD30 and IFN-gamma as well as decreased IL-10 posttransplantation compared with nonrejectors. Significant differences were observed for sCD30 and IFN-gamma levels: 59.54 vs 30.92 ng/mL (P = .02) and 11.91 vs 3.01 pg/mL (P = .01), respectively. Comparison of pre- and posttransplant levels of IFN-gamma, IL-10, and sCD30 in ARE patients showed higher levels in posttransplant sera except for IFN-gamma in controls (6.37 vs 11.93; P = .01). Increased IFN-gamma and IL-10 were correlated with rejection (r = .93; P = .008). sCD30 correlated with serum creatinine among ARE patients in control and DBMI groups (r = .89; P = .019; and r = 1.00; P sCD30, IFN-gamma, and IL-10 posttransplantation in rejecting patients provided evidence for coexistence of cellular and humoral responses in ARE. There appeared to be a down-regulatory effect of infusion on alloresponses.

  14. Higher proliferation of peritumoral endothelial cells to IL-6/sIL-6R than tumoral endothelial cells in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Zhuang, Peng-Yuan; Wang, Jian-Dong; Tang, Zhao-Hui; Zhou, Xue-Ping; Quan, Zhi-Wei; Liu, Ying-Bin; Shen, Jun

    2015-01-01

    This study aimed to explore the responses to the interleukin-6 (IL-6)/soluble interleukin-6 receptor (sIL-6R) complex in peritumoral endothelial cells (PECs) and tumor endothelial cells (TECs), as well as determine the signaling pathways in the angiogenesis of hepatocellular carcinoma (HCC). The expression of IL-6, IL-6R, gp130, CD68, HIF-1α, and microvessel density (MVD) were assessed with an orthotopic xenograft model in nude mice. ECs were incubated under hypoxic conditions to detect IL-6 and gp130. The proliferation of PECs and TECs in the presence of IL-6 and sIL-6R, as well as the expression of gp130, JAK2/STAT3, PI3K/AKT in endothelial cells were measured. Peritumoral IL-6, IL-6R, gp130, CD68, and HIF-1α expression, as well as MVD, gradually increased during tumor growth. Hypoxia could directly induce IL-6 expression, but not gp130 in PECs. The co-culture of IL-6/sIL-6R induced much higher PEC proliferation and gp130 expression, as well as the elevated phosphorylation of JAK2 and STAT3, however not the phosphorylation of PI3K and AKT. PECs exhibited higher proliferation in response to IL-6/sIL-6R co-treatment compared with TECs in HCC via the up-regulation of gp130 /JAK2/STAT3. PEC and its associated peritumoral angiogenesis microenvironment may be a potential novel target for anti-angiogenic treatment. The online version of this article (doi:10.1186/s12885-015-1763-2) contains supplementary material, which is available to authorized users

  15. Clinical significance of determination of serum IL-2, IL-6 and GM-CSF levels after treatment in pediatric patients with bronchial asthma

    International Nuclear Information System (INIS)

    Wang Zhuo; Sun Jin; Yao Li

    2009-01-01

    Objective: To explore the clinical significance of changes of serum IL-2, IL-6 and GM-CSF levels after treatment in pediatric patients with bronchial asthma. Methods: Serum levels of IL-2, IL-6 and GM-CSF were measured with RIA in 36 pediatric patients with bronchiol asthma and 30 controls. Results: Before treatment, the serum levels of IL-6, GM-CSF were significantly higher in the patients than those in controls (P 0.05), Serum IL-2 levels were negatively correlated with the IL-6 and GM-CSF levels (r=-0.5846, -0.6018, P<0.01). Conclusion: These cytokines participated in the pathogenesis of bronchial asthma in pediatric patients. Mornitoring the changes of their serum levels was helpful for the management of the diseases. (authors)

  16. Clinical significance of measurement of changes of serum IL-2, SIL-2R, TNF-α levels, B lymphocyte count and T subsets distribution type after treatment in patients with vitiligo

    International Nuclear Information System (INIS)

    Xie Chuntao

    2007-01-01

    Objective: To study the changes of serum IL-2, SIL-2R, TNF-α levels B lymphocytes count and T lyonphocyte subsets distribation type after treatment in patients with vitiligo. Methods: Serum IL-2, TNF-α (with RIA), SIL-2R (with ELISA) levels, B lymphocytes count and T subsets (with monoclonal antibody technique) were examined in 40 patients with vitiligo both before and after treatment as well as in 35 controls. Results: Before treatment, serum SIL-2R, TNF-α levels and B lymphocytes count were significantly higher than those in controls (P<0.01), while the serum IL-2, CD3, CD4 levels CD4/CD8 ratio were significantly lower(P<0.01). After treatment for 6 months, the data were greatly corrected but remanied significantly different from those in controls (P<0.05). Conclusion: Vitiligo is a kind of auto-immune diseases with abnormal immuno-regulation. (authors)

  17. Serum Levels of Interleukin 33 and Soluble ST2 Are Associated with the Extent of Disease Activity and Cutaneous Manifestations in Patients with Active Adult-onset Still's Disease.

    Science.gov (United States)

    Han, Jae Ho; Suh, Chang-Hee; Jung, Ju-Yang; Ahn, Mi-Hyun; Kwon, Ji Eun; Yim, Hyunee; Kim, Hyoun-Ah

    2017-06-01

    Interleukin 33 (IL-33), a member of the IL-1 family and a ligand of the orphan receptor ST2, plays key roles in innate and adaptive immunity. We examined the associations between IL-33/ST2 levels and clinical manifestations of patients with active adult-onset Still's disease (AOSD). Blood samples were collected from 40 patients with active AOSD, 28 patients with rheumatoid arthritis (RA), and 27 healthy controls (HC). The serum levels of IL-33 and soluble ST2 were determined using ELISA. Expression levels of IL-33 and ST2 in biopsy specimens obtained from 34 AOSD patients with rash were immunohistochemically investigated. IL-33 levels of patients with AOSD were higher than those of patients with RA and HC. Soluble ST2 levels of patients with AOSD were higher than those of HC, but not of patients with RA. Serum IL-33 levels correlated with systemic score, erythrocyte sedimentation rate, ferritin levels, and aspartate transaminase levels. However, serum soluble ST2 levels correlated only with ferritin levels. The numbers of inflammatory cells expressing IL-33 and ST2 were elevated in skin lesions of patients with AOSD compared to HC, but did not differ from those of the skin lesions of eczema or psoriasis. We found significantly higher serum IL-33 and soluble ST2 levels in patients with active AOSD. Results indicate that the IL-33/ST2 signaling pathway may play a role in the pathogenesis of the acute inflammation and skin manifestations associated with AOSD.

  18. Association study of IL10 and IL23R-IL12RB2 in Iranian patients with Behçet's disease.

    Science.gov (United States)

    Xavier, Joana M; Shahram, Farhad; Davatchi, Fereydoun; Rosa, Alexandra; Crespo, Jorge; Abdollahi, Bahar Sadeghi; Nadji, Abdolhadi; Jesus, Gorete; Barcelos, Filipe; Patto, José Vaz; Shafiee, Niloofar Mojarad; Ghaderibarim, Fahmida; Oliveira, Sofia A

    2012-08-01

    Independent replication of the findings from genome-wide association studies (GWAS) remains the gold standard for results validation. Our aim was to test the association of Behçet's disease (BD) with the interleukin-10 gene (IL10) and the IL-23 receptor-IL-12 receptor β2 (IL23R-IL12RB2) locus, each of which has been previously identified as a risk factor for BD in 2 different GWAS. Six haplotype-tagging single-nucleotide polymorphisms (SNPs) in IL10 and 42 in IL23R-IL12RB2 were genotyped in 973 Iranian patients with BD and 637 non-BD controls. Population stratification was assessed using a panel of 86 ancestry-informative markers. Subtle evidence of population stratification was found in our data set. In IL10, rs1518111 was nominally associated with BD before and after adjustment for population stratification (odds ratio [OR] for T allele 1.20, 95% confidence interval [95% CI] 1.02-1.40, unadjusted P [P(unadj) ] = 2.53 × 10(-2) ; adjusted P [P(adj) ] = 1.43 × 10(-2) ), and rs1554286 demonstrated a trend toward association (P(unadj) = 6.14 × 10(-2) ; P(adj) = 3.21 × 10(-2) ). Six SNPs in IL23R-IL12RB2 were found to be associated with BD after Bonferroni correction for multiple testing, the most significant of which were rs17375018 (OR for G allele 1.51, 95% CI 1.27-1.78, P(unadj) = 1.93 × 10(-6) ), rs7517847 (OR for T allele 1.48, 95% CI 1.26-1.74, P(unadj) = 1.23 × 10(-6) ), and rs924080 (OR for T allele 1.29, 95% CI 1.20-1.39, P = 1.78 × 10(-5) ). SNPs rs10489629, rs1343151, and rs1495965 were also significantly associated with BD in all tests performed. Results of meta-analyses of our data combined with data from other populations further confirmed the role of rs1518111, rs17375018, rs7517847, and rs924080 in the risk of BD, but no epistatic interactions between IL10 and IL23R-IL12RB2 were detected. Results of imputation analysis highlighted the importance of IL23R regulatory regions in the susceptibility to BD. These findings independently confirm

  19. Serum soluble ST2 is associated with ER-positive breast cancer

    International Nuclear Information System (INIS)

    Lu, Da-peng; Zhou, Xiang-yu; Yao, Lu-tian; Liu, Cai-gang; Ma, Wei; Jin, Feng; Wu, Yun-fei

    2014-01-01

    ST2, a member of the interleukin (IL)-1receptor family, regulates Th1/Th2 immune responses in autoimmune and inflammatory conditions. However, the role of ST2 signaling in tumor growth and metastasis of breast cancers has not been investigated. This study investigated the possible role of soluble ST2 (sST2) in breast cancer. The serum levels of IL-33, sST2, and vascular endothelial growth factor (VEGF) in 150 breast cancer patients and 90 healthy women were measured by enzyme-linked immunosorbent assay. Estrogen receptor(ER), progesterone receptor, human epithelial receptor (HER)-2, and cell cycle regulated protein Ki-67 were measured. Clinical stage, tumor size, lymph node metastasis, and histological type were also recorded. The serum levels of sST2, IL-33, and VEGF were significantly higher in breast cancer patients than in the control group (P < 0.05, each). Serum sST2 levels in ER-positive breast cancer patients were significantly associated with age, histological type, clinical stage, tumor size, and Ki-67 status (P < 0.05, each). Moreover, the serum levels of IL-33 and sST2 in breast cancers significantly correlated with VEGF levels (IL-33: r = 0.375, P < 0.0001; sST2: r = 0.164, P = 0.045). Serum levels of sST2, IL-33, and VEGF decreased after modified radical mastectomy in ER-positive breast cancers. Serum levels of IL-33, sST2, and VEGF and clinicopathological factors were not significantly correlated with disease-free survival and overall survival of ER-positive breast cancer women during follow-up. Serum sST2 levels in ER-positive breast cancer patients are significantly associated with factors that indicate poor prognosis

  20. IL6R Variation Asp358Ala Is a Potential Modifier of Lung Function in Asthma

    Science.gov (United States)

    Hawkins, Gregory A; Robinson, Mac B; Hastie, Annette T; Li, Xingnan; Li, Huashi; Moore, Wendy C; Howard, Timothy D; Busse, William W.; Erzurum, Serpil C.; Wenzel, Sally E.; Peters, Stephen P; Meyers, Deborah A; Bleecker, Eugene R

    2012-01-01

    Background The IL6R SNP rs4129267 has recently been identified as an asthma susceptibility locus in subjects of European ancestry but has not been characterized with respect to asthma severity. The SNP rs4129267 is in linkage disequilibrium (r2=1) with the IL6R coding SNP rs2228145 (Asp358Ala). This IL6R coding change increases IL6 receptor shedding and promotes IL6 transsignaling. Objectives To evaluate the IL6R SNP rs2228145 with respect to asthma severity phenotypes. Methods The IL6R SNP rs2228145 was evaluated in subjects of European ancestry with asthma from the Severe Asthma Research Program (SARP). Lung function associations were replicated in the Collaborative Study on the Genetics of Asthma (CSGA) cohort. Serum soluble IL6 receptor (sIL6R) levels were measured in subjects from SARP. Immunohistochemistry was used to qualitatively evaluate IL6R protein expression in BAL cells and endobronchial biopsies. Results The minor C allele of IL6R SNP rs2228145 was associated with lower ppFEV1 in the SARP cohort (p=0.005), the CSGA cohort (0.008), and in combined cohort analysis (p=0.003). Additional associations with ppFVC, FEV1/FVC, and PC20 were observed. The rs2228145 C allele (Ala358) was more frequent in severe asthma phenotypic clusters. Elevated serum sIL6R was associated with lower ppFEV1 (p=0.02) and lower ppFVC (p=0.008) (N=146). IL6R protein expression was observed in BAL macrophages, airway epithelium, vascular endothelium, and airway smooth muscle. Conclusions The IL6R coding SNP rs2228145 (Asp358Ala) is a potential modifier of lung function in asthma and may identify subjects at risk for more severe asthma. IL6 transsignaling may have a pathogenic role in the lung. PMID:22554704

  1. Clinical evaluation of determination the changes on serum IL-2, IL-4 and IFN-γ levels after treatment in pediatric patients with acute nephritis

    International Nuclear Information System (INIS)

    Zhou Hong; Hu Yan; Wei Guoyu; Liu Ya

    2011-01-01

    Objective: To explore the clinical evaluation of the changes of determination of serum IL-2, IL-4 and IFN-γ levels after treatment in pediatric patients with acute nephritis. Methods: Serum IL-2 (with RIA), IL-4, IFN-γ (with ELISA) levels were determined both before and after treatment in 32 pediatric patients with acute nephritis and 35 normal controls. Results: The serum IL-4, IFN-γ levels were significantly higher in the patients than those in controls before treatment (P 0.05). Serum IL-2 levels were negatively correlated with IL-4, IFN-γ levels (r=-0.5536, -0.6012, P<0.01). Conclusion: Interaction of the serum IL-2, IL-4 and IFN-γ also participated in the pathogenesis of acute nephritis in pediatric patients, monitoring the changes of their serum levels was helpful for the management of the diseases and provider important clinical value. (authors)

  2. [Soluble interleukin 2 receptor as activity parameter in serum of systemic and discoid lupus erythematosus].

    Science.gov (United States)

    Blum, C; Zillikens, D; Tony, H P; Hartmann, A A; Burg, G

    1993-05-01

    The evaluation of disease activity in systemic lupus erythematosus (SLE) is important for selection of the appropriate therapeutic regimen. In addition to the clinical picture, various laboratory parameters are taken into account. However, no validated criteria for the evaluation of the disease activity in SLE have yet been established. Recently, serum levels of soluble interleukin-2 receptor (sIL-2R) have been proposed as a potential parameter for disease activity in SLE. However, the studies reported on this subject so far have focused mainly on certain subsets of the disease, and the evaluation of the disease activity was based on a very limited number of parameters. In the present study, we determined serum levels of sIL-2R in 23 patients with SLE and 30 patients with discoid LE (DLE). Evaluation of disease activity in SLE was based on a comprehensive scale which considered numerous clinical signs and laboratory parameters. In SLE, serum levels of sIL-2R showed a better correlation with disease activity than all the other parameters investigated, including proteinuria, erythrocyte sedimentation rate, serum globulin concentration, titre of antibodies against double-stranded DNA, serum albumin concentration, serum complement levels and white blood cell count. For the first time, we report on elevated serum levels of sIL-2R in DLE, which also correlated with disease activity.

  3. Nuclear IL-33 regulates soluble ST2 receptor and IL-6 expression in primary human arterial endothelial cells and is decreased in idiopathic pulmonary arterial hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Shao, Dongmin [Section of Vascular Biology, National Heart and Lung Institute, Imperial College London, London (United Kingdom); Perros, Frédéric [Faculté de Médecine, Université Paris-Sud, Paris, Clamart (France); Caramori, Gaetano [Dipartimento di Scienze Mediche, Sezione di Medicina Interna e Cardiorespiratoria, Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-Correlate, University of Ferrara, Ferrara (Italy); Meng, Chao [Section of Vascular Biology, National Heart and Lung Institute, Imperial College London, London (United Kingdom); Department of Geriatrics, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai (China); Dormuller, Peter [Faculté de Médecine, Université Paris-Sud, Paris, Clamart (France); Chou, Pai-Chien [Airways Disease, National Heart and Lung Institute (United Kingdom); Church, Colin [Scottish Pulmonary Vascular Unit, University of Glasgow (United Kingdom); Papi, Alberto; Casolari, Paolo [Dipartimento di Scienze Mediche, Sezione di Medicina Interna e Cardiorespiratoria, Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-Correlate, University of Ferrara, Ferrara (Italy); Welsh, David; Peacock, Andrew [Scottish Pulmonary Vascular Unit, University of Glasgow (United Kingdom); Humbert, Marc [Faculté de Médecine, Université Paris-Sud, Paris, Clamart (France); Adcock, Ian M. [Airways Disease, National Heart and Lung Institute (United Kingdom); Wort, Stephen J., E-mail: s.wort@imperial.ac.uk [Section of Vascular Biology, National Heart and Lung Institute, Imperial College London, London (United Kingdom)

    2014-08-15

    Highlights: • Nuclear IL-33 expression is reduced in vascular endothelial cells from PAH patients. • Knockdown of IL-33 leads to increased IL-6 and sST2 mRNA expression. • IL-33 binds homeobox motifs in target gene promoters and recruits repressor proteins. - Abstract: Idiopathic pulmonary arterial hypertension (IPAH) is an incurable condition leading to right ventricular failure and death and inflammation is postulated to be associated with vascular remodelling. Interleukin (IL)-33, a member of the “alarmin” family can either act on the membrane ST2 receptor or as a nuclear repressor, to regulate inflammation. We show, using immunohistochemistry, that IL-33 expression is nuclear in the vessels of healthy subjects whereas nuclear IL-33 is markedly diminished in the vessels of IPAH patients. This correlates with reduced IL-33 mRNA expression in their lung. In contrast, serum levels of IL-33 are unchanged in IPAH. However, the expression of the soluble form of ST2, sST2, is enhanced in the serum of IPAH patients. Knock-down of IL-33 in human endothelial cells (ECs) using siRNA is associated with selective modulation of inflammatory genes involved in vascular remodelling including IL-6. Additionally, IL-33 knock-down significantly increased sST2 release from ECs. Chromatin immunoprecipitation demonstrated that IL-33 bound multiple putative homeodomain protein binding motifs in the proximal and distal promoters of ST2 genes. IL-33 formed a complex with the histone methyltransferase SUV39H1, a transcriptional repressor. In conclusion, IL-33 regulates the expression of IL-6 and sST2, an endogenous IL-33 inhibitor, in primary human ECs and may play an important role in the pathogenesis of PAH through recruitment of transcriptional repressor proteins.

  4. Clinical significance of determination of changes of serum IL-2, SIL-2R, TNF-α contents and T-cell subgroup distribution type in patients with psoriasis

    International Nuclear Information System (INIS)

    Mou Xudong

    2005-01-01

    Objective: To investigate the changes of serum IL-2, SIL-2R, TNF-α contents and T-cell subgroup distribution type in patients with psoriasis. Methods: Serum IL-2 and TNF-α levels were measured with RIA, SIL-2R levels was measured with ELISA and T-cell subgroup distribution type was detected with monoclonal antibody in 40 patients with psoriasis and 35 controls. Results: The serum IL-2 levels and CD 4 /CD 8 values were significantly lower in the patients than those in controls (P<0.01), while the serum SIL-2R, TNF-α levels were significantly higher (P<0.01). Conclusion: Determination of serum IL-2, SIL-2R, TNF-α contents and T-cell subgroup distribution type is clinically useful for understanding the disturbances of immuno-modulation in these patients. (authors)

  5. Toll/Interleukin-1 receptor member ST2 exhibits higher soluble levels in type 2 diabetes, especially when accompanied with left ventricular diastolic dysfunction

    Directory of Open Access Journals (Sweden)

    Fousteris Evangelos

    2011-11-01

    Full Text Available Abstract Background Soluble ST2, a member of the of the Toll/IL-1 superfamily, is a novel biomarker with exceptional predictive value in heart failure and myocardial infarction- related mortality as well as in acute dyspneic states. Soluble ST2 is considered a decoy receptor of IL 33 that blocks the protective effects of the cytokine in atherosclerosis and cardiac remodeling. In the present study we investigated the differences in the levels of soluble ST2, BNP and hs-CRP between healthy controls and patients with type 2 diabetes with and without left ventricular diastolic dysfunction. A secondary aim was to investigate correlations between sST2 and other biomarkers of type 2 diabetes, such as HbA1c. Methods 158 volunteers were recruited and underwent a complete Doppler-echocardiographic evaluation of both systolic & diastolic cardiac function. All subjects with ejection fraction Results Patients with type 2 diabetes with (p Conclusions Patients with type 2 diabetes exhibit higher sST2 levels compared to healthy controls. The presence of LVDD in patients with type 2 diabetes is associated with even higher sST2 levels. A significant correlation between glycemic control and sST2 levels was also revealed.

  6. Study on the changes of serum IL-2, IL-6, IL-8 and TNF levels in patients with diabetic nephrosis

    International Nuclear Information System (INIS)

    Qin Wenjing

    2005-01-01

    Objective: To investigate the changes of serum IL-2, IL-6, IL-8 and TNF levels in patients with diabetic nephrosis. Methods: Serum IL-2, IL-6, IL-8 and TNF levels were measured with RIA in 38 patients with diabetic nephrosis and 36 controls. Results: Serum levels of IL-6, IL-8 and TNF were significantly higher in patients with diabetic nephrosis than those in controls (P<0.01), but serum IL-2 levels were significantly lower in the patients (P<0.01). Conclusion: These cytokines participated in the pathogenesis of diabetic nephrosis. Monitoring the changes of their serum levels was helpful for the management of the disease. (authors)

  7. Polymorphisms of ST2-IL18R1-IL18RAP gene cluster: a new risk for autoimmune thyroid diseases.

    Science.gov (United States)

    Wang, X; Zhu, Y F; Li, D M; Qin, Q; Wang, Q; Muhali, F S; Jiang, W J; Zhang, J A

    2016-02-01

    Interleukin 33 (IL33) / ST2 pathway and ST2-interlukin18 receptor1-interlukin18 receptor accessory protein (ST2-IL18R1-IL18RAP) gene cluster have been involved in many autoimmune diseases but few report in autoimmune thyroid diseases (AITD). In this study, we investigated whether polymorphisms of IL33, ST2, IL18R1, and IL18RAP are associated with Graves' disease (GD) and Hashimoto's thyroiditis (HT), two major forms of AITD, among a Chinese population. A total of 11 SNPs were explored in a case-control study including 417 patients with GD, 250 HT patients and 301 controls, including rs1929992, rs10975519, rs10208293, rs6543116, rs1041973, rs3732127, rs11465597, rs1035130, rs2293225, rs1035127, rs917997 of IL 33, ST2-IL18R1-IL18RAP gene cluster. Genotyping of these SNPs was performed using matrix-assisted laser desorption / ionization-time-of-flight mass spectrometer (MALDI-TOF-MS) platform from Sequenom. The frequencies of allele A and AA+AG genotype of rs6543116 (ST2) in HT patients were significantly increased compared with those of the controls (P = 0.029/0.021, OR = 1.31/1.62). And in another SNP rs917997, AA+AG genotype presented an increased frequency in HT subjects compared with controls (P = 0.046, OR = 1.53). Furthermore, the haplotype GAGCCCG from ST2-IL18R1-IL18RAP gene cluster (rs6543116, rs1041973, rs1035130, rs3732127, rs1035127, rs2293225, rs917997) was associated with increased susceptibility to GD with an OR of 2.03 (P = 0.022, 95% CI = 1.07-3.86). Some SNPs of ST2-IL18R1-IL18RAP gene cluster might increase the risk of susceptibility of HT and GD in Chinese Han population. © 2015 John Wiley & Sons Ltd.

  8. Clinical significance of changes of levels of serum IL-2, IL-8, IL-10 and gastrin in patients with chronic eczema

    International Nuclear Information System (INIS)

    Huang Haifeng; Bi Mingye; Shi Hejian

    2009-01-01

    Objective: To study the significance of changes of serum IL-2, IL-8, IL-10 and Gastrin levels in patients with chronic eczema. Methods: Serum levels of IL-2, IL-8, IL-10 and Gastrin were determined with RIA in 30 patients with chronic eczema and 30 controls. Results: The levels of serum IL-2 were significantly lower in the eczema patients than those in controls (P 0.05). Both serum IL-10 and Gastrin levels were significantly higher in the patients than those in controls (P<0.01). Conclusion: Determination of serum IL-2, IL-8, IL-10 and Gastrin levels in patients with chronic eczema would be of help in monitoring the disease process and outcome prediction. (authors)

  9. Cytokines and soluble adhesion molecules in children and adolescents with a tic disorder.

    Science.gov (United States)

    Bos-Veneman, Netty G P; Bijzet, Johan; Limburg, Pieter C; Minderaa, Ruud B; Kallenberg, Cees G; Hoekstra, Pieter J

    2010-12-01

    Dysregulation of the immune system may play a role in tic disorders. We screened for immune disturbances by investigating serum levels of cytokines and soluble adhesion molecules in patients with a tic disorder. Serum levels of interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12, soluble IL-2 receptor (sIL2R), tumor necrosis factor (TNF)-α, interferon (IFN)-γ, soluble vascular cell adhesion molecule-1 (sVCAM-1), and intercellular adhesion molecule-1 (sICAM-1) of 66 children and adolescents with a tic disorder and 71 healthy volunteers were compared. We also addressed possible relations between concentrations of the immune markers and severity of tics and comorbid obsessive-compulsive symptoms. Median serum concentrations did not differ significantly between patients and healthy subjects. Serum IL-2 concentrations were positively associated with tic severity ratings; serum IL-12 concentrations negatively with severity ratings of obsessive-compulsive symptoms. These preliminary findings do not reveal major immune activation in children with a tic disorder but may suggest more subtle disturbances related to disease expression. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Soluble Interleukin-7 receptor levels and risk of acute graft-versus-disease after allogeneic haematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Kielsen, Katrine; Shamim, Zaiba; Thiant, Stephanie

    2018-01-01

    Interleukin-7 is a cytokine essential for T cell homeostasis. IL-7 binds to cellular IL-7 receptors in competition with a soluble form of the receptor (sIL-7Rα). We hypothesized that altered sIL-7Rα levels may cause adverse outcomes in patients undergoing HSCT. In parallel, we investigated...... the impact of the IL-7Rα SNP rs6897932, which has been associated with release of IL-7R.The sIL-7Rα levels decreased during HSCT (from 114. ng/ml before to 48. ng/ml at day +. 14 (P sIL-7Rα ratio at day +. 14 was significantly higher...... in patients developing grade II-IV aGVHD (OR = 4.3, P = 0.026). Furthermore, donor carriage of the rs6897932 T allele was associated with reduced sIL-7Rα levels, increased risk of grades II-IV aGVHD (OR = 2.4, P = 0.055) and increased transplant-related mortality (CC = 4.5%, CT = 21.4% and TT = 27.3%, P = 0...

  11. Association analysis of IL10, TNF-α and IL23R-IL12RB2 SNPs with Behçet's disease risk in Western Algeria

    Directory of Open Access Journals (Sweden)

    Ouahiba eKhaib Dit Naib

    2013-10-01

    Full Text Available Objective: We have conducted the first study of the association of interleukin (IL-10, tumor necrosis factor alpha (TNF-α and IL23R-IL12RB2 regionSNPswith Behçet's disease (BD in Western Algeria. Methods: A total of 51 BD patients and 96 unrelated controls from West region of Algeria were genotyped by direct sequencing for 11 SNPs including 2 SNPsfrom the IL10 promoter [c.-819T>C (rs1800871, c.-592A>C (rs1800872], 6 SNPs from the TNF-α promoter [c.-1211T>C (rs1799964, c.-1043C>A (rs1800630, c.-1037C>T (rs1799724, c.-556G>A (rs1800750, c.-488G>A (rs1800629 and c.-418G>A (rs361525], and 3 SNPs from the IL23R-IL12RB2 region [g.67747415A>C (rs12119179, g.67740092G>A (rs11209032 and g.67760140T>C (rs924080]. Results: The minor alleles c.-819T and c.-592A were significantly associated with BD (OR= 2.18; 95% CI 1.28-3.73, p = 0.003; whereas, there was weaker association between TNF-αpromoter SNPs or IL23R-IL12RB2 region and disease risk.Conclusion: Unlike the TNF-αand the IL23R-IL12RB2 region SNPs, the two IL10 SNPs were strongly associated with BD. The -819T, and -592A alleles and the -819TT, -819CT, and -592AA and -592CA genotypes seem to be highly involved in the risk of developing of BD in the population of Western Algeria.

  12. The dichotomous pattern of IL-12r and IL-23R expression elucidates the role of IL-12 and IL-23 in inflammation.

    Directory of Open Access Journals (Sweden)

    Gaëlle Chognard

    Full Text Available IL-12 and IL-23 cytokines respectively drive Th1 and Th17 type responses. Yet, little is known regarding the biology of these receptors. As the IL-12 and IL-23 receptors share a common subunit, it has been assumed that these receptors are co-expressed. Surprisingly, we find that the expression of each of these receptors is restricted to specific cell types, in both mouse and human. Indeed, although IL-12Rβ2 is expressed by NK cells and a subset of γδ T cells, the expression of IL-23R is restricted to specific T cell subsets, a small number of B cells and innate lymphoid cells. By exploiting an IL-12- and IL-23-dependent mouse model of innate inflammation, we demonstrate an intricate interplay between IL-12Rβ2 NK cells and IL-23R innate lymphoid cells with respectively dominant roles in the regulation of systemic versus local inflammatory responses. Together, these findings support an unforeseen lineage-specific dichotomy in the in vivo role of both the IL-12 and IL-23 pathways in pathological inflammatory states, which may allow more accurate dissection of the roles of these receptors in chronic inflammatory diseases in humans.

  13. [Cytokines and malaria. A study of TNF-alpha, IL1-beta, IL6 and IL2R in 28 patients].

    Science.gov (United States)

    Nicolas, P; Hovette, P; Merouze, F; Touze, J E; Martet, G

    1994-01-01

    Authors have studied TNF alpha, IL1 bêta, IL6 and RIL2s in 28 malaria illness patients. Increased levels of TNF, IL1 bêta and RIL2s in serum, are observed on admission to hospital. These cytokine levels are decreased, eight days later, after patients are treated. In discussion, TNF levels as a prognosis component is evocated.

  14. Bronchoalveolar lavage analysis, gallium-67 lung scanning and soluble interleukin-2 receptor levels in asbestos exposure

    International Nuclear Information System (INIS)

    Delclos, G.L.; Flitcraft, D.G.; Brousseau, K.P.; Windsor, N.T.; Nelson, D.L.; Wilson, R.K.; Lawrence, E.C.

    1989-01-01

    This study examined different markers of lung immunologic and inflammatory responses to previous asbestos exposure. We performed bronchoalveolar lavage (BAL) and gallium-67 ( 67 Ga) lung scans and measured serum and BAL soluble interleukin-2 receptor (IL-2R) and angiotensin-converting enzyme (SACE) levels in 32 subjects with a history of significant asbestos exposure, 14 without (EXP) and 18 with (ASB) radiographic evidence of asbestosis. BAL analysis revealed increases in neutrophils in both ASB and EXP when compared to controls (P less than 0.01), which persisted after adjustment for smoking category. Although significant abnormalities of macrophage and total lymphocyte profiles were not found in the study population, lymphocyte subpopulation analysis revealed elevation of BAL T4/T8 ratios in the entire study group (ASB + EXP) when compared to controls (P less than 0.05), independent of smoking category. 67 Ga lung scan activity was increased in 56% of ASB and in 36% of EXP: no correlations between positive scans and different radiological and functional parameters could be found. There was no significant elevation of mean SACE, serum, or BAL IL-2R levels in any of the study categories. These data suggest that asbestos exposure may be associated with parenchymal inflammation, even in the absence of clinical criteria for asbestosis. Abnormalities of gallium uptake and of BAL analysis reflect the clinically inapparent inflammation. The increased BAL T4/T8 ratios observed suggest that abnormal local pulmonary immunoregulation may play a role in the pathogenesis of asbestos-related lung diseases

  15. Internalization of interleukin 1 (IL 1) correlates with IL 1-induced IL 2 receptor expression and IL 2 secretion of EL4 thymoma cells

    OpenAIRE

    Von Hoegen, I.; Falk, Werner; Kojouharoff, G.; Krammer, P. H.

    1989-01-01

    The cytokine interleukin 1 (IL 1) plays an important role in the induction of IL 2 secretion and high-affinity IL 2 receptor (IL 2R) expression by T cells. The events that follow binding of IL 1 to IL 1R, however, are still unknown. In this study we describe two variants of the murine thymoma EL4 (5D3 and D6/76) that express comparable numbers of cell surface IL 1 receptors and bind IL 1 with the same affinity, but show distinct IL 1-dependent IL 2 secretion and IL 2R expression. In the prese...

  16. Pretreatment with soluble ST2 reduces warm hepatic ischemia/reperfusion injury

    International Nuclear Information System (INIS)

    Yin Hui; Huang Baojun; Yang Heng; Huang Yafei; Xiong Ping; Zheng Fang; Chen Xiaoping; Chen Yifa; Gong Feili

    2006-01-01

    The interleukin-1 receptor-like protein ST2 exists in both membrane-bound (ST2L) and soluble form (sST2). ST2L has been found to play an important regulatory role in Th2-type immune response, but the function of soluble form of ST2 remains to be elucidated. In this study, we report the protective effect of soluble ST2 on warm hepatic ischemia/reperfusion injury. We constructed a eukaryotic expression plasmid, psST2-Fc, which expresses functional murine soluble ST2-human IgG1 Fc (sST2-Fc) fusion protein. The liver damage after ischemia/reperfusion was significantly attenuated by the expression of this plasmid in vivo. sST2-Fc remarkably inhibited the activation of Kupffer cells and the production of proinflammatory mediators TNF-α and IL-6. Furthermore, the levels of TLR4 mRNA and the nuclear translocation of NF-κB were also suppressed by pretreatment with sST2-Fc. These results thus identified soluble ST2 as a negative regulator in hepatic I/R injury, possibly via ST2-TLR4 pathway

  17. Curcumin blocks interleukin (IL)-2 signaling in T-lymphocytes by inhibiting IL-2 synthesis, CD25 expression, and IL-2 receptor signaling

    International Nuclear Information System (INIS)

    Forward, Nicholas A.; Conrad, David M.; Power Coombs, Melanie R.; Doucette, Carolyn D.; Furlong, Suzanne J.; Lin, Tong-Jun; Hoskin, David W.

    2011-01-01

    Highlights: → Curcumin inhibits CD4 + T-lymphocyte proliferation. → Curcumin inhibits interleukin-2 (IL-2) synthesis and CD25 expression by CD4 + T-lymphocytes. → Curcumin interferes with IL-2 receptor signaling by inhibiting JAK3 and STAT5 phosphorylation. → IL-2-dependent regulatory T-lymphocyte function and Foxp3 expression is downregulated by curcumin. -- Abstract: Curcumin (diferulomethane) is the principal curcuminoid in the spice tumeric and a potent inhibitor of activation-induced T-lymphocyte proliferation; however, the molecular basis of this immunosuppressive effect has not been well studied. Here we show that micromolar concentrations of curcumin inhibited DNA synthesis by mouse CD4 + T-lymphocytes, as well as interleukin-2 (IL-2) and CD25 (α chain of the high affinity IL-2 receptor) expression in response to antibody-mediated cross-linking of CD3 and CD28. Curcumin acted downstream of protein kinase C activation and intracellular Ca 2+ release to inhibit IκB phosphorylation, which is required for nuclear translocation of the transcription factor NFκB. In addition, IL-2-dependent DNA synthesis by mouse CTLL-2 cells, but not constitutive CD25 expression, was impaired in the presence of curcumin, which demonstrated an inhibitory effect on IL-2 receptor (IL-2R) signaling. IL-2-induced phosphorylation of STAT5A and JAK3, but not JAK1, was diminished in the presence of curcumin, indicating inhibition of critical proximal events in IL-2R signaling. In line with the inhibitory action of curcumin on IL-2R signaling, pretreatment of CD4 + CD25 + regulatory T-cells with curcumin downregulated suppressor function, as well as forkhead box p3 (Foxp3) expression. We conclude that curcumin inhibits IL-2 signaling by reducing available IL-2 and high affinity IL-2R, as well as interfering with IL-2R signaling.

  18. study on the serum levels of E2, IL-6 and IGF-I in patients with post-menopausal osteoporosis (PMO)

    International Nuclear Information System (INIS)

    Lv Kuan; Liu Chunyu; Lu Yingju

    2006-01-01

    Objective: To study the changes of serum levels of E 2 , IL-6, IGF-I in patients with post-menopausal osteoporosis (PMO). Methods: Serum levels of E 2 (with CLIA), IL-6, IGF-I, BGP (with RIA) were measured in the following subjects: (1) 32 patients with PMO (2) 32 post-menopausal women without PMO and (3) 30 pre-menopausal controls. Serum P, Ca and AKP levels were also determined. Results: As a whole, serum levels of IL -6 in postmenopausal women were higher than those in controls. Levels in subjects with PMO were significantly higher than those without PMO (P 2 and BMD index (r=-0. 587, - 0. 438 respectively, P 2 and BMD index (r=0.569, 0.433 respectively, P 2 levels will in someway promote the expression of IL-6 ( osteoclastic) and reduce the expression of IGF-I (osteoclastic), resulting in lessening of bone mass. HRT, despite of the controversy over cardio-vascalar safety, is beneficial for osteoporosis. (authors)

  19. The plasma levels of soluble ST2 as a marker of gut mucosal damage in early HIV infection

    Science.gov (United States)

    Mehraj, Vikram; Jenabian, Mohammad-Ali; Ponte, Rosalie; Lebouché, Bertrand; Costiniuk, Cecilia; Thomas, Réjean; Baril, Jean-Guy; LeBlanc, Roger; Cox, Joseph; Tremblay, Cécile; Routy, Jean-Pierre

    2016-01-01

    Objective: Following tissue barrier breaches, interleukin-33 (IL-33) is released as an ‘alarmin’ to induce inflammation. Soluble suppression of tumorigenicity 2 (sST2), as an IL-33 decoy receptor, contributes to limit inflammation. We assessed the relationship between the IL-33/ST2 axis and markers of gut mucosal damage in patients with early (EHI) and chronic HIV infection (CHI) and elite controllers. Design: Analyses on patients with EHI and CHI were conducted to determine IL-33/sST2 changes over time. Methods: IL-33 and sST2 levels were measured in plasma. Correlations between sST2 levels and plasma viral load, CD4+ and CD8+ T-cell counts, expression of T-cell activation/exhaustion markers, gut mucosal damage, microbial translocation and inflammation markers, as well as kynurenine/tryptophan ratio were assessed. Results: Plasma sST2 levels were elevated in EHI compared with untreated CHI and uninfected controls, whereas IL-33 levels were comparable in all groups. In EHI, sST2 levels were positively correlated with the CD8+ T-cell count and the percentage of T cells expressing activation and exhaustion markers, but not with viral load or CD4+ T-cell count. Plasma sST2 levels also correlated with plasma levels of gut mucosal damage, microbial translocation and kynurenine/tryptophan ratio and for some markers of inflammation. Prospective analyses showed that early antiretroviral therapy had no impact on sST2 levels, whereas longer treatment duration initiated during CHI normalized sST2. Conclusion: As sST2 levels were elevated in EHI and were correlated with CD8+ T-cell count, immune activation, and microbial translocation, sST2 may serve as a marker of disease progression, gut damage and may directly contribute to HIV pathogenesis. PMID:27045377

  20. Modulation of pulmonary fibrosis by IL-13Rα2.

    Science.gov (United States)

    Lumsden, Robert V; Worrell, Julie C; Boylan, Denise; Walsh, Sinead M; Cramton, Jennifer; Counihan, Ian; O'Beirne, Sarah; Medina, Maria Fe; Gauldie, Jack; Fabre, Aurelie; Donnelly, Seamas C; Kane, Rosemary; Keane, Michael P

    2015-04-01

    Pulmonary fibrosis is a progressive and fatal disease that involves the remodeling of the distal airspace and the lung parenchyma, which results in compromised gas exchange. The median survival time once diagnosed is less than three years. Interleukin (IL)-13 has been shown to play a role in a number of inflammatory and fibrotic diseases. IL-13 modulates its effector functions via a complex receptor system that includes the IL-4 receptor (R) α, IL-13Rα1, and the IL-13Rα2. IL-13Rα1 binds IL-13 with low affinity, yet, when it forms a complex with IL-4α, it binds with much higher affinity, inducing the effector functions of IL-13. IL-13Rα2 binds IL-13 with high affinity but has a short cytoplasmic tail and has been shown to act as a nonsignaling decoy receptor. Transfection of fibroblasts and epithelial cells with IL-13Rα2 inhibited the IL-13 induction of soluble collagen, TGF-β, and CCL17. Adenoviral overexpression of IL-13Rα2 in the lung reduced bleomycin-induced fibrosis. Our work shows that overexpression of IL-13Rα2 inhibits the IL-13 induction of fibrotic markers in vitro and inhibits bleomycin-induced pulmonary fibrosis. In summary our study highlights the antifibrotic nature of IL-13Ra2. Copyright © 2015 the American Physiological Society.

  1. Study on the changes of serum IL-2, IL-6 and TNF-α levels in patients with psoriasis

    International Nuclear Information System (INIS)

    Xie Chuntao

    2007-01-01

    Objective: To investigate the changes of serum IL-2, IL-6 and TNF-α levels in patients with psoriasis. Methods: Serum IL-2, IL-6 and TNF-α levels were measured with KIA in 38 patients with psoriasis and 35 controls. Results: Serum levels of IL-6 and TNF-α were significantly higher in patients with psoriasis than those in controls (P<0.01), but serum IL-2 levels were significantly lower (P<0.01). Conclusion: These cytokines participated in the pathogenesis of psoriasis. Monitoring the changes of their serum levels was helpful for the management of the diseases. (authors)

  2. The clinical significance of T-cells, sIL-2R and TNF in evaluating patients with splenic autotransplantation

    International Nuclear Information System (INIS)

    Wang Haowei; Wu Haorong; Li Juncheng; Wu Jingchang

    2002-01-01

    To study the immunological effects of splenic autotransplantation, forty patients with splenic trauma were divided into two groups equally. One group underwent splenic autotransplantation and another underwent splenectomy. Control group included ten cases. Splenic autotransplantation and splenectomy group were compared with the control group. In the group of splenic autotransplantation, CD3 + , CD4 + , CD8 + , CD4 + /CD8 + dropped and sIL-2R, TNF rose after a week of operation. Then CD3 + , CD4 + , CD8 + , CD4 + /CD8 + rose and sIL-2R, TNF dropped three months later. In the group of splenectomy, CD 3+ , CD4 + , CD8 + and CD4 + /CD8 + dropped persistently, while sIL-2R and TNF rose postoperatively. Result showed splenic autotransplantation can help body to maintain T-cells level and improve the anti-infective ability

  3. Curcumin blocks interleukin (IL)-2 signaling in T-lymphocytes by inhibiting IL-2 synthesis, CD25 expression, and IL-2 receptor signaling

    Energy Technology Data Exchange (ETDEWEB)

    Forward, Nicholas A.; Conrad, David M. [Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia (Canada); Power Coombs, Melanie R.; Doucette, Carolyn D. [Department of Pathology, Dalhousie University, Halifax, Nova Scotia (Canada); Furlong, Suzanne J. [Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia (Canada); Lin, Tong-Jun [Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia (Canada); Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia (Canada); Hoskin, David W., E-mail: d.w.hoskin@dal.ca [Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia (Canada); Department of Pathology, Dalhousie University, Halifax, Nova Scotia (Canada); Department of Surgery, Dalhousie University, Halifax, Nova Scotia (Canada)

    2011-04-22

    Highlights: {yields} Curcumin inhibits CD4{sup +} T-lymphocyte proliferation. {yields} Curcumin inhibits interleukin-2 (IL-2) synthesis and CD25 expression by CD4{sup +} T-lymphocytes. {yields} Curcumin interferes with IL-2 receptor signaling by inhibiting JAK3 and STAT5 phosphorylation. {yields} IL-2-dependent regulatory T-lymphocyte function and Foxp3 expression is downregulated by curcumin. -- Abstract: Curcumin (diferulomethane) is the principal curcuminoid in the spice tumeric and a potent inhibitor of activation-induced T-lymphocyte proliferation; however, the molecular basis of this immunosuppressive effect has not been well studied. Here we show that micromolar concentrations of curcumin inhibited DNA synthesis by mouse CD4{sup +} T-lymphocytes, as well as interleukin-2 (IL-2) and CD25 ({alpha} chain of the high affinity IL-2 receptor) expression in response to antibody-mediated cross-linking of CD3 and CD28. Curcumin acted downstream of protein kinase C activation and intracellular Ca{sup 2+} release to inhibit I{kappa}B phosphorylation, which is required for nuclear translocation of the transcription factor NF{kappa}B. In addition, IL-2-dependent DNA synthesis by mouse CTLL-2 cells, but not constitutive CD25 expression, was impaired in the presence of curcumin, which demonstrated an inhibitory effect on IL-2 receptor (IL-2R) signaling. IL-2-induced phosphorylation of STAT5A and JAK3, but not JAK1, was diminished in the presence of curcumin, indicating inhibition of critical proximal events in IL-2R signaling. In line with the inhibitory action of curcumin on IL-2R signaling, pretreatment of CD4{sup +}CD25{sup +} regulatory T-cells with curcumin downregulated suppressor function, as well as forkhead box p3 (Foxp3) expression. We conclude that curcumin inhibits IL-2 signaling by reducing available IL-2 and high affinity IL-2R, as well as interfering with IL-2R signaling.

  4. IL-2/anti-IL-2 mAb immunocomplexes: A renascence of IL-2 in cancer immunotherapy?

    Czech Academy of Sciences Publication Activity Database

    Tomala, Jakub; Kovář, Marek

    2016-01-01

    Roč. 5, č. 3 (2016), e1102829 ISSN 2162-402X R&D Projects: GA ČR GA13-12885S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:61388971 Keywords : Anti-IL-2 mAb * cancer immunotherapy * IL-2 Subject RIV: EE - Microbiology, Virology Impact factor: 7.719, year: 2016

  5. Study on the changes of serum soluble IL-2 receptor (SIL-2R) levels and distribution pattern of peripheral blood T-cell subsets after treatment in pediatric patients with Bronchopneumonia

    International Nuclear Information System (INIS)

    Chen Chuanbin

    2005-01-01

    Objective:To investigate the significance of changes of serum SIL-2R levels and T-cell subsets distribution type after treatment in pediatric patients with bronchopneumonia. Methods: Serum SIL-2R levels (with ELISA) and peripheral blood T-cell subset distribution pattern (with monoclonal antibody technique) were determined in 33 pediatric patients with broncho-pneumonia and 30 controls. Results: Before treatment, the serum SIL-2R levels in the patients were significantly higher than those in normal controls (P 0.05). Serum SIL-2R levels were positively correlated with CD4/CD8 ratio. Conclusion: Detection of serum SIL-2R levels and CD4/CD8 ratio is clinically useful in the management of pediatric patients with bronchopneumonia. (authors)

  6. [Correlation of serum IL-16, IL-18 levels and immunoglobulins in children with asthma].

    Science.gov (United States)

    Xue, Yi-Nan; Zou, Xian-De; Wu, Jia-Ling

    2006-02-01

    This study examined the changes of serum levels of interleukin (IL)-16, IL-18 and immunoglobulins and the correlation of serum IL-16, IL-18 levels and immunoglobulins in children with asthma and aimed to explore the role of IL-16, IL-18 and immunoglobulins in the pathogenesis of asthma. Thirty-four children with asthma and 21 age and gender-matched healthy children were enrolled in this study. The levels of IL-16, IL-18 and immunoglobulin E (IgE) were determined using ELISA. Immunoglobulin G (IgG), immunoglobulin M (IgM) and immunoglobulin A (IgA) were detected by immunoturbidimetry. The levels of IL-16, IL-18 and IgE in patients with asthma at both acute attack and convalescence stages were significantly higher than those in healthy controls. An increased IgG and a decreased IgA levels were found in asthmatic patients at the acute attack stage. There was a positive correlation between the IL-16 and IL-18 levels at both acute attack and convalescence stages of asthma (r=0.70, P attack stage of asthma (r=0.624, P asthma. The immunologic imbalance exists in children with asthma at both acute attack and convalescence stages. Anti-allergic therapy should be administered through the acute attack to the convalescence stages of asthma.

  7. Distinct spatial relationship of interleukin-9 receptor with IL-2R and MHC glycoproteins in human T lymphoma cells

    OpenAIRE

    Nizsalóczki, Enikő; Csomós, István; Nagy, Péter; Fazekas, Zsolt; Goldman, Carolyn K.; Waldmann, Thomas A.; Damjanovich, Sándor; Vámosi, György; Mátyus, László; Bodnár, Andrea

    2014-01-01

    The IL-9R consists of the α-subunit and the γc-chain shared with other cytokine receptors, including IL-2R, an important regulator of T cells. We have previously shown that IL-2R is expressed in common clusters with MHC glycoproteins in lipid rafts of human T lymphoma cells raising the question what the relationship between clusters of IL-2R/MHC and IL-9R is. Confocal microscopic co-localization and FRET experiments capable of detecting membrane protein organization at different size scales r...

  8. Type I IL-1 Receptor (IL-1RI as Potential New Therapeutic Target for Bronchial Asthma

    Directory of Open Access Journals (Sweden)

    Jyh-Hong Lee

    2010-01-01

    Full Text Available The IL-1R/TLR family has been receiving considerable attention as potential regulators of inflammation through their ability to act as either activators or suppressors of inflammation. Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness, allergic inflammation, elevated serum total, allergen-specific IgE levels, and increased Th2 cytokine production. The discovery that the IL-1RI–IL-1 and ST2IL-33 pathways are crucial for allergic inflammation has raised interest in these receptors as potential targets for developing new therapeutic strategies for bronchial asthma. This paper discusses the current use of neutralizing mAb or soluble receptor constructs to deplete cytokines, the use of neutralizing mAb or recombinant receptor antagonists to block cytokine receptors, and gene therapy from experimental studies in asthma. Targeting IL-1RI–IL-1 as well as ST2IL-33 pathways may promise a disease-modifying approach in the future.

  9. rs1004819 is the main disease-associated IL23R variant in German Crohn's disease patients: combined analysis of IL23R, CARD15, and OCTN1/2 variants.

    Directory of Open Access Journals (Sweden)

    Jürgen Glas

    Full Text Available BACKGROUND: The IL23R gene has been identified as a susceptibility gene for inflammatory bowel disease (IBD in the North American population. The aim of our study was to test this association in a large German IBD cohort and to elucidate potential interactions with other IBD genes as well as phenotypic consequences of IL23R variants. METHODS: Genomic DNA from 2670 Caucasian individuals including 833 patients with Crohn's disease (CD, 456 patients with ulcerative colitis (UC, and 1381 healthy unrelated controls was analyzed for 10 IL23R SNPs. Genotyping included the NOD2 variants p.Arg702Trp, p.Gly908Arg, and p.Leu1007fsX1008 and polymorphisms in SLC22A4/OCTN1 (1672 C-->T and SLC22A5/OCTN2 (-207 G-->C. RESULTS: All IL23R gene variants analyzed displayed highly significant associations with CD. The strongest association was found for the SNP rs1004819 [P = 1.92x10(-11; OR 1.56; 95 % CI (1.37-1.78]. 93.2% of the rs1004819 TT homozygous carriers as compared to 78% of CC wildtype carriers had ileal involvement [P = 0.004; OR 4.24; CI (1.46-12.34]. The coding SNP rs11209026 (p.Arg381Gln was protective for CD [P = 8.04x10(-8; OR 0.43; CI (0.31-0.59]. Similar, but weaker associations were found in UC. There was no evidence for epistasis between the IL23R gene and the CD susceptibility genes CARD15 and SLC22A4/5. CONCLUSION: IL23R is an IBD susceptibility gene, but has no epistatic interaction with CARD15 and SLC22A4/5. rs1004819 is the major IL23R variant associated with CD in the German population, while the p.Arg381Gln IL23R variant is a protective marker for CD and UC.

  10. Differential expression of IL-6/IL-6R and MAO-A regulates invasion/angiogenesis in breast cancer.

    Science.gov (United States)

    Bharti, Rashmi; Dey, Goutam; Das, Anjan Kumar; Mandal, Mahitosh

    2018-04-26

    Monoamine oxidases (MAO) are mitochondrial enzymes functioning in oxidative metabolism of monoamines. The action of MAO-A has been typically described in neuro-pharmacological domains. Here, we have established a co-relation between IL-6/IL-6R and MAO-A and their regulation in hypoxia induced invasion/angiogenesis. We employed various in-vitro and in-vivo techniques and clinical samples. We studied a co-relation among MAO-A and IL-6/IL-6R and tumour angiogenesis/invasion in hypoxic environment in breast cancer model. Activation of IL-6/IL-6R and its downstream was found in hypoxic cancer cells. This elevation of IL-6/IL-6R caused sustained inhibition of MAO-A in hypoxic environment. Inhibition of IL-6R signalling or IL-6R siRNA increased MAO-A activity and inhibited tumour angiogenesis and invasion significantly in different models. Further, elevation of MAO-A with 5-azacytidine (5-Aza) modulated IL-6 mediated angiogenesis and invasive signatures including VEGF, MMPs and EMT in hypoxic breast cancer. High grade invasive ductal carcinoma (IDC) clinical specimen displayed elevated level of IL-6R and depleted MAO-A expression. Expression of VEGF and HIF-1α was unregulated and loss of E-Cadherin was observed in high grade IDC tissue specimen. Suppression of MAO-A by IL-6/IL-6R activation promotes tumour angiogenesis and invasion in hypoxic breast cancer environment.

  11. Study on the changes of serum IL-2, IL-6 and TNF-α levels in patients with chronic glomerulonephritis

    International Nuclear Information System (INIS)

    Xie Jianping; Feng Jiangchao; Zhang Guoyuan; Xiong Gang; Tu Lirong; Xia Chengyun

    2003-01-01

    Objective: To investigate the changes of serum IL-2, IL-6 and TNF-α levels in patients with chronic glomerulonephritis of various types and stages. Methods: Serum IL-2, IL-6 and TNF-α levels were measured with RIA in 71 patients with chronic glomerulonephritis and 36 controls. Results: 1) Serum levels of IL-6 and TNF-α were significantly higher in patients with chronic glomerulonephritis than those in controls (p<0.01) but serum IL-2 levels were significantly lower in the patients (p<0.01). 2)Serum IL-6 and TNF-α levels were positively correlated to BUN levels (p<0.01). 3)There were no significant differences of these cytokines levels among the different types of patients (i.e. general type n=18, nephrotic type n=33 and hypertensive type n=20). Conclusion: These cytokines participated in the pathogenesis of chronic glomerulonephritis. Monitoring the changes of their serum levels was helpful for the management of the disease

  12. Clinical significance of changes of serum IL-2, IL-6 and TNF-α levels after treatment in patients with periodontitis

    International Nuclear Information System (INIS)

    Wei Dong

    2005-01-01

    Objective: To investigate the changes of serum IL-2, IL-6 and TNF-α levels after one month of comprehensive treatment in patients with periodontitis. Methods: Serum IL-2, IL-6 and TNF-α levels were measured with RIA in 48 patients with periodontitis both before and after treatment as well as in 35 controls. Results: Before treatment, serum levels of IL-6, TNF- α in the patients were significantly higher and IL-2 levels were significantly lower than those in the controls (both P 0.05). However, the IL-2 levels were still significantly lower than those in controls (P<0.05). Conclusion: There was disturbance of immuno-modulation in patients with periodontitis as expressed by the changes of cytokines levels in the course of the disease. (authors)

  13. Cytokines and soluble adhesion molecules in children and adolescents with a tic disorder

    NARCIS (Netherlands)

    Bos-Veneman, Netty G.P.; Bijzet, Johan; Limburg, Pieter C.; Minderaa, Rudolf; Kallenberg, C.; Hoekstra, Pieter J.

    2010-01-01

    Aim: Dysregulation of the immune system may play a role in tic disorders. We screened for immune disturbances by investigating serum levels of cytokines and soluble adhesion molecules in patients with a tic disorder. Methods: Serum levels of interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12, soluble IL-2

  14. Effect of long-term inhalation of glucocorticoids on the level of leptin, IL-13 and IL-2 in bronchial asthmatic children

    International Nuclear Information System (INIS)

    Pan Jiongwei

    2011-01-01

    Objective: To determine the effect of long-term inhalation of glucocorticoids on the level of leptin, IL-13, and IL-2 in bronchial asthmatic patient. Methods: Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum IL-13 and IL-2 level in 60 healthy persons (normal control group) and 70 bronchial asthma patients untreated and 3, 6, 12 months post-treatment, meanwhile leptin was determined by radio immunoassay. Results: The serum levels of leptin, Il-13, and IL-2 in were significantly increased in patient with bronchial asthma compared with that in the normal control group. The serum levels of leptin, IL-13, and IL-2 in children with asthma were decreased gradually after inhaling glucocorticoids for 3 months (P<0.05). The treatment of inhaled glucocorticoids for 6 and 12 months can attenuate the elevation of leptin, IL-13, and IL-2 compared with that before the treatment. Conclusion: Long-term inhaled glucocorticoid is an important means for asthma, and the effects are related to the decrease of level of leptin, IL-13, and IL-2. (authors)

  15. DIFFERENTIAL BINDING OF HUMAN INTERLEUKIN-1 (IL-1) RECEPTOR ANTAGONIST TO NATURAL AND RECOMBINANT SOLUBLE AND CELLULAR IL-1 TYPE-I RECEPTORS

    DEFF Research Database (Denmark)

    Svenson, Morten; Nedergaard, Susanne; Heegaard, Peter M. H.

    1995-01-01

    antagonist (IL-1ra). Recombinant soluble human IL-1RI expressed in COS cells (sIL-1RI) consists of the extracellular part of the receptor and binds all three known IL-1 species but preferentially to IL-1ra. We further characterized the sizes and binding of IL-1raBF and sIL-1RI to IL-1ra by polyacrylamide gel...... electrophoresis in the presence of sodium dodecylsulfate, ligand binding interference analyses, N-glycosidase treatment, concanavalin A affinity chromatography, and with the use of monoclonal antibodies (mAb) to human recombinant IL-1ra. We also evaluated the binding of IL-1ra to cellular IL-1RI on MRC5...... binding of both molecules to IL-1ra. Both factors blocked binding of IL-1ra to cellular IL-1RI, as did mAb to IL-1ra, but the sites on IL-1ra which bound to the mAb, and to IL-1raBF and sIL-1RI, differed. We conclude that there are important differences between the natural and recombinant forms of soluble...

  16. Changes of serum IL-2, IL-4, IL-10 and IFN-γ levels after treatment with 131I-17-allylamino-17-demethoxygeldanamycin in VX2 rabbit models

    International Nuclear Information System (INIS)

    Gao Wen; Liu Lu; Zhou Yun

    2007-01-01

    Objective: To study the influence of 131 I-17-allylamino-17-demethoxygeldanamycin( 131 I-17-AAG) therapy on immune function in VX2 rabbit models with transplanted liver cancer. Methods: Serum IL-2, IL-4, IL-10 and IFN-γ levels were measured with RIA in 8 VX2 rabbit models with transplanted liver cancer 1-2 weeks after 10mCi 131 I-17-AAG treatment as well as in 8 controls rabbits (models with tumor but without treatment). Results: 1 week after 10mCi 131 I treatment, the serum IL - 2 and IFN-γ levels were significantly lower in the treated rabbits than those in controls (P 0.05). Serum IL-4 and IL-10 levels in the treated rabbits (both at 1 and 2 week) were not significantly different from those in controls (P>0.05). Conclusion: 131 I-17-AAG treatment had transient effects on cellular immunity with no influence on humoral immunity. As a whole, it is a safe to treat VX2 rabbit models with this preparation. (authors)

  17. Clinical significance of determination of changes of EPS IL-1β, IL-2, IL-10 and LDH5/LDH1 levels in patients with chronic prostatitis

    International Nuclear Information System (INIS)

    Chen Yongchang

    2009-01-01

    Objective: To investigate the clinical significance of the changes of expressed prostatic secretion IL-1β, IL-2, IL-10 and LDH5/LDH1 levels in patients with chronic prostatitis. Methods: Expressed prostatic secretion IL-1β, IL-2, IL-10 (with Radioimmunoassay) and LDH5/LDH1 (with cellulose acetate membrane electrophoresis) levels were determined in 32 patients with chronic prostatitis and 35 controls. These 32 patients were of 3 groups: 1)chronic bacterial prostatitis (CBP, n=10) 2) chronic pelvic pain syndrome IIIA (CPPS IIIA n=9) 3) CPPSIIIB n=13. Results: Expressed prostatic secretion levels of IL-1β, IL-2 and LDH5/LDH1 were significantly higher in patients with chronic bacterial prostatitis (CBP) groups than those in controls (all P 0.05). But the expressed prostatic secretion levels of IL-10 were still significantly lower in patients with chronic nonbacterial prostatitis, chronic pelvic pain syndrome(CPPSIIIB) groups than those in controls (all P<0.05). Conclusion: There were changes of expressed prostatic secretion IL-1β, IL-2, IL-10 and LDH5/LDH1 levels in patients with chronic prostatitis. Combined determination of the expressed prostatic secretion 4 markers levels is valuable for the diagnosis of chronic prostatitis and CPPSIII and for differentiation of CPPSIII types. (authors)

  18. Effect of trans-chalcone on hepatic IL-8 through the regulation of miR-451 in male rats

    Directory of Open Access Journals (Sweden)

    Karimi-Sales Elham

    2018-01-01

    Full Text Available Objective. Trans-chalcone is a chalcone with hepatoprotective and anti-inflammatory effects. However, the mechanism of these positive effects, especially on miR-451 as an inflammatory regulator, is poorly understood. In this regard, this microRNA (miRNA acts by inhibition of hepatic interleukin-8 (IL-8 production in the liver which is one of the main proinflammatory cytokines. Th is study for the first time examined the effect of trans-chalcone on miR-451/IL-8 pathway. Methods. In present study, 21 male rats were randomly divided into 3 groups (n=7 per each group: control which received solvent (NS, groups 2 (N2T and 3 (N6T, which received transchalcone for 2 and 6 weeks, respectively. Hepatic level of miR-451 was measured by qRT-PCR. Serum levels of alanine aminotransferase (ALT and aspartate aminotransferase (AST as well as hepatic level of IL-8 protein were measured. Results. Trans-chalcone decreased hepatic level of IL-8 protein and serum level of ALT aft er 2 weeks of treatment without significant change in hepatic miR-451. Moreover, it increased hepatic level of miR-451 and reduced hepatic IL-8 as well as AST and ALT aft er 6 weeks. Conclusion. Based on the results of present study, miR-451/IL-8 pathway is a possible mechanism for hepatoprotective action of trans-chalcone in long-term.

  19. Three-Dimensional Conformal Radiotherapy in Prostate Cancer Patients: Rise in Interleukin 6 (IL-6) but not IL-2, IL-4, IL-5, Tumor Necrosis Factor-{alpha}, MIP-1-{alpha}, and LIF Levels

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira Lopes, Carlos [Universidade do Vale do Paraiba, Centro de Oncologia Radioterapica do Vale do Paraiba, Universidade do Vale do Paraiba Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraiba, Sao Jose dos Campos, Sao Paulo (Brazil); Callera, Fernando, E-mail: fcallera@gmail.com [Centro de Hematologia Onco-hematologia e Transplantes de Medula Ossea do Vale do Paraiba, Sao Paulo (Brazil)

    2012-03-15

    Purpose: To investigate the effect of radiotherapy (RT) on serum levels of interleukin-2 (IL-2), IL-4, IL-5, IL-6, tumor necrosis factor alpha (TNF-{alpha}), macrophage inflammatory protein-1-alpha (MIP-1-{alpha}) and leukemia inhibitory factor (LIF) in patients with prostate cancer. Methods and Materials: Forty eight patients with prostate cancer received three-dimensional conformal blocking radiation therapy with a linear accelerator. IL-2, IL-4, IL-5, IL-6, TNF-{alpha}, MIP-1-{alpha}, and LIF levels were measured by the related immunoassay kit 1 day before the beginning of RT and during RT at days 15 and 30. Results: The mean IL-2 values were elevated before and during the RT in contrast with those of IL-4, IL-5, IL-6, TNF-{alpha}, MIP-1-{alpha}, and LIF, which were within the normal range under the same conditions. Regarding markers IL-2, IL-4, IL-5, TNF-{alpha}, MIP-1-{alpha}, and LIF, comparisons among the three groups (before treatment and 15 and 30 days during RT) did not show significant differences. Although values were within the normal range, there was a significant rise in IL-6 levels at day 15 of RT (p = 0.0049) and a decline at day 30 to levels that were similar to those observed before RT. Conclusions: IL-6 appeared to peak after 15 days of RT before returning to pre-RT levels. In contrast, IL-2, IL-4, IL-5, TNF-{alpha}, MIP-1-{alpha}, and LIF levels were not sensitive to irradiation. The increased levels of IL-6 following RT without the concurrent elevation of other cytokines involved in the acute phase reaction did not suggest a classical inflammatory response to radiation exposure. Further studies should be designed to elucidate the role of IL-6 levels in patients with prostate cancer treated with RT.

  20. Serum placental growth factor, vascular endothelial growth factor, soluble vascular endothelial growth factor receptor-1 and -2 levels in periodontal disease, and adverse pregnancy outcomes.

    Science.gov (United States)

    Sert, Tuba; Kırzıoğlu, F Yeşim; Fentoğlu, Ozlem; Aylak, Firdevs; Mungan, Tamer

    2011-12-01

    The aim of this study is the evaluation of levels of serum interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), placental growth factor (PIGF), and soluble VEGF receptor (sVEGFR)-1 and -2 in the association between periodontal disease and adverse pregnancy outcomes. One hundred and nine mothers, who recently gave birth, and 51 women who were not recently pregnant, aged 18 to 35 years, were included in this study. The mothers were classified as term birth, preterm birth (PTB), and preterm low birth weight (PLBW) in respect to their gestational age and baby's birth weight. The birth mothers were grouped as having gingivitis or periodontitis. The non-pregnant group also included periodontally healthy patients. Venous blood samples were collected to evaluate serum IL-1β, IL-6, IL-10, TNF-α, VEGF, PIGF, and sVEGFR-1 and -2 levels. Mother's weight, education, and income level were significantly associated with pregnancy outcomes. Serum levels of IL-1β, TNF-α, IL-6, VEGF, and sVEGFR-1 and -2 showed an increase in significance when related to pregnancy. Whereas in the PLBW group IL-1β, VEGF, and sVEGFR-2 levels were increased, in the PTB group sVEGFR-1 levels were increased. Additionally, the patients in the PLBW group with periodontitis had higher serum levels of IL-1β, VEGF, sVEGFR-2, and IL-1β/IL-10. The serum levels of IL-1β, VEGF, and sVEGFR-1 and -2 may have a potential effect on the mechanism of the association between periodontal disease and adverse pregnancy outcomes.

  1. IL-8 induces miR-424-5p expression and modulates SOCS2/STAT5 signaling pathway in oral squamous cell carcinoma.

    Science.gov (United States)

    Peng, Hsuan-Yu; Jiang, Shih-Sheng; Hsiao, Jenn-Ren; Hsiao, Michael; Hsu, Yuan-Ming; Wu, Guan-Hsun; Chang, Wei-Min; Chang, Jang-Yang; Jin, Shiow-Lian Catherine; Shiah, Shine-Gwo

    2016-06-01

    Suppressor of cytokine signaling (SOCS) proteins are negative feedback regulators of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Dysregulation of SOCS protein expression in cancers can be one of the mechanisms that maintain STAT activation, but this mechanism is still poorly understood in oral squamous cell carcinoma (OSCC). Here, we report that SOCS2 protein is significantly downregulated in OSCC patients and its levels are inversely correlated with miR-424-5p expression. We identified the SOCS2 protein, which modulates STAT5 activity, as a direct target of miR-424-5p. The miR-424-5p-induced STAT5 phosphorylation, matrix metalloproteinases (MMPs) expression, and cell migration and invasion were blocked by SOCS2 restoration, suggesting that miR-424-5p exhibits its oncogenic activity through negatively regulating SOCS2 levels. Furthermore, miR-424-5p expression could be induced by the cytokine IL-8 primarily through enhancing STAT5 transcriptional activity rather than NF-κB signaling. Antagomir-mediated inactivation of miR-424-5p prevented the IL-8-induced cell migration and invasion, indicating that miR-424-5p is required for IL-8-induced cellular invasiveness. Taken together, these data indicate that STAT5-dependent expression of miR-424-5p plays an important role in mediating IL-8/STAT5/SOCS2 feedback loop, and scavenging miR-424-5p function using antagomir may have therapeutic potential for the treatment of OSCC. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Plasma IL-17A levels in patients with late-life depression.

    Science.gov (United States)

    Saraykar, Smita; Cao, Bo; Barroso, Lucelia S; Pereira, Kelly S; Bertola, Laiss; Nicolau, Mariana; Ferreira, Jessica D; Dias, Natalia S; Vieira, Erica L; Teixeira, Antonio L; Silva, Ana Paula M; Diniz, Breno S

    2018-01-01

    A consistent body of research has confirmed that patients with major depressive disorder (MDD) have increased concentrations of pro-inflammatory cytokines, including IL-6, TNF-α, IL-1β, the soluble IL-2 receptor, and C-reactive protein, compared to controls; however, there is limited information on IL-17A in MDD. Moreover, information about IL-17A in older populations, i.e., patients with late-life depression (LLD), is conspicuously missing from the literature. The purpose of this study was to investigate the role of IL-17A in LLD. A convenience sample of 129 individuals, 74 with LLD and 55 non-depressed controls, were enrolled in this study. The Mann-Whitney U test was used to compare plasma IL-17A levels between LLD and controls subjects, and Spearman's rank order correlation was used to investigate correlation of these levels with clinical, neuropsychological, and cognitive assessments. Plasma IL-17A levels were not statistically different between LLD patients and controls (p = 0.94). Among all subjects (LLD + control), plasma IL-17A did not correlate significantly with depressive symptoms (rho = -0.009, p = 0.92) but a significant correlation was observed with cognitive assessments (rho = 0.22, p = 0.01). Our findings do not support an association between plasma IL-17A levels and LLD. Nevertheless, IL-17A may be associated with cognitive impairment in LLD patients. If this finding is confirmed in future longitudinal studies, modulation of the T-helper 17 cell (Th17) immune response may be a treatment target for cognitive impairment in this population.

  3. Effects of flurbiprofen axetil on postoperative serum IL-2 and IL-6 levels in patients with colorectal cancer.

    Science.gov (United States)

    Jiang, W W; Wang, Q H; Peng, P; Liao, Y J; Duan, H X; Xu, M; Li, Y; Zhang, P B

    2015-12-09

    We explored the effects of flurbiprofen axetil on interleukin (IL)-2 and IL-6 levels in postoperative patients with colorectal cancer. A total of 120 patients (American Society of Anesthesiologists I and II) scheduled to undergo colorectal cancer surgery were randomly divided into 3 groups (N = 40 in each group): flurbiprofen axetil group (group F), morphine group (group M), and tramadol group (group T). Group M received 0.1 mg/kg morphine, group T received 1.5 mg/kg tramadol, and group F received 1.5 mg/kg flurbiprofen axetil. Patients in the 3 groups were administered treatments through intravenous injection 10 min before surgery. Serum IL-2 and IL-6 levels were detected. Postoperative adverse reactions were recorded, such as nausea, vomiting, and pruritus. The serum IL-6 level of the 3 groups increased 3 h after surgery. Compared with group M, IL-6 level was higher in group T and group F at 1 day after the surgery, and the differences between group M and the other groups were significant (P Flurbiprofen axetil promoted the secretion of IL-2 and inhibited IL-6; additionally, flurbiprofen axetil may have a lower incidence of adverse reactions compared to other treatments.

  4. Increasing the biological activity of IL-2 and IL-15 through complexing with anti-IL-2 mAbs and Il-15Ralfa-Fc chimera

    Czech Academy of Sciences Publication Activity Database

    Votavová, Petra; Tomala, Jakub; Kovář, Marek

    2014-01-01

    Roč. 195, č. 1 (2014), s. 1-10 ISSN 0165-2478 R&D Projects: GA ČR GAP301/11/0325; GA MŠk(CZ) ED1.1.00/02.0109; GA ČR GA13-12885S Institutional support: RVO:61388971 Keywords : IL-2 * IL-15 * chimera Subject RIV: EC - Immunology Impact factor: 2.512, year: 2014

  5. Interleukin-2 (rIL-2)-induced lymphokine-activated killer (LAK) cells and their precursors express the VGO1 antigen

    International Nuclear Information System (INIS)

    Denegri, J.F.; Peterson, J.; Tilley, P.

    1989-01-01

    Precursor and effector cells of recombinant interleukin-2 (r-IL-2)-induced lymphokine-activated killer (LAK) activity were investigated for their expression of VGO1. Peripheral blood lymphocytes (PBL) from normal donors were purified and separated in a FACS 420 into VGO1+- and VGO1- cell fractions before and after culture for 96 hr with 100 U/ml of r-IL-2. Their lytic activity against K 562 and Daudi cells was measured in a 51Cr release assay. The majority, if not all, of the LAK effector and precursor cells was VGO1+ lymphocytes. The expression of VGO1 by LAK precursor cells remained stable under the culture conditions used in our experiments. VGO1- lymphocytes cultured with r-IL-2 demonstrated neither LAK-induced activity nor expression of VGO1 antigen

  6. Aspirin reduces serum anti-melanocyte antibodies and soluble interleukin-2 receptors in vitiligo patients

    International Nuclear Information System (INIS)

    Zailaie, Mohamad Z.

    2005-01-01

    Increased serum levels of certain immunologic markers including immunoglobulin G (IgG) anti-melanocyte/ vitiligo antibodies (V-IgG) and soluble interleukin-2 receptors (sIL-2R) are associated with augmented humoral and cellular immunity involved in melanocyte cytotoxicity during the active phase of non-segmental vitiligo. Recent reports have shown that, aspirin possesses a wide range of immunomodulatory and antioxidant properties. Therefore, the aim of the present study is to investigate the effect of long-term treatment of vitiligo patients with low-dose oral aspirin on serum V-IgG activity and sIL-2R concentration. The present study was carried out at the Vitiligo Unit, King Abdul-Aziz University Medical Center, Jeddah, Kingdom of Saudi Arabia between March and October 2003. Eighteen female and 14 male patients with a recent onset of non-segmental vitiligo were divided into 2 equal groups. One group received a daily single dose of oral aspirin (300 mg) and the second group received only placebo for a period of 12 weeks. Serum V-IgG activity and sIL-2R concentration were determined before and at the end of treatment period. The V-IgG activity was measured using cellular enzyme-linked immunosorbent assay (ELISA) following incubation of IgG antibodies with an adult cultured melanocytes. Serum sIL-2R concentration was measured using the highly sensitive quantitative sandwich ELISA utilizing a commercially available kit. As expected, the serum V-IgG activity and sIL-2R concentration of the active vitiligo patients (0.81 +/- 0.23 optical density (O.D.), 1428 +/- 510 pg/ml) were significantly increased compared with that of controls (0.27 +/- 0.1 O.D., 846 +/- 312 pg/ml; p<0.05, p<0.01). Aspirin-treated vitiligo patients showed significant decrease in serum V-IgG activity and sIL-2R concentration (0.32 +/- 0.08 O.D., 756 +/- 216 pg/ml) compared with that of placebo-treated patients (0.83 +/- 0.19 O.D., 1327 +/- 392 pg/ml; p<0.01). Low-dose oral aspirin treatment of

  7. Clinical value of determination of changes of serum Gas, IL-2, IL-10 and IL-18 levels after transfusion of Red blood cells in patients with peptic ulcer

    International Nuclear Information System (INIS)

    Liu Tingting; Li Xinghua

    2011-01-01

    Objective: To investigation the changes of serum Gas, IL-2, IL-10 and IL-18 contents after transfusion of red blood cells in patients with peptic ulcer. Methods: Serum Gas, IL-2, IL-10 (with RIA), serum IL-18 (with ELISA) levels were measured in 31 patients with peptic ulcer and 35 controls. Results: Before transfusion,the serum IL-2 level in the patients was significantly lower than that in controls (P 0.05). Conclusion: Detection of serum Gas, IL-2, IL-10 and IL-18 levels is clinically useful for monitoring progress and favourable prognosis of patients with peptic ulcer possess important clinical value. (authors)

  8. IL-6 Improves Energy and Glucose Homeostasis in Obesity via Enhanced Central IL-6 trans-Signaling.

    Science.gov (United States)

    Timper, Katharina; Denson, Jesse Lee; Steculorum, Sophie Marie; Heilinger, Christian; Engström-Ruud, Linda; Wunderlich, Claudia Maria; Rose-John, Stefan; Wunderlich, F Thomas; Brüning, Jens Claus

    2017-04-11

    Interleukin (IL)-6 engages similar signaling mechanisms to leptin. Here, we find that central application of IL-6 in mice suppresses feeding and improves glucose tolerance. In contrast to leptin, whose action is attenuated in obesity, the ability of IL-6 to suppress feeding is enhanced in obese mice. IL-6 suppresses feeding in the absence of neuronal IL-6-receptor (IL-6R) expression in hypothalamic or all forebrain neurons of mice. Conversely, obese mice exhibit increased soluble IL-6R levels in the cerebrospinal fluid. Blocking IL-6 trans-signaling in the CNS abrogates the ability of IL-6 to suppress feeding. Furthermore, gp130 expression is enhanced in the paraventricular nucleus of the hypothalamus (PVH) of obese mice, and deletion of gp130 in the PVH attenuates the beneficial central IL-6 effects on metabolism. Collectively, these experiments indicate that IL-6 trans-signaling is enhanced in the CNS of obese mice, allowing IL-6 to exert its beneficial metabolic effects even under conditions of leptin resistance. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  9. IL-6 Improves Energy and Glucose Homeostasis in Obesity via Enhanced Central IL-6 trans-Signaling

    Directory of Open Access Journals (Sweden)

    Katharina Timper

    2017-04-01

    Full Text Available Interleukin (IL-6 engages similar signaling mechanisms to leptin. Here, we find that central application of IL-6 in mice suppresses feeding and improves glucose tolerance. In contrast to leptin, whose action is attenuated in obesity, the ability of IL-6 to suppress feeding is enhanced in obese mice. IL-6 suppresses feeding in the absence of neuronal IL-6-receptor (IL-6R expression in hypothalamic or all forebrain neurons of mice. Conversely, obese mice exhibit increased soluble IL-6R levels in the cerebrospinal fluid. Blocking IL-6 trans-signaling in the CNS abrogates the ability of IL-6 to suppress feeding. Furthermore, gp130 expression is enhanced in the paraventricular nucleus of the hypothalamus (PVH of obese mice, and deletion of gp130 in the PVH attenuates the beneficial central IL-6 effects on metabolism. Collectively, these experiments indicate that IL-6 trans-signaling is enhanced in the CNS of obese mice, allowing IL-6 to exert its beneficial metabolic effects even under conditions of leptin resistance.

  10. IL-4 function can be transferred to the IL-2 receptor by tyrosine containing sequences found in the IL-4 receptor alpha chain.

    Science.gov (United States)

    Wang, H Y; Paul, W E; Keegan, A D

    1996-02-01

    IL-4 binds to a cell surface receptor complex that consists of the IL-4 binding protein (IL-4R alpha) and the gamma chain of the IL-2 receptor complex (gamma c). The receptors for IL-4 and IL-2 have several features in common; both use the gamma c as a receptor component, and both activate the Janus kinases JAK-1 and JAK-3. In spite of these similarities, IL-4 evokes specific responses, including the tyrosine phosphorylation of 4PS/IRS-2 and the induction of CD23. To determine whether sequences within the cytoplasmic domain of the IL-4R alpha specify these IL-4-specific responses, we transplanted the insulin IL-4 receptor motif (I4R motif) of the huIL-4R alpha to the cytoplasmic domain of a truncated IL-2R beta. In addition, we transplanted a region that contains peptide sequences shown to block Stat6 binding to DNA. We analyzed the ability of cells expressing these IL-2R-IL-4R chimeric constructs to respond to IL-2. We found that IL-4 function could be transplanted to the IL-2 receptor by these regions and that proliferative and differentiative functions can be induced by different receptor sequences.

  11. Clinical significance of changes of serum IL-2, IL-6 and gastrin levels before and after treatment in patients with chronic eczema

    International Nuclear Information System (INIS)

    Mou Xudong; Ren Hong

    2009-01-01

    Objective: To explore the clinical significance of changes of serum IL-2, IL-6 and gastrin levels after treatment in patients with chronic eczema. Methods: Serum IL-2, IL-6 and gastin were detected with RIA both before and after treatment in 38 patients with chronic eczema and 35 controls. Results: Before treatment, serum IL-2 levels in the patients were significantly lower than those in the controls (P 0.05), however, the IL-2 levels were still significantly lower than those in controls (P>0.05). Conclusion: Serum IL-2, IL-6 and gastrin levels in the patients with chronic eczema were closely related to the severity of the diseases process and could be taken as indicator of treatment efficacy. (authors)

  12. Whole Genome DNA Methylation Analysis of Obstructive Sleep Apnea: IL1R2, NPR2, AR, SP140 Methylation and Clinical Phenotype.

    Science.gov (United States)

    Chen, Yung-Che; Chen, Ting-Wen; Su, Mao-Chang; Chen, Chung-Jen; Chen, Kuang-Den; Liou, Chia-Wei; Tang, Petrus; Wang, Ting-Ya; Chang, Jen-Chieh; Wang, Chin-Chou; Lin, Hsin-Ching; Chin, Chien-Hung; Huang, Kuo-Tung; Lin, Meng-Chih; Hsiao, Chang-Chun

    2016-04-01

    We hypothesized that DNA methylation patterns may contribute to disease severity or the development of hypertension and excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea (OSA). Illumina's (San Diego, CA, USA) DNA methylation 27-K assay was used to identify differentially methylated loci (DML). DNA methylation levels were validated by pyrosequencing. A discovery cohort of 15 patients with OSA and 6 healthy subjects, and a validation cohort of 72 patients with sleep disordered breathing (SDB). Microarray analysis identified 636 DMLs in patients with OSA versus healthy subjects, and 327 DMLs in patients with OSA and hypertension versus those without hypertension. In the validation cohort, no significant difference in DNA methylation levels of six selected genes was found between the primary snoring subjects and OSA patients (primary outcome). However, a secondary outcome analysis showed that interleukin-1 receptor 2 (IL1R2) promoter methylation (-114 cytosine followed by guanine dinucleotide sequence [CpG] site) was decreased and IL1R2 protein levels were increased in the patients with SDB with an oxygen desaturation index > 30. Androgen receptor (AR) promoter methylation (-531 CpG site) and AR protein levels were both increased in the patients with SDB with an oxygen desaturation index > 30. Natriuretic peptide receptor 2 (NPR2) promoter methylation (-608/-618 CpG sites) were decreased, whereas levels of both NPR2 and serum C type natriuretic peptide protein were increased in the SDB patients with EDS. Speckled protein 140 (SP140) promoter methylation (-194 CpG site) was increased, and SP140 protein levels were decreased in the patients with SDB and EDS. IL1R2 hypomethylation and AR hypermethylation may constitute an important determinant of disease severity, whereas NPR2 hypomethylation and SP140 hypermethylation may provide a biomarker for vulnerability to EDS in OSA. A commentary on this article appears in this issue on page 723. © 2016

  13. Effects of Shugan Jieyuling self-made on behavior and levels of serum IL-2, IL-6 and cortisol in depression models

    International Nuclear Information System (INIS)

    Li Qiubo; Yao Di; Zhang Ping; Li Youtian; Xu Dan; Jiang Sailin; Xu Caiyun

    2005-01-01

    Objective: To study the effects of Shugan Jieyuling self-made (SJSM) on behavior, levels of serum IL-2, IL-6 and cortisol in depression model mice. Methods: The adult mice separately raised and treated with chronic unpredictable middle stress stimulus were used to establish depression models. The curative effect of SJSM was observed in depression model mice. The changes of weight and behavior were detected in a period. Radioimmunoassay (RIA) was used to examine the contents of serum IL-2, IL-6 and cortisol levels. Results: The increased weights of the depression model mice were declined compared with the normal mice before administration. The mental state and behavior of the depression mice were changed. The mice were starling, dreadful, helpless and immobile. At the same time the contents of serum IL-2, IL-6 and cortisol were obviously lower than those of the normal mice. SJSM (large and low doses) and Baiyoujie changed the increased weights and behaviors of the depression after administration for 21 d. The mental state was meliorated simultaneously, and the serum IL-2, IL-6 and cortisol levels in the depression model mice were decreased significantly compared with normal mice. Conclusion: The levels of serum IL-2, IL-6 and cortisol may be the guideline for the diagnosis of depression disease. SJSM can obviously improve both the symptoms of the depression models and the levels of serum IL-2, IL-6 and cortisol. (authors)

  14. Changes of serum levels of some relevant cytokine (IL-2, IL-6, TNF-α) after antithyroid treatment in patients with graves' disease

    International Nuclear Information System (INIS)

    Ren Xiaohua; Jiang Boyong

    2010-01-01

    Objective: To study the effect of antithyroid treatment on the changes of serum levels of IL-2, IL-6 and TNF-α in patients with Graves' disease. Methods: Serum levels of IL-2, IL-6 and TNF-α were measured with RIA in 30 patients with Graves' disease (both before and after treatment with antithyroid drug) and 30 controls. Results: Before treatment serum levels of IL-6 and TNF-α in the patients were significantly higher than those in controls (P 0.05). Conclusion: Changes of serum IL-2, IL-6 and TNF-α levels might be important in the pathogenesis of Graves' disease. (authors)

  15. Expression level and clinical significance of IL-2, IL-6 and TGF-β in elderly patients with goiter and hyperthyroidism.

    Science.gov (United States)

    Lv, L-F; Jia, H-Y; Zhang, H-F; Hu, Y-X

    2017-10-01

    To investigate the level of expression and the clinical significance of IL-2 (interleukin-2), IL-6 (interleukin-6) and TGF-β (transforming growth factor-β) in elderly patients with goiter and hyperthyroidism. Gender, age, course of disease, BMI (Body Mass Index), serum FT3 (Free triiodothyronine-3), FT4 (Free triiodothyronine-4), TT3 (Total triiodothyronine-3), TT4 (Total triiodothyronine-4), TSH (Thyroid Stimulating Hormone) and clinical manifestations on admission and other general clinical data and laboratory examination results were collected and statistically analyzed as case group in 128 elderly patients with goiter and hyperthyroidism. Additional 128 over 60-year-old patients with hyperthyroidism were selected as control group. The thyroid tissue of these patients and the control group were examined by fine needle aspiration biopsy. The expressions of IL-2, IL-6, TGF-β of the thyroid tissue in all patients were detected by immunohistochemistry, qRT-PCR (Real-time Quantitative Polymerase Chain Reaction) and Western blot method respectively, and the statistical analysis was carried out. p hyperthyroidism and thyroid enlargement (p hyperthyroidism, and symptoms of exophthalmos, the level of expression of IL-6 was significantly higher than that of patients without exophthalmos (p hyperthyroidism and symptoms of exophthalmos, and the patients with goiter, hyperthyroidism without symptoms of exophthalmos, IL-2 and TGF-β expression level were not different (p > 0.05). The expression levels of IL-2, IL-6, and TGF-β were significantly increased in the patients with senile goiter and hyperthyroidism, but in the senile patients with goiter, hyperthyroidism and exophthalmos symptoms, IL-6 levels were significantly higher than those without exophthalmos. The use of IL-2, IL-6, and TGF-β is of great significance in the diagnosis of goiter with hyperthyroidism, especially for elderly patients with atypical clinical symptoms of hyperthyroidism.

  16. Soluble intercellular adhesion molecule-1 and interleukin-6 levels reflect endothelial dysfunction in patients with primary hypercholesterolaemia treated with atorvastatin.

    Science.gov (United States)

    Nawawi, H; Osman, N S; Annuar, R; Khalid, B A K; Yusoff, K

    2003-08-01

    Adhesion molecules and cytokines are involved in the pathogenesis of intimal injury in atherosclerosis but their relationship with endothelial function remains unclear. The objectives of this study were to examine the effects of atorvastatin on soluble adhesion molecules, interleukin-6 (IL-6) and brachial artery endothelial-dependent flow mediated dilatation (FMD) in patients with familial (FH) and non-familial hypercholesterolaemia (NFH). A total of 74 patients (27 FH and 47 NFH) were recruited. Fasting lipid profiles, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular-cellular adhesion molecule-1 (sVCAM-1), E-selectin, IL-6 and FMD were measured at baseline, 2 weeks, 3 and 9 months post-atorvastatin treatment (FH--80 mg/day, NFH--10 mg/day). In both groups, compared to baseline, sICAM-1 levels were significantly reduced at 2 weeks, further reduced at 3 months and maintained at 9 months (P<0.0001). The IL-6 levels were significantly reduced at 3 months and 9 months compared to baseline for FH (P<0.005) and NFH (P<0.0001). In both groups, the FMD at 2 weeks was higher than baseline (P<0.005), with progressive improvement up to 9 months. FMD was negatively correlated with sICAM-1 and IL-6. In conclusion, both low and high doses of atorvastatin lead to early progressive improvement in endothelial function in patients with primary hypercholesterolaemia. sICAM-1 and IL-6 levels reflect endothelial dysfunction in these patients.

  17. Phase equilibrium of (CO2 + 1-aminopropyl-3-methylimidazolium bromide + water) electrolyte system and effects of aqueous medium on CO2 solubility: Experiment and modeling

    International Nuclear Information System (INIS)

    Chen, Ying; Guo, Kaihua; Bi, Yin; Zhou, Lan

    2017-01-01

    Highlights: • Phase and chemical equilibrium data for (CO 2 + [APMIm]Br + H 2 O) electrolyte system. • A modified eNRTL model for CO 2 solubility in the amino-based IL aqueous solution. • Effects of aqueous medium on both chemical and physical dissolution of CO 2 . • The correlative coefficient, R s ∗ , for the Henry’s constant of the solution. • New parameters for the segments interaction and the chemical equilibrium constants. - Abstract: New experimental data for solubility of carbon dioxide (CO 2 ) in the aqueous solution of 1-aminopropyl-3-methylimidazolium bromide ([APMIm]Br) with four different water mass fractions (0.559, 0.645, 0.765 and 0.858) at T = (278.15–348.15) K with an interval of T = 10 K and p = (0.1237–6.9143) MPa were presented. The electrolyte nonrandom two-liquid (eNRTL) model was modified to be applicable for an ionic liquid (IL) aqueous solution system, by introducing an idle factor β to illustrate the association effect of IL molecules. A solution Henry’s constant for CO 2 solubility in the IL aqueous solution was defined by introducing a correlative coefficient R s ∗ . The vapor-liquid phase equilibrium of the [APMIm]Br-H 2 O-CO 2 ternary system was successfully calculated with the modified eNRTL model. The chemical and physical mechanisms for the ionized CO 2 formation and the molecular CO 2 dissolved in the solution were identified. The effects of aqueous medium on both chemical and physical dissolution of CO 2 in the [APMIm]Br aqueous solution were studied, and a considerable enhancement of the solubility of CO 2 with increase of the water content in the solution was observed.

  18. Association of single nucleotide polymorphisms of IL23R and IL17 with ulcerative colitis risk in a Chinese Han population.

    Directory of Open Access Journals (Sweden)

    Pengli Yu

    Full Text Available BACKGROUND: Previous studies implicated that IL23R and IL17 genes play an important role in autoimmune inflammation. Genome-wide association studies have also identified multiple single nucleotide polymorphisms (SNPs in the IL23R gene region associated with inflammatory bowel diseases. This study examined the association of IL23R and IL17A gene SNPs with ulcerative colitis susceptibility in a population in China. METHODOLOGY: A total of 270 ulcerative colitis and 268 healthy controls were recruited for the analyses of 23 SNPs in the IL23R and IL17A regions. Genomic DNA was extracted and analysis of these 23 SNPs using ligase detection reaction allelic (LDR technology. Genotype and allele associations were calculated using SPSS 13.0 software package. PRINCIPAL FINDINGS: Compared to the healthy controls, the variant alleles IL23R rs7530511, and rs11805303 showed a statistically significant difference for ulcerative colitis susceptibility (0.7% vs 3.3%, P = 0.002; 60.4% vs 53.2%, P = 0.0017, respectively. The linkage disequilibrium (LD patterns of these SNPs were measured and three LD blocks from the SNPs of IL23R and one block from those of IL17A were identified. A novel association with ulcerative colitis susceptibility occurred in haplotypes of IL23R (Block1 H3 P = 0.02; Block2 H2 P = 0.019; Block3 H4 P = 0.029 and IL17A (H4 P = 0.034. Pair-wise analyses showed an interaction between the risk haplotypes in IL23R and IL17A (P = 0.014. CONCLUSIONS: Our study demonstrated that rs7530511, and rs11805303 of IL23R were significantly associated with ulcerative colitis susceptibility in the Chinese population. The most noticeable finding was the linkage of IL23R and IL17A gene region to ulcerative colitis risk due to the gene-gene interaction.

  19. Recombinant Newcastle disease virus (NDV/Anh-IL-2 expressing human IL-2 as a potential candidate for suppresses growth of hepatoma therapy

    Directory of Open Access Journals (Sweden)

    Yunzhou Wu

    2016-09-01

    Full Text Available Newcastle disease virus (NDV have shown oncolytic therapeutic efficacy in preclinical study and are currently approved for clinical trials. NDV Anhinga strain which is a mesogenic strain should be classified as lytic strain and has a therapeutic efficacy in hepatocellular cancer. In this study, we evaluated the capacity of NDV Anhinga strain to elicit immune reaction in vivo and the possibility for using as a vaccine vector for expressing tumor therapeutic factors. Interleukin-2 (IL-2 could boost the immune response against the tumor cells. Therefore, we use NDV Anhinga strain as backbone to construct a recombinant virus (NDV/Anh-IL-2 expressing IL-2. The virus growth curve showed that the production of recombinant NDV/Anh-IL-2 was slightly delayed compared to the wild type. The NDV/Anh-IL-2 strain could express soluble IL-2 and effectively inhibit the growth of hepatocellular carcinoma in vivo. 60 days post-treatment, mice which were completely cured by previous treatment were well protected when rechallenged with the same tumor cell. From the H&E-stained sections, intense infiltration of lymphocyte was observed in the NDV Anhinga strain treated group, especially in NDV/Anh-IL-2 group. The NDV Anhinga strain could not only kill the tumor directly, but could also elicit immune reaction and a potent immunological memory when killing tumor in vivo. In conclusion, the Anhinga strain could be an effective vector for tumor therapy; the recombinant NDV/Anh-IL-2 strain expressing soluble IL-2 is a promising candidate for hepatoma therapy.

  20. Clinical significance of measurement of changes of serum IL-2, IL-4 and IFN-γ levels after treatment in patients with vitiligo

    International Nuclear Information System (INIS)

    Cheng Junmin; Zhou Xiujuan; Zhang Yuhong

    2010-01-01

    Objective: To explore the changes of serum IL-2, IL-4 and IFN-γ levels after treatment in patients with vitiligo. Methods: Serum IL-2 (with RIA) IL-4, IFN-γ (with ELISA) levels were examined in 37 patients with vitiligo both before and after treatment as well as in 35 controls. Results: Before treatment, serum IL-2 levels in the patients were significantly lower than those in controls (P < 0.01), while the serum IL-4, IFN-γ levels were significantly higher (P < 0.01). After treatment for 6 months, the values were greatly corrected, but remained significantly different from those in controls (P < 0.05). Conclusion: Vitiligo is a kind of auto-immune diseases with abnormal immuno-regulation. (authors)

  1. IL1RL1 gene variants and nasopharyngeal IL1RL-a levels are associated with severe RSV bronchiolitis: a multicenter cohort study.

    Directory of Open Access Journals (Sweden)

    Tina E Faber

    Full Text Available Targets for intervention are required for respiratory syncytial virus (RSV bronchiolitis, a common disease during infancy for which no effective treatment exists. Clinical and genetic studies indicate that IL1RL1 plays an important role in the development and exacerbations of asthma. Human IL1RL1 encodes three isoforms, including soluble IL1RL1-a, that can influence IL33 signalling by modifying inflammatory responses to epithelial damage. We hypothesized that IL1RL1 gene variants and soluble IL1RL1-a are associated with severe RSV bronchiolitis.We studied the association between RSV and 3 selected IL1RL1 single-nucleotide polymorphisms rs1921622, rs11685480 or rs1420101 in 81 ventilated and 384 non-ventilated children under 1 year of age hospitalized with primary RSV bronchiolitis in comparison to 930 healthy controls. Severe RSV infection was defined by need for mechanical ventilation. Furthermore, we examined soluble IL1RL1-a concentration in nasopharyngeal aspirates from children hospitalized with primary RSV bronchiolitis. An association between SNP rs1921622 and disease severity was found at the allele and genotype level (p = 0.011 and p = 0.040, respectively. In hospitalized non-ventilated patients, RSV bronchiolitis was not associated with IL1RL1 genotypes. Median concentrations of soluble IL1RL1-a in nasopharyngeal aspirates were >20-fold higher in ventilated infants when compared to non-ventilated infants with RSV (median [and quartiles] 9,357 [936-15,528] pg/ml vs. 405 [112-1,193] pg/ml respectively; p<0.001.We found a genetic link between rs1921622 IL1RL1 polymorphism and disease severity in RSV bronchiolitis. The potential biological role of IL1RL1 in the pathogenesis of severe RSV bronchiolitis was further supported by high local concentrations of IL1RL1 in children with most severe disease. We speculate that IL1RL1a modifies epithelial damage mediated inflammatory responses during RSV bronchiolitis and thus may serve as a

  2. Closely related glycosylation patterns of recombinant human IL-2 expressed in a CHO cell line and natural IL-2

    International Nuclear Information System (INIS)

    Vita, N.; Magazin, M.; Marchese, E.; Lupker, J.; Ferrara, P.

    1990-01-01

    We report here the study of the glycosylation pattern of human recombinant (r) IL2 expressed in a Chinese hamster ovary (CHO) cell line. The human rIL2 secreted by this high-producing recombinant CHO cell line was metabolically radiolabelled with [35S]-methionine, or with [3H]-glucosamine and [3H]-galactose, purified to homogeneity, and then characterized. The electrophoretic analysis of the [35S]-methionine-labelled proteins present in the culture medium of the CHO cell line showed that the rIL2 represents approximately 12% of the total secreted proteins. Furthermore, pulse-chase experiments showed that the glycosylated rIL2 is synthesized and secreted within 30 min. The point of attachment and the structure of the carbohydrate moiety of the rIL2 was determined by: amino-terminal sequencing and fingerprint analysis of the 3H-labelled rIL2, mass spectroscopy of the amino-terminal tryptic octapeptide, and carbohydrate analysis after enzymatic (Vibrio cholerae neuraminidase and Aspergillus oryzae beta-galactosidase) or sulfuric acid hydrolysis. The results indicate that the recombinant protein possesses a sugar moiety O-linked to the threonine residue at position 3 of the polypeptide chain, and that sialic acid, galactose and N-acetyl galactosamine are components of this carbohydrate moiety. Taken together these results suggest that the recombinant molecule is identical to natural IL2

  3. Data on IL-10R neutralization-induced chronic colitis in Lipocalin 2 deficient mice on BALB/c background

    Directory of Open Access Journals (Sweden)

    Vishal Singh

    2017-04-01

    Full Text Available The data herein is related to the research article entitled “Microbiota-inducible Innate Immune, Siderophore Binding Protein Lipocalin 2 is Critical for Intestinal Homeostasis” (Singh et al., 2016 [1] where we have demonstrated that C57BL/6 Lipocalin 2 deficient mice (Lcn2KO developed chronic colitis upon anti-interleukin-10 receptor (αIL-10R monoclonal antibody administration. In the present article, we evaluated the susceptibility of BALB/c Lcn2KO mice and their WT littermates to the αIL-10R neutralization-induced chronic colitis. Our data showed that αIL-10R mAb-treated BALB/c Lcn2KO mice exhibited severe chronic colitis (i.e., splenomegaly, colomegaly, colonic pathology, and incidence of rectal prolapse when compared to WT mice.

  4. Gene variation in IL-7 receptor (IL-7R)α affects IL-7R response in CD4+ T cells in HIV-infected individuals

    DEFF Research Database (Denmark)

    Hartling, Hans Jakob; Ryder, Lars P.; Ullum, Henrik

    2017-01-01

    Optimal CD4+ T cell recovery after initiating combination antiretroviral treatment (cART) in HIV infection reduces risk of morbidity and mortality. T-allele homozygosity (‘TT’) in the single nucleotide polymorphism, rs6897932(C/T), in the IL-7 receptor α (IL-7RA) is associated with faster CD4+ T...... cell recovery after cART initiation compared to C-allele homozygosity in rs6897932 (‘CC’). However, underlying mechanisms are unknown. We aimed to examine potential mechanisms explaining the association between rs6897932 and CD4+ T cell recovery. Ten ‘TT’ and 10 ‘CC’ HIV-infected individuals matched...... on gender, age, and nadir and current CD4+ T cell counts were included in a cross-sectional study. ‘TT’ individuals had higher proportion of CD4+ T cells expressing pSTAT5 compared to ‘CC’ individuals after stimulating with IL-7, especially when co-stimulated with soluble IL7-RA (sIL-7RA). Furthermore, ‘TT...

  5. Clinical significance of determination of changes of gingival crevicular fluid IL-10, IL-18 and IFN-γLevels in patients periodontitis

    International Nuclear Information System (INIS)

    Chao Rei

    2009-01-01

    Objective: To explore the clinical significance of changes of gingival crevicular fluid levels of interleukin-10 (IL-10), interleukin-18 (IL-18) and interferon-γ were determined with RIA in 42 patients with periodontitis both before and after trentment as well as in 30 controls. Results: Before treatment, the gingival crevicular fluid level of IL-18 and IFN-γ in the patients were significant higher than those in controls (P 0.05). After one month of treatment, the gingival crevigcular fluid levels of IL-18 and IFN-γ were markedly dropped, but remained significantly higher than those in controls (P<0.05). The gingival crevicular fluid levels of IL-10 were markedly dropped, but remained significantly higher than those in controls (P<0.05). The gingival crevicular fluid levels of IL-10 were significant higher than those in controls (P<0.01). The gingival fluid contents of IL-10 and IL-18 were positively correlated with the depth of periodontal pouch and looseness of attachment (r= 0.2617, r= 0.2802, P<0.05) but the interferon-γ contents were negatively correlated (r= -0.1743, P<0.05). Conclusion: The changes of gingival carvacrol fluid levels of interleukin-10, interleukin-18 and If-γ in patients with periodontics suggested that there were disturbances of immunomodulation. (authors)

  6. Clinical significance of determination of levels of several cytokines (IL-1β, IL-2, IL-10 and TNF) in expressed prostatic fluid (EPS) from patients with various types of chronic prostatitis

    International Nuclear Information System (INIS)

    Gao Juxing; Zhang Jiyun

    2006-01-01

    Objective: To investigate the levels of several cytokines in EPS from patients with different types of chronic prostatitis. Methods: The EPS levels of IL-1β, IL-2, IL-10 and TNF were determined with RIA in 86 patients with various types of chronic prostatitis as well as in 30 controls. Results: The EPS levels of IL-1β, IL-2 and TNF in all the 86 patients with various types of chronic prostatitis were significantly higher than those in the controls (P 10/HP, lecithin body < + +) (n=31) were significantly higher than those in patients with CPPS IIIB (WRC < 10/HP, lecithin body normal, n=29)(P<0.05 or P<0.01 ), while the IL-10 levels were significantly lower (P<0.01). Conclusion: EPS levels of the cytokines IL-β, IL-2, TNF and IL-10 might be of value for diagnosis and classification of chronic prostatitis. (authors)

  7. Relations Between Serum Essential Fatty Acids, Cytokines (IL-6 & IL ...

    African Journals Online (AJOL)

    The aim of this study was to investigate the relations between free radical generation, interleukins (IL-6 & IL-8), apoptotic marker soluble Fas (sFas), and the level of ... IL-6, IL-8 and sFas whereas serum fatty acid revealed that Linoleicacid (LA) and alpha linolenic acid (ALA) were significantly decreased in the studied cases .

  8. Twenty-four-hour urinary water-soluble vitamin levels correlate with their intakes in free-living Japanese schoolchildren.

    Science.gov (United States)

    Tsuji, Tomiko; Fukuwatari, Tsutomu; Sasaki, Satoshi; Shibata, Katsumi

    2011-02-01

    To examine the association between 24 h urinary water-soluble vitamin levels and their intakes in free-living Japanese schoolchildren. All foods consumed for four consecutive days were recorded accurately by a weighed food record. A single 24 h urine sample was collected on the fourth day, and the urinary levels of water-soluble vitamins were measured. An elementary school in Inazawa City, Japan. A total of 114 healthy, free-living, Japanese elementary-school children aged 10-12 years. The urinary level of each water-soluble vitamin was correlated positively to its mean intake in the past 2-4 d (vitamin B1: r = 0·42, P vitamin B2: r = 0·43, P vitamin B6: r = 0·49, P vitamin C: r = 0·39, P vitamin B12 (r = 0·10, P = NS). Estimated mean intakes of water-soluble vitamins calculated using urinary levels and recovery rates were 97-102 % of their 3 d mean intake, except for vitamin B12 (79 %). The results show that urinary levels of water-soluble vitamins, except for vitamin B12, reflected their recent intakes in free-living Japanese schoolchildren and could be used as a potential biomarker to estimate mean vitamin intake.

  9. Human amniotic epithelial cells inhibit CD4+ T cell activation in acute kidney injury patients by influencing the miR-101-c-Rel-IL-2 pathway.

    Science.gov (United States)

    Liu, Junfeng; Hua, Rong; Gong, Zhangbin; Shang, Bin; Huang, Yongyi; Guo, Lihe; Liu, Te; Xue, Jun

    2017-01-01

    In the pathogenesis of acute kidney injury (AKI), the release of multiple interleukins can lead to increased kidney damage. Human amniotic epithelial cells (HuAECs) can inhibit immune cell activation in vivo and in vitro. We hypothesized that HuAECs could weaken patient-derived peripheral blood CD4+ T-cell activation and decreasing the ability of these cells to express and release IL-2. -Cell proliferation assay revealed that under the same culture conditions, activated AKI patient-derived CD4+ T cells had a significantly reduced proliferation rate when were co-cultured with HuAECs. And the level of IL-2 released was also significantly reduced. Western blot and qRT-PCR assays showed that the expression of c-Rel in the CD4+ T cells was also significantly reduced. However, the expression level of endogenous miR-101 in the CD4+ T cells co-cultured with HuAECs was significantly increased. Luciferase reporter assay results suggested that miR-101 could bind to a specific site in the c-Rel 3' UTR and induce the post-transcriptional silencing of c-Rel. Subsequently, we over-expressed miR-101 in AKI patient-derived CD4+ T cells. The qRT-PCR and western blot assay results revealed that the expression of endogenous c-Rel was significantly reduced, while the ELISA results indicated that the level of IL-2 released was also significantly decreased. Finally, ChIP-PCR assay results showed that the miR-101-overexpressing CD4+ T-cell group and the HuAEC co-culture CD4+ T-cell group exhibited significantly decreased binding capacities between the 'c-Rel-NFκB' complex and the IL-2 gene promoter, and the transcriptional activity of IL-2 was also significantly decreased. Therefore, we confirmed that HuAECs can stimulate miR-101 expression in AKI patient-derived peripheral blood CD4+ T cells, thus inhibiting the expression of the miR-101 target gene c-Rel and leading to a reduction in IL-2 expression and release. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. The IL23R R381Q gene variant protects against immune-mediated diseases by impairing IL-23-induced Th17 effector response in humans.

    Directory of Open Access Journals (Sweden)

    Paola Di Meglio

    2011-02-01

    Full Text Available IL-23 and Th17 cells are key players in tissue immunosurveillance and are implicated in human immune-mediated diseases. Genome-wide association studies have shown that the IL23R R381Q gene variant protects against psoriasis, Crohn's disease and ankylosing spondylitis. We investigated the immunological consequences of the protective IL23R R381Q gene variant in healthy donors. The IL23R R381Q gene variant had no major effect on Th17 cell differentiation as the frequency of circulating Th17 cells was similar in carriers of the IL23R protective (A and common (G allele. Accordingly, Th17 cells generated from A and G donors produced similar amounts of Th17 cytokines. However, IL-23-mediated Th17 cell effector function was impaired, as Th17 cells from A allele carriers had significantly reduced IL-23-induced IL-17A production and STAT3 phosphorylation compared to G allele carriers. Our functional analysis of a human disease-associated gene variant demonstrates that IL23R R381Q exerts its protective effects through selective attenuation of IL-23-induced Th17 cell effector function without interfering with Th17 differentiation, and highlights its importance in the protection against IL-23-induced tissue pathologies.

  11. The IL23R R381Q gene variant protects against immune-mediated diseases by impairing IL-23-induced Th17 effector response in humans.

    Science.gov (United States)

    Di Meglio, Paola; Di Cesare, Antonella; Laggner, Ute; Chu, Chung-Ching; Napolitano, Luca; Villanova, Federica; Tosi, Isabella; Capon, Francesca; Trembath, Richard C; Peris, Ketty; Nestle, Frank O

    2011-02-22

    IL-23 and Th17 cells are key players in tissue immunosurveillance and are implicated in human immune-mediated diseases. Genome-wide association studies have shown that the IL23R R381Q gene variant protects against psoriasis, Crohn's disease and ankylosing spondylitis. We investigated the immunological consequences of the protective IL23R R381Q gene variant in healthy donors. The IL23R R381Q gene variant had no major effect on Th17 cell differentiation as the frequency of circulating Th17 cells was similar in carriers of the IL23R protective (A) and common (G) allele. Accordingly, Th17 cells generated from A and G donors produced similar amounts of Th17 cytokines. However, IL-23-mediated Th17 cell effector function was impaired, as Th17 cells from A allele carriers had significantly reduced IL-23-induced IL-17A production and STAT3 phosphorylation compared to G allele carriers. Our functional analysis of a human disease-associated gene variant demonstrates that IL23R R381Q exerts its protective effects through selective attenuation of IL-23-induced Th17 cell effector function without interfering with Th17 differentiation, and highlights its importance in the protection against IL-23-induced tissue pathologies.

  12. Chimera of IL-2 Linked to Light Chain of anti-IL-2 mAb Mimics IL-2/anti-IL-2 mAb Complexes Both Structurally and Functionally

    Czech Academy of Sciences Publication Activity Database

    Tomala, Jakub; Kovářová, Jiřina; Kabešová, Martina; Votavová, Petra; Chmelová, Helena; Dvořáková, Barbora; Říhová, Blanka; Kovář, Marek

    2013-01-01

    Roč. 8, č. 5 (2013), s. 871-876 ISSN 1554-8929 R&D Projects: GA ČR GAP301/11/0325 Institutional support: RVO:61388971 Keywords : IN-VIVO EXPANSION * IL-2 * ANTIBODY Subject RIV: CE - Biochemistry Impact factor: 5.356, year: 2013

  13. Levels of 25(OHD3, IL-2, and C-peptide in Children with Type 1 Diabetes Mellitus (T1DM Receiving Vitamin D3 Supplementation

    Directory of Open Access Journals (Sweden)

    Tjahyo Suryanto

    2018-01-01

    Full Text Available Type 1 Diabetes Mellitus (T1DM has become a health problem in many countries. T1DM is the consequence of autoimmune destruction process of β cells. There was relationship between vitamin D deficiency with T1DM. The destruction process was caused by an imbalance of pro-inflammatory and anti-inflammatory cytokines. One of the pro-inflammatory cytokines is IL-2. C-peptide examination to see the function of beta cells due to destruction of pancreatic beta cell. Administration of vitamin D3 supplementation still cause controversy and give varying results. This randomized clinical trial was conducted to determine the levels of 25(OHD3, IL-2, and C-peptide in people with T1DM who received vitamin D3 supplementation. The subjects were 26 children with T1DM, divided into K1 group (received vitamin D3 supplementation and K2 group (received placebo. The results showed higher levels of 25(OHD3 in the K1 group and statistically found a significant difference (p = 0.00. Higher levels of IL-2 and lower C-peptide were obtained in the K1 group and no statistically significant differences were found (p = 0.76 and p= 0.26. The insignificant relationship and the negative correlation were found between 25(OHD3 and IL-2 (p = 0.71; r = - 0.12, 25(OHD3 and C-peptide (p = 0.59; r = -0.16, also levels of IL-2 and C-peptide (p = 0.13; r = -0.44 in children with type 1 diabetes who received vitamin D3 supplementation. From this study can be concluded that administration vitamin D3 supplementation in patients with T1DM can increase levels 25(OHD3 significantly. This increase has not significantly lowered levels of IL-2 and increased levels of C-peptide. However, there was an absolute decrease in the rate of slower C-peptide in the supplemented group than in the placebo group.

  14. The clinical analysis of the TNF-α1 and IL-2 levels in patients with hyperthyroidism

    International Nuclear Information System (INIS)

    Huang Chunling; Zha Jinshun; Jiang Tingyin

    2012-01-01

    Objective: To explore the characters of plasma levels of the tumor necrosis factor-α1 (TNF-α1) and interleukin-2 (IL-2) in patients with hyperthyroidism due to multiple etiologies such as Graves disease (GD) and Hashimoto disease (HD) etc. Methods: Two hundred and fifty hyperthyroidism patients were divided into three groups,including GD group (n=109), HD group (n=80) and other causes of hyperthyroidism group (n=61). Ninety-eight healthy individuals served as control group.The TNF-α1 and IL-2 levels in plasma were measured by radioimmunoassay. Results: The TNF-α1 level in plasma of GD group and HD group were significantly higher than that of other causes of hyperthyroidism group (d TNF-α1 =17.638 and 19.248, both P<0.01) and normal group (d TNF-α1 =24.460 and 26.070, both P<0.01). The IL-2 level in plasma of GD group and HD group were significantly lower than that of other causes of hyperthyroidism group (d IL-2 =2.668 and 2.975, both P<0.01) and normal group (d IL-2 =2.649 and 2.955, both P<0.01).There were no significant differences of the TNF-α1 and IL-2 levels in plasma between other causes of hyperthyroidism group and normal group (d TNF-α1 =0.821, d IL-2 =0.194, both P>0.05). Conclusions: Hyperthyroidism due to autoimmune disease such as GD and HD accompanied with changes of TNF-α1 and IL-2 levels in plasma, while hyperthyroidism due to high iodine uptake, toxic multinodular goiter, and toxic adenoma did not accompany with changes of TNF-α1 and IL-2 levels in plasma. The plasma levels of TNF-α1 and IL-2 may play an important role in differential diagnosis and therapeutic effect evaluation in GD and HD. (authors)

  15. Interleukin (IL)-1 in rat parturition: IL-1 receptors 1 and 2 and accessory proteins abundance in pregnant rat uterus at term - regulation by progesterone.

    Science.gov (United States)

    Ishiguro, Tomohito; Takeda, Jun; Fang, Xin; Bronson, Heather; Olson, David M

    2016-07-01

    The role of interleukin-1 (IL-1), a pro-inflammatory cytokine, in parturition is typically noted by changes in its concentrations. Studying the expression of its receptor family, IL-1 receptor (IL-1R) 1, IL-1R2, IL-1R accessory protein (IL-1RAcP), and its predominantly brain isoform, IL-1RAcPb, during late gestation in the uterus in the Long-Evans rat is another. We assessed changes in their mRNA and protein relative abundance in the uterus and compared IL-1RAcP and IL-1RAcPb mRNA abundance in uterus, cervix, ovaries, placenta, and whole blood of Long-Evans rats during late gestation or in RU486 and progesterone-treated dams using quantitative real-time PCR and western immunoblotting. IL-1R1, IL-1RAcP, and IL-1RAcPb mRNA abundance significantly increased in the uterus at delivery whereas IL-1R2 mRNA abundance significantly decreased. IL-1R1 protein increased at term and IL-1R2 protein decreased at term compared to nonpregnant uteri. IL1-RAcPb mRNA abundance was less than IL-1RAcP, but in the lower uterine segment it was the highest of all tissues examined. RU486 stimulated preterm delivery and an increase in IL-1R1 mRNA abundance whereas progesterone administration extended pregnancy and suppressed the increase in IL-1R1. These data suggest that changes in uterine sensitivity to IL-1 occur during late gestation and suggest another level of regulation for the control of delivery. The roles for IL-1RAcP and IL-1RAcPb need to be determined, but may relate to different intracellular signaling pathways. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  16. Enterovirus 71 antagonizes the antiviral activity of host STAT3 and IL-6R with partial dependence on virus-induced miR-124.

    Science.gov (United States)

    Chang, Zhangmei; Wang, Yan; Bian, Liang; Liu, Qingqing; Long, Jian-Er

    2017-12-01

    Enterovirus 71 (EV71) has caused major outbreaks of hand, foot and mouth disease. EV71 infections increase the production of many host cytokines and pro-inflammatory factors, including interleukin (IL)-6, IL-10 and COX-2. Some of these molecules could stimulate the signal transducer and activator of transcription 3 (STAT3), which plays a key role in regulating host immune responses and several viral diseases. However, the role of STAT3 in EV71 infection remains unknown. This study found that the phosphorylation levels of STAT3 (p Y705 -STAT3) are closely related to EV71 infection. Further experiments revealed that STAT3 exerts an anti-EV71 activity. However, the antiviral activity of STAT3 is partially antagonized by EV71-induced miR-124, which directly targets STAT3 mRNA. Similarly, IL-6R, the α-subunit of the IL-6 receptor complex, exhibits anti-EV71 activity and is directly targeted by the virus-induced miR-124. These results indicate that EV71 can evade host IL-6R- and STAT3-mediated antiviral activities by EV71-induced miR-124. This suggests that controlling miR-124 and the downstream targets, IL-6R and STAT3, might benefit the antiviral treatment of EV71 infection.

  17. Downregulation of IL6 Targeted MiR-376b May Contribute to a Positive IL6 Feedback Loop During Early Liver Regeneration in Mice

    Directory of Open Access Journals (Sweden)

    Shan Lu

    2015-08-01

    Full Text Available Background/Aims: MicroRNAs (miRNAs are a group of endogenous, small, noncoding RNAs implicated in a variety of biological processes, including cell proliferation, apoptosis, differentiation and metabolism. The present study aims to explore the potential role and molecular mechanism of miR-376b during the early phase of liver regeneration. Methods: MiRNA profiling microarrays were used to assess the changes in miRNA expression. For functional analysis, cell proliferation, apoptosis assays, real time quantitative PCR and westernblot analysis were performed. Results: The comprehensive miRNA expression profiling assays on regenerating liver tissues 4 h after partial hepatectomy (PH showed that three miRNAs (miR-127, miR-376b and miR-494 located in the Dlk1-Gtl2 miRNA cluster were significantly downregulated. In vitro functional studies demonstrated that high-level interleukin 6 (IL6 inhibited the expression of miR-376b, and miR-376b mimics treatment decreased cell proliferation and increased apoptosis. Further target analysis showed that miR-376b reduced the mRNA and protein expression levels of NF-kappa-B inhibitor zeta (NFKBIZ and signal transducers and transcription activators 3 (STAT3. Additionally, IL6-induced miR-376b downregulation would, in turn, increase the expression of IL-6 possibly via a feedback loop involving NFKBIZ or/and STAT3. Conclusion: During the early phase of liver regeneration, miR-376b expression was significantly decreased. Our findings reveal that a regulatory circuitry between miR-376b and IL-6 may exist, which trigger the initiation of liver regeneration.

  18. Clinical significance of measurement of plasma leptin and serum IL-6, IL-18 levels after treatment in patients with children nephrotic syndrome

    International Nuclear Information System (INIS)

    Wang Xiaoyan

    2011-01-01

    Objective: To explore the clinical significance of changes of plasma leptin and serum IL-6, IL-18 levels after treatment in patients with children nephrotic syndrome. Methods: Plasma leptin (with RIA) serum IL-6, IL-18 (with ELISA) levels were measured in 31 patients with children nephrotic syndrome both before and after treatment as well as in 30 controls. Results: Before treatment,the plasma leptin and serum IL-6, IL-18 levels were significantly higher than those in controls(P <0.01). After treatment for 3 months, the levels in patients though dropped markedly remained significantly higher than those in controls (P<0.05). Plasma leptin levels were positively correlated with IL-6, IL-18 levels (r=0.6138, 0.5784, P<0.01). Conclusion: Changes of plasma leptin and serum IL-6, IL-18 levels after treatment might be of prognostic importance in patients with children nephrotic syndrome. (authors)

  19. Determinants of IL-6 levels during HIV infection

    DEFF Research Database (Denmark)

    Borges, Alvaro H; O'Connor, Jemma L; Phillips, Andrew N

    2014-01-01

    . MATERIAL AND METHODS: Participants in three international HIV trials (SMART, ESPRIT and SILCAAT) with IL-6 plasma levels measured at baseline were included (N=9864). Factors independently associated with log2-transformed IL-6 level were identified by multivariate linear regression; exponentiated estimates......INTRODUCTION: Elevated IL-6 levels have been linked to increased risk of cardiovascular disease (CVD), cancer and death. Compared to the general population, treated HIV+ persons have 50-100% higher IL-6 levels, but few data on the determinants of IL-6 levels during HIV infection currently exist...

  20. Optically active antifungal azoles. XII. Synthesis and antifungal activity of the water-soluble prodrugs of 1-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1-tetrazolyl)phenyl]-2-imidazolidinone.

    Science.gov (United States)

    Ichikawa, T; Kitazaki, T; Matsushita, Y; Yamada, M; Hayashi, R; Yamaguchi, M; Kiyota, Y; Okonogi, K; Itoh, K

    2001-09-01

    1-[(1R,2R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1-tetrazolyl)phenyl]-2-imidazolidinone (1: TAK-456) was selected as a candidate for clinical trials, but since its water-solubility was insufficient for an injectable formulation, the quaternary triazolium salts 2 were designed as water-soluble prodrugs. Among the prodrugs prepared, 4-acetoxymethyl-1-[(2R,3R)-2-(2,4-difluorophenyl)-2-hydroxy-3-[2-oxo-3-[4-(1H-1-terazolyl)phenyl]-1-imidazolidinyl]butyl]-1H-1,2,4-triazolium chloride (2a: TAK-457) was selected as an injectable candidate for clinical trials based on the results of evaluations on solubility, stability, hemolytic effect and in vivo antifungal activities.

  1. IL-22R Ligands IL-20, IL-22, and IL-24 Promote Wound Healing in Diabetic db/db Mice.

    Science.gov (United States)

    Kolumam, Ganesh; Wu, Xiumin; Lee, Wyne P; Hackney, Jason A; Zavala-Solorio, Jose; Gandham, Vineela; Danilenko, Dimitry M; Arora, Puneet; Wang, Xiaoting; Ouyang, Wenjun

    2017-01-01

    Diabetic foot ulcers (DFU) are one of the major complications in type II diabetes patients and can result in amputation and morbidity. Although multiple approaches are used clinically to help wound closure, many patients still lack adequate treatment. Here we show that IL-20 subfamily cytokines are upregulated during normal wound healing. While there is a redundant role for each individual cytokine in this subfamily in wound healing, mice deficient in IL-22R, the common receptor chain for IL-20, IL-22, and IL-24, display a significant delay in wound healing. Furthermore, IL-20, IL-22 and IL-24 are all able to promote wound healing in type II diabetic db/db mice. Mechanistically, when compared to other growth factors such as VEGF and PDGF that accelerate wound healing in this model, IL-22 uniquely induced genes involved in reepithelialization, tissue remodeling and innate host defense mechanisms from wounded skin. Interestingly, IL-22 treatment showed superior efficacy compared to PDGF or VEGF in an infectious diabetic wound model. Taken together, our data suggest that IL-20 subfamily cytokines, particularly IL-20, IL-22, and IL-24, might provide therapeutic benefit for patients with DFU.

  2. Development of a quantitative bead capture assay for soluble IL-7 receptor alpha in human plasma.

    Directory of Open Access Journals (Sweden)

    Sylvie Faucher

    Full Text Available BACKGROUND: IL-7 is an essential cytokine in T-cell development and homeostasis. It binds to the IL-7R receptor, a complex of the IL-7Ralpha (CD127 and common gamma (CD132 chains. There is significant interest in evaluating the expression of CD127 on human T-cells as it often decreased in medical conditions leading to lymphopenia. Previous reports showed the usefulness of CD127 as a prognostic marker in viral infections such as HIV, CMV, EBV and HCV. A soluble CD127 (sCD127 is released in plasma and may contribute to disease pathogenesis through its control on IL-7 activities. Measuring sCD127 is important to define its role and may complement existing markers used in lymphopenic disease management. We describe a new quantitative assay for the measurement of sCD127 in plasma and report sCD127 concentrations in healthy adults. METHODOLOGY/PRINCIPAL FINDINGS: We developed a quantitative bead-based sCD127 capture assay. Polyclonal CD127-specific antibodies were chosen for capture and a biotinylated monoclonal anti-CD127 antibody was selected for detection. The assay can detect native sCD127 and recombinant sCD127 which served as the calibrator. The analytical performance of the assay was characterized and the concentration and stability of plasma sCD127 in healthy adults was determined. The assay's range was 3.2-1000 ng/mL. The concentration of plasma sCD127 was 164+/-104 ng/mL with over a log variation between subjects. Individual sCD127 concentrations remained stable when measured serially during a period of up to one year. CONCLUSIONS/SIGNIFICANCE: This is the first report on the quantification of plasma sCD127 in a population of healthy adults. Soluble CD127 plasma concentrations remained stable over time in a given individual and sCD127 immunoreactivity was resistant to repeated freeze-thaw cycles. This quantitative sCD127 assay is a valuable tool for defining the potential role of sCD127 in lymphopenic diseases.

  3. High soluble CD30, CD25 and IL-6 may identify patients with worse survival in CD30+ cutaneous lymphomas and early mycosis fungoides

    Science.gov (United States)

    Kadin, Marshall E.; Pavlov, Igor; Delgado, Julio C.; Vonderheid, Eric C.

    2011-01-01

    Histopathology alone cannot predict outcome of patients with CD30+ primary cutaneous lymphoproliferative disorders (CD30CLPD) and early mycosis fungoides (MF). To test the hypothesis that serum cytokines/cytokine receptors provide prognostic information in these disorders, we measured soluble CD30 (sCD30), sCD25, and selected cytokines in cell cultures and sera of 116 patients with CD30CLPD and 96 patients with early MF followed up to 20 years. Significant positive correlation was found between sCD30 levels and sCD25, CD40L, IL-6, and IL-8, suggesting CD30+ neoplastic cells secrete these cytokines, but not Th2 cytokines. In vitro studies confirmed sCD30, sCD25, IL-6 and IL-8 are secreted by CD30CLPD-derived cell lines. CD30CLPD patients with above normal sCD30 and sCD25 had worse overall and disease-related survivals, but only sCD30 retained significance in Cox models that included advanced age. High sCD30 also identified patients with worse survival in early MF. Increased IL-6 and IL-8 correlated with poor disease-related survival in CD30CLPD patients, We conclude that: (1) neoplastic cells of some CD30CLPD patients do not resemble Th2 cells, (2) high serum sCD30, sCD25, IL-6, and perhaps IL-8 levels may provide prognostic information useful for patient management. PMID:22071475

  4. IL-23 Promotes Myocardial I/R Injury by Increasing the Inflammatory Responses and Oxidative Stress Reactions

    Directory of Open Access Journals (Sweden)

    Xiaorong Hu

    2016-05-01

    Full Text Available Background/Aims: Inflammation and oxidative stress play an important role in myocardial ischemia and reperfusion (I/R injury. We hypothesized that IL-23, a pro-inflammatory cytokine, could promote myocardial I/R injury by increasing the inflammatory response and oxidative stress. Methods: Male Sprague-Dawley rats were randomly assigned into sham operated control (SO group, ischemia and reperfusion (I/R group, (IL-23 + I/R group and (anti-IL-23 + I/R group. At 4 h after reperfusion, the serum concentration of lactate dehydrogenase (LDH, creatine kinase (CK and the tissue MDA concentration and SOD activity were measured. The infarcte size was measured by TTC staining. Apoptosis in heart sections were measured by TUNEL staining. The expression of HMGB1 and IL-17A were detected by Western Blotting and the expression of TNF-α and IL-6 were detected by Elisa. Results: After 4 h reperfusion, compared with the I/R group, IL-23 significantly increased the infarct size, the apoptosis of cardiomyocytes and the levels of LDH and CK (all P 0.05. All these effects were abolished by anti-IL-23 administration. Conclusion: The present study suggested that IL-23 may promote myocardial I/R injury by increasing the inflammatory responses and oxidative stress reaction.

  5. IL-2 induction of IL-1 beta mRNA expression in monocytes. Regulation by agents that block second messenger pathways

    DEFF Research Database (Denmark)

    Kovacs, E J; Brock, B; Varesio, L

    1989-01-01

    We have previously shown that in mixed cultures of PBL incubation with human rIL-2 induces the rapid expression of IL-1 alpha and IL-1 beta mRNA. Because studies have demonstrated that IL-2R can be expressed on the surface of human peripheral blood monocytes, we chose to investigate whether IL-1 ...

  6. IL-5 and IL-5 receptor in asthma

    Directory of Open Access Journals (Sweden)

    ATC Kotsimbos

    1997-12-01

    Full Text Available Eosinophils, along with mast cells are key cells involved in the innate immune response against parasitic infection whereas the adaptive immune response is largely dependent on lymphocytes. In chronic parasitic disease and in chronic allergic disease, IL-5 is predominantly a T cell derived cytokine which is particularly important for the terminal differentiation, activation and survival of committed eosinophil precursors. The human IL-5 gene is located on chromosome 5 in a gene cluster that contains the evolutionary related IL-4 family of cytokine genes. The human IL-5 receptor complex is a heterodimer consisting of a unique a subunit (predominantly expressed on eosinophils and a beta subunit which is shared between the receptors for IL-3 & GM-CSF (more widely expressed. The a subunit is required for ligand-specific binding whereas association with the beta subunit results in increased binding affinity. The alternative splicing of the alphaIL-5R gene which contains 14 exons can yield several alphaIL-5R isoforms including a membrane-anchored isoform (alphaIL-5Rm and a soluble isoform (alphaIL-5Rs. Cytokines such as IL-5 produce specific and non-specific cellular responses through specific cell membrane receptor mediated activation of intracellular signal transduction pathways which, to a large part, regulate gene expression. The major intracellular signal transduction mechanism is activation of non-receptor associated tyrosine kinases including JAK and MAP kinases which can then transduce signals via a novel family of transcriptional factors named signal transducers and activators of transcription (STATS. JAK2, STAT1 and STAT 5 appear to be particularly important in IL-5 mediated eosinophil responses. Asthma is characterized by episodic airways obstruction, increased bronchial responsiveness, and airway inflammation. Several studies have shown an association between the number of activated T cells and eosinophils in the airways and abnormalities

  7. Serial measurement of the circulating levels of tumour necrosis factor and its soluble receptors 1 and 2 for monitoring leprosy patients during multidrug treatment

    Directory of Open Access Journals (Sweden)

    Rosane Dias Costa

    2013-12-01

    Full Text Available Leprosy is an infectious and contagious spectral disease accompanied by a series of immunological events triggered by the host response to the aetiologic agent, Mycobacterium leprae . The induction and maintenance of the immune/inflammatory response in leprosy are linked to multiple cell interactions and soluble factors, primarily through the action of cytokines. The purpose of the present study was to evaluate the serum levels of tumour necrosis factor (TNF-α and its soluble receptors (sTNF-R1 and sTNF-R2 in leprosy patients at different stages of multidrug treatment (MDT in comparison with non-infected individuals and to determine their role as putative biomarkers of the severity of leprosy or the treatment response. ELISA was used to measure the levels of these molecules in 30 healthy controls and 37 leprosy patients at the time of diagnosis and during and after MDT. Our results showed increases in the serum levels of TNF-α and sTNF-R2 in infected individuals in comparison with controls. The levels of TNF-α, but not sTNF-R2, decreased with treatment. The current results corroborate previous reports of elevated serum levels of TNF-α in leprosy and suggest a role for sTNF-R2 in the control of this cytokine during MDT.

  8. Inflammatory reactions in placental blood of Plasmodium falciparum-infected women and high concentrations of soluble E-selectin and a circulating P. falciparum protein in the cord sera

    DEFF Research Database (Denmark)

    Jakobsen, P H; Rasheed, F N; Bulmer, J N

    1998-01-01

    concentrations measured in the placenta. Markers of inflammatory reactions: IL-10, sIL-2R, sIL-4R, and soluble tumour necrosis factor receptor I (sTNF-RI) were found in high concentrations in the placenta, indicating that inflammatory reactions take place in the placenta which has been regarded...... as an immunoprivileged site. Concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intracellular adhesion molecule-1 (sICAM-1), potential adhesion receptors for malaria parasites, were associated with an active P. falciparum infection in the placenta although the associations did not reach...

  9. Evaluating ESWL-induced renal injury based on urinary TNF-α, IL-1α, and IL-6 levels.

    Science.gov (United States)

    Goktas, Cemal; Coskun, Abdurrahman; Bicik, Zerrin; Horuz, Rahim; Unsal, Ibrahim; Serteser, Mustafa; Albayrak, Selami; Sarıca, Kemal

    2012-10-01

    Extracorporeal shockwave lithotripsy (ESWL) has dramatically changed the treatment of urinary lithiasis and has been the first treatment option for the majority of patients for more than two decades. Despite its significant benefits, it induces acute renal injury that extends from the papilla to the outer cortex. We evaluated the severity of the inflammatory response to ESWL by measuring the urinary excretion of the cytokines TNF-α, IL-1α, and IL-6. The study included 21 selected patients and 14 control subjects. All patients underwent the same ESWL procedure (2,500 shockwaves at 100 shockwaves/min and 0.039 J from the lithotripter). Urine TNF-α, IL-1α, and IL-6 levels were measured using standard ELISA kits. In the study population (patients and controls), we did not detect TNF-α in the urine samples. The levels of both IL-1α (2.5 pg/ml) and IL-6 (3.8 pg/ml) measured before ESWL were not significantly different from the control group (2.5 and 5.2 pg/ml, respectively; p > 0.05). Twenty-four hours after ESWL, in contrast to IL-1α (4 pg/ml), urine IL-6 (19.7 pg/ml) increased significantly (p ESWL, IL-1α increased to 5 pg/ml, while IL-6 (7 pg/ml) decreased to the control level. Urine cytokine levels may be used to evaluate the inflammatory response to ESWL. After ESWL, IL-6 levels increased in the early phase, while IL-1α levels increased later. These two markers may be used to measure the severity of inflammation. In contrast to IL-1α and IL-6, urine TNF-α excretion was not increased by ESWL. We believe that the inflammatory response to ESWL can be detected by the urinary excretion of IL-1α for up to 14 days.

  10. Study on changes of serum leptin, IGF-I and IL-2 levels in elderly subjects with osteoporosis

    International Nuclear Information System (INIS)

    Sun Zihan; Luo Nanping; Niu Aijun; Qi Falian

    2006-01-01

    Objective: To investigate the changes of serum leptin, IGF-I and IL-2 levels in elderly subjects with osteoporosis. Methods: Serum leptin, IGF-I, IL-2 levels (with RIA), total cholesterol contents (with biochemical method) and bone mineral density (BMD) were examined in 65 aged patients with osteoporosis. Results: The serum leptin levels in subjects with osteoporosis were significantly higher than controls (P<0.01). The serum IGF-I and IL-2 levels in subjects with osteoporosis were significantly lower than those in controls (P<0.05, P<0.01). The BMD was positively correlated with the IGF-I levels and negatively correlated with leptin level. Conclusion: Derangement of leptin and IGF-I, IL-2 metabolism is one of the major causes of decreased bone mass and bone formation elderly subjects with osteoporosis. Measurement of serum levels of these parameters is of diagnostic help. (authors)

  11. Therapeutic Targeting of the IL-6 Trans-Signaling/Mechanistic Target of Rapamycin Complex 1 Axis in Pulmonary Emphysema.

    Science.gov (United States)

    Ruwanpura, Saleela M; McLeod, Louise; Dousha, Lovisa F; Seow, Huei J; Alhayyani, Sultan; Tate, Michelle D; Deswaerte, Virginie; Brooks, Gavin D; Bozinovski, Steven; MacDonald, Martin; Garbers, Christoph; King, Paul T; Bardin, Philip G; Vlahos, Ross; Rose-John, Stefan; Anderson, Gary P; Jenkins, Brendan J

    2016-12-15

    The potent immunomodulatory cytokine IL-6 is consistently up-regulated in human lungs with emphysema and in mouse emphysema models; however, the mechanisms by which IL-6 promotes emphysema remain obscure. IL-6 signals using two distinct modes: classical signaling via its membrane-bound IL-6 receptor (IL-6R), and trans-signaling via a naturally occurring soluble IL-6R. To identify whether IL-6 trans-signaling and/or classical signaling contribute to the pathogenesis of emphysema. We used the gp130 F/F genetic mouse model for spontaneous emphysema and cigarette smoke-induced emphysema models. Emphysema in mice was quantified by various methods including in vivo lung function and stereology, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to assess alveolar cell apoptosis. In mouse and human lung tissues, the expression level and location of IL-6 signaling-related genes and proteins were measured, and the levels of IL-6 and related proteins in sera from emphysematous mice and patients were also assessed. Lung tissues from patients with emphysema, and from spontaneous and cigarette smoke-induced emphysema mouse models, were characterized by excessive production of soluble IL-6R. Genetic blockade of IL-6 trans-signaling in emphysema mouse models and therapy with the IL-6 trans-signaling antagonist sgp130Fc ameliorated emphysema by suppressing augmented alveolar type II cell apoptosis. Furthermore, IL-6 trans-signaling-driven emphysematous changes in the lung correlated with mechanistic target of rapamycin complex 1 hyperactivation, and treatment of emphysema mouse models with the mechanistic target of rapamycin complex 1 inhibitor rapamycin attenuated emphysematous changes. Collectively, our data reveal that specific targeting of IL-6 trans-signaling may represent a novel treatment strategy for emphysema.

  12. The distribution of IL-13 receptor alpha1 expression on B cells, T cells and monocytes and its regulation by IL-13 and IL-4.

    Science.gov (United States)

    Graber, P; Gretener, D; Herren, S; Aubry, J P; Elson, G; Poudrier, J; Lecoanet-Henchoz, S; Alouani, S; Losberger, C; Bonnefoy, J Y; Kosco-Vilbois, M H; Gauchat, J F

    1998-12-01

    To study the expression of IL-13 receptor alpha1 (IL-13Ralpha1), specific monoclonal antibodies (mAb) were generated. Surface expression of the IL-13Ralpha1 on B cells, monocytes and T cells was assessed by flow cytometry using these specific mAb. Among tonsillar B cells, the expression was the highest on the IgD+ CD38- B cell subpopulation which is believed to represent naive B cells. Expression was also detectable on a large fraction of the IgD-CD38- B cells but not on CD38+ B cells. Activation under conditions which promote B cell Ig class switching up-regulated the expression of the receptor. However, the same stimuli had an opposite effect for IL-13Ralpha1 expression levels on monocytes. While IL-13Ralpha1 mRNA was clearly detectable in T cell preparations, no surface expression was detected. However, permeabilization of the T cells showed a clear intracellular expression of the receptor. A soluble form of the receptor was immunoprecipitated from the supernatant of activated peripheral T cells, suggesting that T cell IL-13Ralpha1 might have functions unrelated to the capacity to form a type II IL-4/IL-13R with IL-4Ralpha.

  13. Cytokines, chemokines and soluble adhesion molecules in aqueous humor of children with uveitis.

    Science.gov (United States)

    Sijssens, Karen M; Rijkers, Ger T; Rothova, Aniki; Stilma, Jan S; Schellekens, Peter A W J F; de Boer, Joke H

    2007-10-01

    Uveitis in childhood is a visual threatening disease with a complication rate of more than 75%. Despite extensive research, the etiology of uveitis is still unclear although the general opinion is now that uveitis is a T-cell mediated disease. The purpose of this study was to investigate the profile of cytokines, chemotactic cytokines (chemokines) and soluble adhesion molecules in the aqueous humor (AqH) of children with uveitis in order to identify the factors that control the immune response in the eye. In this clinical laboratory investigation we analyzed, with a multiplex immunoassay, 16 immune mediators in the AqH of 25 children with uveitis and 6 children without uveitis. Increased levels of interleukin-2 (IL-2), IL-6, IL-10, IL-13, IL-18, interferon-gamma, tumor necrosis factor-alpha, soluble intercellular adhesion molecule-1, RANTES, IL-8 and interferon-inducible 10-kDa protein were found in the AqH of children with uveitis compared with controls. No significant differences were found for IL-1 beta, IL-4, IL-12 p-70, soluble vascular cell adhesion molecule 1 and Eotaxin. Lower levels of IL-10 and IL-8 were found in quiet stage uveitis (surgical) samples compared with active uveitis (diagnostic) samples and in samples of patients treated with methotrexate (MTX) compared with samples of patients not treated with MTX. Lower levels of IL-10 were as well found in samples taken during the first 3 months after the diagnosis of uveitis than samples taken later during the disease process. No significant differences were found between patients treated with or without topical or systemic (perioperative and long term) corticosteroids. In conclusion, in children with uveitis, multiple intraocular cytokines, chemokines and soluble adhesion molecules are increased in the AqH regardless of active or inactive inflammation. Whether the IL-8 and IL-10 levels in AqH of children with uveitis are correlated with uveitis activity, early or late phase of the course of the disease

  14. Postoperative changes in serum cytokines profile and nitric oxide levels in patients with cystic echinococcosis

    Directory of Open Access Journals (Sweden)

    Refik M.

    2005-09-01

    Full Text Available The aim of the present study was to examine serum cytokines and nitric oxide (NO levels in patients with cystic echinococcosis (CE. 28 patients with CE were studied and all underwent surgery. Serum levels of tumour necrosis factor-alpha (TNF-α, interleukin IL- 1β, receptor of soluble IL-2R (sIL-2R, IL-6, IL-8, nitrate/nitrite, and C-reactive protein (CRP were determined before and after induction of treatment. Data were compared with those obtained from 28 healthy volunteers. IL-6 was elevated in all CE patients (100%. IL-8 was increased in 11/28 (39.3%. Increased levels of IL-2R and TNF-α were found in a limited number of them particularly those showing cysts in the central area of the liver (5/28, 6/28. IL-1β level was not elevated in any patient except in secondary severe CE. CRP and nitrate/nitrite levels were also increased. A positive correlation between CRP and IL-6 (r = 0.74; p < 0.001 was found confirming the link between inflammation due to CE and activation of monocytes. All patients completely recovered and the levels of the studied parameters reverted to normal levels except one patient in whom severe recurrent disease occurred two years after the first operation. These results suggest that there are different immunoregulatory events and cytokines response during CE and may be in part related to slight monocytosis and in part to Th2 activation. IL-6, NO and CRP were unambiguously involved in the host parasite interaction and therefore may be useful markers in monitoring CE management and evaluating surgical stress.

  15. Silencing of microRNA-138-5p promotes IL-1β-induced cartilage degradation in human chondrocytes by targeting FOXC1: miR-138 promotes cartilage degradation.

    Science.gov (United States)

    Yuan, Y; Zhang, G Q; Chai, W; Ni, M; Xu, C; Chen, J Y

    2016-10-01

    Osteoarthritis (OA) is characterised by articular cartilage degradation. MicroRNAs (miRNAs) have been identified in the development of OA. The purpose of our study was to explore the functional role and underlying mechanism of miR-138-5p in interleukin-1 beta (IL-1β)-induced extracellular matrix (ECM) degradation of OA cartilage. Human articular cartilage was obtained from patients with and without OA, and chondrocytes were isolated and stimulated by IL-1β. The expression levels of miR-138-5p in cartilage and chondrocytes were both determined. After transfection with miR-138-5p mimics, allele-specific oligonucleotide (ASO)-miR-138-5p, or their negative controls, the messenger RNA (mRNA) levels of aggrecan (ACAN), collagen type II and alpha 1 (COL2A1), the protein levels of glycosaminoglycans (GAGs), and both the mRNA and protein levels of matrix metalloproteinase (MMP)-13 were evaluated. Luciferase reporter assay, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot were performed to explore whether Forkhead Box C1 (FOCX1) was a target of miR-138-5p. Further, we co-transfected OA chondrocytes with miR-138-5p mimics and pcDNA3.1 (+)-FOXC1 and then stimulated with IL-1β to determine whether miR-138-5p-mediated IL-1β-induced cartilage matrix degradation resulted from targeting FOXC1. MiR-138-5p was significantly increased in OA cartilage and in chondrocytes in response to IL-1β-stimulation. Overexpression of miR-138-5p significantly increased the IL-1β-induced downregulation of COL2A1, ACAN, and GAGs, and increased the IL-1β-induced over expression of MMP-13.We found that FOXC1 is directly regulated by miR-138-5p. Additionally, co-transfection with miR-138-5p mimics and pcDNA3.1 (+)-FOXC1 resulted in higher levels of COL2A1, ACAN, and GAGs, but lower levels of MMP-13. miR-138-5p promotes IL-1β-induced cartilage degradation in human chondrocytes, possibly by targeting FOXC1.Cite this article: Y. Yuan, G. Q. Zhang, W. Chai,M. Ni, C. Xu, J

  16. Raised IL-6 Levels

    African Journals Online (AJOL)

    user

    Cardiovascular Associated Complications in HIV. Positive Zambians before ... compare plasma levels of IL-6 in HIV positive and. HIV negative .... cancer. Results from this study showed that IL-6 levels in. HIV positive ART naive individuals were significantly higher than in the HIV positive individuals on ART. Our findings ...

  17. Elevated serum IL-10 levels in diffuse large B-cell lymphoma: a mechanism of aberrant JAK2 activation.

    Science.gov (United States)

    Gupta, Mamta; Han, Jing Jing; Stenson, Mary; Maurer, Matthew; Wellik, Linda; Hu, Guangzhen; Ziesmer, Steve; Dogan, Ahmet; Witzig, Thomas E

    2012-03-22

    Cytokines are deregulated in cancers and can contribute to tumor growth. In patients with diffuse large-cell lymphoma (DLBCL), we observed higher levels of JAK/STAT pathway-related serum cytokines (ie, IL-6, IL-10, epidermal growth factor, and IL-2) compared with controls. Of these, only IL-10 activated the JAK2 pathway in lymphoma cells in vitro. Patients with high serum IL-10 had shorter event-free survival (EFS) than patients with low levels (P > .01) and high IL-10 was correlated with high lactase dehydrogenase (P = .0085) and higher International Prognostic Index scores (P = .01). To explore the mechanism by which IL-10 may contribute to an inferior EFS, we investigated the effect of IL-10 on the JAK2 pathway and found that the IL-10/IL-10 receptor complex up-regulated JAK2 signaling. Neutralizing Ab to IL-10 inhibited constitutive and IL-10-induced JAK2/STAT3 phosphorylation. JAK2 inhibition dephosphorylated JAK2 and STAT3 and caused an inhibitory effect on phospho-JAK2-positive DLBCL cells; there was a minimal effect on phospho-JAK2-negative cells. Apoptosis induced by JAK2 inhibition was dependent on inhibition of autocrine IL-10 and c-myc expression and independent of Bcl-2 family expression. These results provide the rationale for testing JAK2 inhibitors in DLBCL patients, and indicate that serum IL-10 may be a biomarker to identify patients more likely to respond to JAK2-targeted therapy.

  18. Expression of IL-18, IL-18 Binding Protein, and IL-18 Receptor by Normal and Cancerous Human Ovarian Tissues: Possible Implication of IL-18 in the Pathogenesis of Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    Liat Medina

    2014-01-01

    Full Text Available Proinflammatory cytokine IL-18 has been shown to be elevated in the sera of ovarian carcinoma patients. The aim of the study was to examine the levels and cellular origin of IL-18, IL-18 binding protein, and IL-18 receptor in normal and cancerous ovarian tissues. Ovarian tissue samples were examined by immunohistochemical staining for IL-18, IL-18BP, and IL-18R and mRNA of these cytokines was analyzed with semiquantitative PT-PCR. IL-18 levels were significantly higher in cancerous ovarian tissues (P=0.0007, IL-18BP levels were significantly higher in normal ovarian tissues (P=0.04, and the ratio of IL-18/IL-18BP was significantly higher in cancerous ovarian tissues (P=0.036. Cancerous ovarian tissues expressed significantly higher IL-18 mRNA levels (P=0.025, while there was no difference in the expression of IL-18BP mRNA and IL-18R mRNA between cancerous and normal ovarian tissues. IL-18 and IL-18BP were expressed dominantly in the epithelial cells of both cancerous and normal ovarian tissues, while IL-18R was expressed dominantly in the epithelial cells of cancerous ovarian tissues but expressed similarly in the epithelial and stromal cells of normal cancerous tissues. This study indicates a possible role of IL-18, IL-18BP, and IL-18R in the pathogenesis of epithelial ovarian carcinoma.

  19. IL-13 induces a bronchial epithelial phenotype that is profibrotic

    Directory of Open Access Journals (Sweden)

    Dinh Bao T

    2008-03-01

    Full Text Available Abstract Background Inflammatory cytokines (e.g. IL-13 and mechanical perturbations (e.g. scrape injury to the epithelium release profibrotic factors such as TGF-β2, which may, in turn, stimulate subepithelial fibrosis in asthma. We hypothesized that prolonged IL-13 exposure creates a plastic epithelial phenotype that is profibrotic through continuous secretion of soluble mediators at levels that stimulate subepithelial fibrosis. Methods Normal human bronchial epithelial cells (NHBE were treated with IL-13 (0, 0.1, 1, or 10 ng/ml for 14 days (day 7 to day 21 following seeding at an air-liquid interface during differentiation, and then withdrawn for 1 or 7 days. Pre-treated and untreated NHBE were co-cultured for 3 days with normal human lung fibroblasts (NHLF embedded in rat-tail collagen gels during days 22–25 or days 28–31. Results IL-13 induced increasing levels of MUC5AC protein, and TGF-β2, while decreasing β-Tubulin IV at day 22 and 28 in the NHBE. TGF-β2, soluble collagen in the media, salt soluble collagen in the matrix, and second harmonic generation (SHG signal from fibrillar collagen in the matrix were elevated in the IL-13 pre-treated NHBE co-cultures at day 25, but not at day 31. A TGF-β2 neutralizing antibody reversed the increase in collagen content and SHG signal. Conclusion Prolonged IL-13 exposure followed by withdrawal creates an epithelial phenotype, which continuously secretes TGF-β2 at levels that increase collagen secretion and alters the bulk optical properties of an underlying fibroblast-embedded collagen matrix. Extended withdrawal of IL-13 from the epithelium followed by co-culture does not stimulate fibrosis, indicating plasticity of the cultured airway epithelium and an ability to return to a baseline. Hence, IL-13 may contribute to subepithelial fibrosis in asthma by stimulating biologically significant TGF-β2 secretion from the airway epithelium.

  20. IL-6 amplifies TLR mediated cytokine and chemokine production: implications for the pathogenesis of rheumatic inflammatory diseases.

    Directory of Open Access Journals (Sweden)

    Ivan Caiello

    Full Text Available The role of Interleukin(IL-6 in the pathogenesis of joint and systemic inflammation in rheumatoid arthritis (RA and systemic juvenile idiopathic arthritis (s-JIA has been clearly demonstrated. However, the mechanisms by which IL-6 contributes to the pathogenesis are not completely understood. This study investigates whether IL-6 affects, alone or upon toll like receptor (TLR ligand stimulation, the production of inflammatory cytokines and chemokines in human peripheral blood mononuclear cells (PBMCs, synovial fluid mononuclear cells from JIA patients (SFMCs and fibroblast-like synoviocytes from rheumatoid arthritis patients (RA synoviocytes and signalling pathways involved. PBMCs were pre-treated with IL-6 and soluble IL-6 Receptor (sIL-6R. SFMCs and RA synoviocytes were pre-treated with IL-6/sIL-6R or sIL-6R, alone or in combination with Tocilizumab (TCZ. Cells were stimulated with LPS, S100A8-9, poly(I-C, CpG, Pam2CSK4, MDP, IL-1β. Treatment of PBMCs with IL-6 induced production of TNF-α, CXCL8, and CCL2, but not IL-1β. Addition of IL-6 to the same cells after stimulation with poly(I-C, CpG, Pam2CSK4, and MDP induced a significant increase in IL-1β and CXCL8, but not TNF-α production compared with TLR ligands alone. This enhanced production of IL-1β and CXCL8 paralleled increased p65 NF-κB activation. In contrast, addition of IL-6 to PBMCs stimulated with LPS or S100A8-9 (TLR-4 ligands led to reduction of IL-1β, TNF-α and CXCL8 with reduced p65 NF-κB activation. IL-6/IL-1β co-stimulation increased CXCL8, CCL2 and IL-6 production. Addition of IL-6 to SFMCs stimulated with LPS or S100A8 increased CXCL8, CCL2 and IL-1β production. Treatment of RA synoviocytes with sIL-6R increased IL-6, CXCL8 and CCL2 production, with increased STAT3 and p65 NF-κB phosphorylation. Our results suggest that IL-6 amplifies TLR-induced inflammatory response. This effect may be relevant in the presence of high IL-6 and sIL-6R levels, such as in arthritic

  1. Correlation between high blood IL-6 level, hyperglycemia, and glucose control in septic patients.

    Science.gov (United States)

    Nakamura, Masataka; Oda, Shigeto; Sadahiro, Tomohito; Watanabe, Eizo; Abe, Ryuzo; Nakada, Taka-Aki; Morita, Yasumasa; Hirasawa, Hiroyuki

    2012-12-12

    The aim of the present study was to investigate the relationship between the blood IL-6 level, the blood glucose level, and glucose control in septic patients. This retrospective observational study in a general ICU of a university hospital included a total of 153 patients with sepsis, severe sepsis, or septic shock who were admitted to the ICU between 2005 and 2010, stayed in the ICU for 7 days or longer, and did not receive steroid therapy prior to or after ICU admission. The severity of stress hyperglycemia, status of glucose control, and correlation between those two factors in these patients were investigated using the blood IL-6 level as an index of hypercytokinemia. A significant positive correlation between blood IL-6 level and blood glucose level on ICU admission was observed in the overall study population (n = 153; r = 0.24, P = 0.01), and was stronger in the nondiabetic subgroup (n = 112; r = 0.42, P glucose control (blood glucose level blood IL-6 level on ICU admission (P blood IL-6 level after ICU admission remained significantly higher and the 60-day survival rate was significantly lower in the failed glucose control group than in the successful glucose control group (P blood IL-6 level was correlated with hyperglycemia and with difficulties in glucose control in septic patients. These results suggest the possibility that hypercytokinemia might be involved in the development of hyperglycemia in sepsis, and thereby might affect the success of glucose control.

  2. Release of soluble CD30 after allogeneic stimulation is mediated by memory T cells and regulated by IFN-γ and IL-2.

    Science.gov (United States)

    Velásquez, Sonia Y; García, Luis F; Opelz, Gerhard; Alvarez, Cristiam M; Süsal, Caner

    2013-07-27

    Membrane CD30 is an important costimulatory molecule for activated T lymphocytes, and serum level of soluble CD30 (sCD30) is considered a marker for predicting outcome in kidney transplantation. We investigated the kinetics of CD30 expression on CD4 and CD8 T-cell populations and the source of sCD30 during alloimmune responses in vitro. The effect of neutralizing antibodies against interferon (IFN)-γ and other cytokines on sCD30 release and the involvement of metalloproteinases ADAM10 and ADAM17/TACE that are responsible for sCD30 shedding were also assessed. Memory phenotypes and CD30 expression on allostimulated CD3 lymphocytes were evaluated in dialysis patients and matched controls. Allogeneic stimulation resulted in conversion of naive responder cells to central memory CD4 cells (PCD30 expression. Release of sCD30 was attributed mainly to central memory cells, and neutralization of IFN-γ (PsCD30 during allostimulation but did not alter the levels of ADAM10 and ADAM17/TACE. CD30 expression was modulated in dialysis patients in a similar way as in healthy controls. Allostimulation results in the up-regulation of the T-cell activation marker CD30 on CD4 as well as CD8 memory T cells and increased release of sCD30 from these cells in an IFN-γ- and IL-2-dependent manner. These results may explain clinical findings on the suitability of sCD30 and IFN-γ- and IL-2-producing T cells for immune monitoring of kidney transplant recipients before and after transplantation.

  3. IL18 and IL18R1 polymorphisms, lung CT and fibrosis: a longitudinal study in coal miners

    Energy Technology Data Exchange (ETDEWEB)

    Nadif, R.; Mintz, M.; Marzec, J.; Jedlicka, A.; Kauffmann, F.; Kleeberger, S.R. [INSERM, U780, Villejuif (France)

    2006-12-15

    It has been suggested that interleukin (IL)-18 plays a role in the development of inflammatory and fibrosing lung diseases. Associations of polymorphisms in the genes coding for IL-18 (108 /G-656T, C-607A, G-137C, T113G, C127T) and its receptor (IL8R1/C-69T) with coal workers' pneumoconiosis (CWP) were studied in 200 miners who were examined in 1990, 1994 and 1999. Coal-dust exposure was assessed according to job history and ambient measures. The main health outcome was lung computed tomography (CT) score in 1990. Internal coherence was assessed by studying CT score in 1994, 4-yr change in CT score and CWP incidence and prevalence. CT score in 1990 was a good predictor of radiographic grade in 1999 and, therefore, an appropriate subclinical quantitative trait. The IL18 -137C allele was associated with lower CT score in 1990 and 1994 (11.24 versus 1.69 and 1.57 versus 2.46, respectively), slower progression of CT score between 1990 and 1994 and lower pneumoconiosis prevalence in 1999 relative to the G allele (0.33 versus 0.77 and 8.2 versus 19.6%, respectively). Smoking- or dust-adjustment, and stratification on IL18R1 genotype and adjustment for haplotype effects did not change the conclusions. In conclusion, the results of the present study suggest a role for IL18 in reducing the development of this fibrosing lung disease.

  4. [Effects of canine IL-2 and IL-7 genes on enhancing immunogenicity of canine parvovirus VP2 gene vaccine in mice].

    Science.gov (United States)

    Chen, Huihui; Zhong, Fei; Li, Xiujin; Wang, Lu; Sun, Yan; Neng, Changai; Zhang, Kao; Li, Wenyan; Wen, Jiexia

    2012-11-04

    To investigate the effects of canine interleukin-2 (cIL-2) and cIL-7 genes on enhancing the immunogenicity of canine parvovirus (CPV) VP2 DNA vaccine. The bicistronic vectors of cIL-2 and cIL-7 genes were constructed using the eukaryotic expression vector containing internal ribosome entry site (IRES). The cIL-2/ cIL-7 dicistronic vector plus previously constructed vectors, including CPV VP2 DNA vaccine vector, cIL-2 vector and cIL-7 vector, were used to co-immunize mice with different combinations, consisting of VP2 alone, VP2 + cIL-2, VP2 + cIL-7 and VP2 + cIL-2/cIL-7. The VP2-specific antibody levels in immunized mice were measured by ELISA at different time post-immunization. The proliferation indices and interferon-gamma expression were measured by lymphocyte proliferation assay and ELISA, respectively. The cIL-2/cIL-7 bicistronic vector was correct and could mediate cIL-2 and cIL-7 gene expression in eukaryotic cells. Immunization results revealed that the antibody titers and the neutralizing antibody levels of the mice co-immunized with VP2 + cIL-7/cIL-2 vectors were significantly higher than that with either VP2 + cIL-2 vectors or VP2 + cIL-7 vectors (P vaccine.

  5. Serum IL-6 level and associated factors: hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Seifi S, Mokhtari A

    2008-07-01

    Full Text Available "nBackground: The annual amount of mortality in ESRD exceeds the expectation and represents the recent evidences of the inflammation as its etiology. The etiology of inflammation is not clearly known. Chronic inflammation is a dominant occurrence of ESRD which increases the risk of atherosclerosis, malnutrition and peripheral vascular disease. Inflammatory responses are orchestrated by cytokines. Some of the proinflammatory cytokines like IL-6 have a crucial role in this phenomenon. The IL-6 and its receptor activity is up regulated in ESRD patients and the increased level of IL-6 predicts cardiovascular mortality and morbidity in normal and CRF patients. This study devotes itself to determining the serum level of IL-6 and factors affecting it in patients undergoing chronic hemodialysis in Imam Khomeini Hospital which can represent the Iranian Society. By identifying factors affecting the serum level of IL-6 and high-risk patients we can provide treatment possibilities, a decrease in mortality and an improvement in its prognosis. "n"nMethods: In this study 42 patients in Imam Dialysis Center were chosen and their serum IL-6 levels were measured at 2 times at three month interval and at the same time blood sample analysis were done for the following: Alb CPR, Ca, P, PTH, TIBC, Ferritin, TG, Chol, LDL, HDL, Uric Acid, Hb, WBC and urea."n"nResults: The mean serum level of IL-6 in hemodialysis patients was 6.35±4.47pg/ml (minimum: 0.55, maximum: 18.25 with the normal range of 1.3±3.2pg/ml."n"nConclusions: The IL-6 level was higher than normal range in the 52% of the patients. The serum IL-6 level had a significant correlations with CPR, Ferritin, TIBC, WBC and their serum IL-6 level was significantly higher in patients with hypertension, but no significant correlation was observed between other parameters and IL-6

  6. Clinical significance of determination of serum IL-1β, TNF-α levels in patients with periodontitis

    International Nuclear Information System (INIS)

    Wei Dong; Zhang Xiaolei

    2006-01-01

    Objective: To investigate the changes of serum IL-1β and TNF-α levels in patients with periodontitis. Methods: Serum IL-1β and TNF-α levels were measured with RIA in 42 patients with periodontitis and 35 controls. Results: Serum IL-1β and TNF-α levels in the patients were significantly higher than those in controls (P<0.01). Serum IL-1β level was positively correlated with TNF-α level (r=0.4182, P<0.01). Conclusion: Increase of serum IL-1β and TNF-α levels in patients with periodontitis was closely related to the pathogenesis of the disease. (authors)

  7. Configurational Reassignment and Improved Preparation of the Competitive IL-6 Receptor Antagonist 20R,21R-Epoxyresibufogenin-3-formate

    Science.gov (United States)

    Boos, Terrence L.; Cheng, Kejun; Greiner, Elisabeth; Deschamps, Jeffrey R.; Jacobson, Arthur E.; Rice, Kenner C.

    2012-01-01

    20R,21R-Epoxyresibufogenin-3-formate (1) and 20S,21S-epoxyresibufogenin-3-formate (2) were synthesized from commercial resibufogenin (3) using known procedures. The major product (1) was dextrorotatory, as was the major product from the reported synthesis of epoxyresibufogenin-3-formate; however, the literature (+)-compound was assigned the 20S,21S-configuration based on NMR data. We have now unequivocally determined, using single-crystal X-ray structure analyses of the major and minor products of the synthesis and of their derivatives, that the major product from the synthesis was (+)-20R,21R-epoxyresibufogenin-3-formate (1). Our minor synthetic product was determined to have the (-)-20S,21S-configuration (2). The (+)-20R,21R-compound 1 has been found to have high affinity for the IL-6 receptor and to act as an IL-6 antagonist. A greatly improved synthesis of 1 was achieved through oxidation of preformed resibufogenin-3-formate. This has enabled us to prepare, from the very expensive commercial resibufogenin, considerably larger quantities of 1, the only known non-peptide small molecule IL-6 antagonist. PMID:22360661

  8. Clinical significance of determination of changes of serum IL-6, IL-8, IL-10 and IL-18 levels after treatment in patients with chronic renal diseases

    International Nuclear Information System (INIS)

    Liu Congjiang; Li Fen; Zhang Lei; Liu Jianhua

    2008-01-01

    Objective: To explore the changes of serum IL-6, IL-8, IL-10 and IL-18 levels after treatment in patients with chronic renal diseases. Methods: Serum IL-6, IL-8, IL-10 levels were determined with RIA and IL-18 levels with ELISA in 32 patients with chronic renal diseases both before and after treatment as well as in 35 controls. Results: Before treatment the serum IL -6, IL-8, IL-10 and IL-18 levels were significantly higher in the patients than those in controls (P<0.01). After 6 months of treatment, the levels though dropped markedly remained significantly higher (P<0.05). Conclusion: Levels of serum IL-6, IL- 8, IL-10 and IL-18 increased significantly in patients with chronic renal diseases, especially in those advanced cases. (authors)

  9. Genetic regulation of IL1RL1 methylation and IL1RL1-a protein levels in asthma.

    Science.gov (United States)

    Dijk, F Nicole; Xu, Chengjian; Melén, Erik; Carsin, Anne-Elie; Kumar, Asish; Nolte, Ilja M; Gruzieva, Olena; Pershagen, Goran; Grotenboer, Neomi S; Savenije, Olga E M; Antó, Josep Maria; Lavi, Iris; Dobaño, Carlota; Bousquet, Jean; van der Vlies, Pieter; van der Valk, Ralf J P; de Jongste, Johan C; Nawijn, Martijn C; Guerra, Stefano; Postma, Dirkje S; Koppelman, Gerard H

    2018-03-01

    Interleukin-1 receptor-like 1 ( IL1RL1 ) is an important asthma gene. (Epi)genetic regulation of IL1RL1 protein expression has not been established. We assessed the association between IL1RL1 single nucleotide polymorphisms (SNPs), IL1RL1 methylation and serum IL1RL1-a protein levels, and aimed to identify causal pathways in asthma.Associations of IL1RL1 SNPs with asthma were determined in the Dutch Asthma Genome-wide Association Study cohort and three European birth cohorts, BAMSE (Children/Barn, Allergy, Milieu, Stockholm, an Epidemiological survey), INMA (Infancia y Medio Ambiente) and PIAMA (Prevention and Incidence of Asthma and Mite Allergy), participating in the Mechanisms of the Development of Allergy study. We performed blood DNA IL1RL1 methylation quantitative trait locus (QTL) analysis (n=496) and (epi)genome-wide protein QTL analysis on serum IL1RL1-a levels (n=1462). We investigated the association of IL1RL1 CpG methylation with asthma (n=632) and IL1RL1-a levels (n=548), with subsequent causal inference testing. Finally, we determined the association of IL1RL1-a levels with asthma and its clinical characteristics (n=1101). IL1RL1 asthma-risk SNPs strongly associated with IL1RL1 methylation (rs1420101; p=3.7×10 -16 ) and serum IL1RL1-a levels (p=2.8×10 -56 ). IL1RL1 methylation was not associated with asthma or IL1RL1-a levels. IL1RL1-a levels negatively correlated with blood eosinophil counts, whereas there was no association between IL1RL1-a levels and asthma.In conclusion, asthma-associated IL1RL1 SNPs strongly regulate IL1RL1 methylation and serum IL1RL1-a levels, yet neither these IL1RL1- methylation CpG sites nor IL1RL1-a levels are associated with asthma. Copyright ©ERS 2018.

  10. Decreased levels of soluble Toll-like Receptor 2 in patients with asthma

    Directory of Open Access Journals (Sweden)

    Mohsen Tehrani

    2012-10-01

    Full Text Available Background: Recently, reports have indicated a role for the membrane form of Toll-like Receptor 2 (TLR2 in asthma pathogenesis. In this study we examined soluble TLR2 levels in serum and sputum of asthmatic and healthy subjects. Methods: Serum and sputum samples were obtained from 33 asthmatic and 19 healthy subjects. The asthmatics were classified into four groups according to the Global Initiative for Asthma. A sandwich ELISA was developed to measure soluble TLR2 (sTLR2 in serum and sputum. TLR2 mRNA expression was determined by semi-quantitative RT-PCR of all sputum samples. Results: The mean sTLR2 levels from serum and sputum of asthmatics were significantly lower than those from healthy subjects. Moreover, sTLR2 concentration decreased concomitantly with asthma severity. The differences observed, however, were not statistically significant. TLR2/GAPDH mRNA of sputum leukocytes was also significantly lower in asthmatics than in healthy subjects. Conclusion: This study demonstrated for the first time thatsTLR2 levels are lower in serum and sputum samples from asthmatic than from healthy subjects, and this could be an indicator of TLR2 expression. We also found that sTLR2 concentration in serum decreased concomitantly with an increase of asthma severity clinical score.

  11. Identification of contact and respiratory sensitizers according to IL-4 receptor α expression and IL-2 production

    Energy Technology Data Exchange (ETDEWEB)

    Goutet, Michèle, E-mail: michele.goutet@inrs.fr; Pépin, Elsa; Langonné, Isabelle; Huguet, Nelly; Ban, Masarin

    2012-04-15

    Identification of allergenic chemicals is an important occupational safety issue. While several methods exist to identify contact sensitizers, there is currently no validated model to predict the potential of chemicals to act as respiratory sensitizers. Previously, we reported that cytometry analysis of the local immune responses induced in mice dermally exposed to the respiratory sensitizer trimellitic anhydride (TMA 10%) and contact sensitizer dinitrochlorobenzene (DNCB 1%) could identify divergent expression of several immune parameters. The present study confirms, first, that IgE-positive B cells, MHC class II molecules, interleukin (IL)-2, IL-4 and IL-4Rα can differentiate the allergic reactions caused by high doses of strong respiratory (TMA, phthalic anhydride and toluene diisocyanate) and contact sensitizers (DNCB, dinitrofluorobenzene and oxazolone). The second part of the study was designed to test the robustness of these markers when classing the weakly immunogenic chemicals most often encountered. Six respiratory allergens, including TMA (2.5%), five contact allergens, including DNCB (0.25%), and two irritants were compared at doses of equivalent immunogenicity. The results indicated that IL-4Rα and IL-2 can be reliably used to discriminate sensitizers. Respiratory sensitizers induced markedly higher IL-4Rα levels than contact allergens, while irritants had no effect on this parameter. Inversely, contact allergens tended to induce higher percentages of IL-2{sup +}CD8{sup +} cells than respiratory allergens. In contrast, the markers MHC-II, IgE and IL-4 were not able to classify chemicals with low immunogenic potential. In conclusion, IL-4Rα and IL-2 have the potential to be used in classifying a variety of chemical allergens. -- Highlights: ► Identification of chemical allergens is an important occupational safety issue. ► There is currently no model to predict the potential of chemicals to induce asthma. ► We analyze immune responses induced

  12. Identification of contact and respiratory sensitizers according to IL-4 receptor α expression and IL-2 production

    International Nuclear Information System (INIS)

    Goutet, Michèle; Pépin, Elsa; Langonné, Isabelle; Huguet, Nelly; Ban, Masarin

    2012-01-01

    Identification of allergenic chemicals is an important occupational safety issue. While several methods exist to identify contact sensitizers, there is currently no validated model to predict the potential of chemicals to act as respiratory sensitizers. Previously, we reported that cytometry analysis of the local immune responses induced in mice dermally exposed to the respiratory sensitizer trimellitic anhydride (TMA 10%) and contact sensitizer dinitrochlorobenzene (DNCB 1%) could identify divergent expression of several immune parameters. The present study confirms, first, that IgE-positive B cells, MHC class II molecules, interleukin (IL)-2, IL-4 and IL-4Rα can differentiate the allergic reactions caused by high doses of strong respiratory (TMA, phthalic anhydride and toluene diisocyanate) and contact sensitizers (DNCB, dinitrofluorobenzene and oxazolone). The second part of the study was designed to test the robustness of these markers when classing the weakly immunogenic chemicals most often encountered. Six respiratory allergens, including TMA (2.5%), five contact allergens, including DNCB (0.25%), and two irritants were compared at doses of equivalent immunogenicity. The results indicated that IL-4Rα and IL-2 can be reliably used to discriminate sensitizers. Respiratory sensitizers induced markedly higher IL-4Rα levels than contact allergens, while irritants had no effect on this parameter. Inversely, contact allergens tended to induce higher percentages of IL-2 + CD8 + cells than respiratory allergens. In contrast, the markers MHC-II, IgE and IL-4 were not able to classify chemicals with low immunogenic potential. In conclusion, IL-4Rα and IL-2 have the potential to be used in classifying a variety of chemical allergens. -- Highlights: ► Identification of chemical allergens is an important occupational safety issue. ► There is currently no model to predict the potential of chemicals to induce asthma. ► We analyze immune responses induced in mice

  13. IL-6 trans-signaling system in intra-amniotic inflammation, preterm birth, and preterm premature rupture of the membranes.

    Science.gov (United States)

    Lee, Sarah Y; Buhimschi, Irina A; Dulay, Antonette T; Ali, Unzila A; Zhao, Guomao; Abdel-Razeq, Sonya S; Bahtiyar, Mert O; Thung, Stephen F; Funai, Edmund F; Buhimschi, Catalin S

    2011-03-01

    Classic IL-6 signaling is conditioned by the transmembrane receptor (IL-6R) and homodimerization of gp130. During trans-signaling, IL-6 binds to soluble IL-6R (sIL-6R), enabling activation of cells expressing solely gp130. Soluble gp130 (sgp130) selectively inhibits IL-6 trans-signaling. To characterize amniotic fluid (AF) IL-6 trans-signaling molecules (IL-6, sIL-6R, sgp130) in normal gestations and pregnancies complicated by intra-amniotic inflammation (IAI), we studied 301 women during second trimester (n = 39), third trimester (n = 40), and preterm labor with intact (n = 131, 85 negative IAI and 46 positive IAI) or preterm premature rupture of membranes (PPROM; n = 91, 61 negative IAI and 30 positive IAI). ELISA, Western blotting, and real-time RT-PCR were used to investigate AF, placenta, and amniochorion for protein and mRNA expression of sIL-6R, sgp130, IL-6R, and gp130. Tissues were immunostained for IL-6R, gp130, CD15(+) (polymorphonuclear), and CD3(+) (T cell) inflammatory cells. The ability of sIL-6R and sgp130 to modulate basal and LPS-stimulated release of amniochorion matrix metalloprotease-9 was tested ex vivo. We showed that in physiologic gestations, AF sgp130 decreases toward term. AF IL-6 and sIL-6R were increased in IAI, whereas sgp130 was decreased in PPROM. Our results suggested that fetal membranes are the probable source of AF sIL-6R and sgp130. Immunohistochemistry and RT-PCR revealed increased IL-6R and decreased gp130 expression in amniochorion of women with IAI. Ex vivo, sIL-6R and LPS augmented amniochorion matrix metalloprotease-9 release, whereas sgp130 opposed this effect. We conclude that IL-6 trans-signaling molecules are physiologic constituents of the AF regulated by gestational age and inflammation. PPROM likely involves functional loss of sgp130.

  14. Multi-cellular natural killer (NK) cell clusters enhance NK cell activation through localizing IL-2 within the cluster

    Science.gov (United States)

    Kim, Miju; Kim, Tae-Jin; Kim, Hye Mi; Doh, Junsang; Lee, Kyung-Mi

    2017-01-01

    Multi-cellular cluster formation of natural killer (NK) cells occurs during in vivo priming and potentiates their activation to IL-2. However, the precise mechanism underlying this synergy within NK cell clusters remains unclear. We employed lymphocyte-laden microwell technologies to modulate contact-mediated multi-cellular interactions among activating NK cells and to quantitatively assess the molecular events occurring in multi-cellular clusters of NK cells. NK cells in social microwells, which allow cell-to-cell contact, exhibited significantly higher levels of IL-2 receptor (IL-2R) signaling compared with those in lonesome microwells, which prevent intercellular contact. Further, CD25, an IL-2R α chain, and lytic granules of NK cells in social microwells were polarized toward MTOC. Live cell imaging of lytic granules revealed their dynamic and prolonged polarization toward neighboring NK cells without degranulation. These results suggest that IL-2 bound on CD25 of one NK cells triggered IL-2 signaling of neighboring NK cells. These results were further corroborated by findings that CD25-KO NK cells exhibited lower proliferation than WT NK cells, and when mixed with WT NK cells, underwent significantly higher level of proliferation. These data highlights the existence of IL-2 trans-presentation between NK cells in the local microenvironment where the availability of IL-2 is limited.

  15. Association of IL1R polymorphism with HLA-B27 positive in Iranian patients with ankylosing spondylitis.

    Science.gov (United States)

    Mahmoudi, M; Amirzargar, A A; Jamshidi, A R; Farhadi, E; Noori, S; Avraee, M; Nazari, B; Nicknam, M H

    2011-12-01

    Ankylosing spondylitis (AS) is one of the most common causes of inflammatory arthritis, with an estimated prevalence of 0.1-0.9%. Genetic factors have been strongly implicated in its aetiology, and heritability as assessed by twin studies has been estimated to be >90%. HLA- B27 is almost essential for inheritance of AS; it is not merely sufficient for explaining the pattern of familial recurrence of the disease. This study's purpose is to investigate the association of ankylosing spondylitis with single-nucleotide polymorphisms (SNPs) in the IL-1 family: IL-1a (-889C/T) rs1800587, IL-1b (-511C/T) rs16944, IL-1b (+3962C/T) rs1143634, IL-1R (Pst-1 1970C/T) rs2234650 and IL-1RA (Mspa-1 11100C/T) rs315952. 99 unrelated Iranian AS patients and 217 healthy control subjects were selected. Cytokine typing was performed by the polymerase chain reaction with sequence-specific primers assay. The allele and genotype frequencies of the polymorphisms were determined: The IL1α rs1800587, IL1β rs16944 and IL1β rs1143634 were not significantly associated with AS. Genotype frequencies at IL1R rs2234650 differed between cases and controls (χ(2)=8.85; p=0.01); the IL1R rs2234650 C/T and T/T genotypes were less common in AS patients than controls. The IL1R rs2234650 C/T genotype was inversely associated with AS comparing with the IL1R rs2234650 C/C genotype (OR=0.48; p=0.005). IL1R rs2234650 C/T genotype was less common in patients than controls (OR=0.37; p=0.02).Furthermore IL1R rs2234650 T allele was strongly associated with HLA-B2702 patients rather than HLA-B2705 but was not associated with HLA-B27 negative patients (OR=0.33; p=0.01). Polymorphisms of IL1α rs1800587, IL1β rs16944 and IL1β rs1143634 were not significantly associated with ankylosing spondylitis but inversely in this study IL1R rs2234650 was significantly associated and carriage of T allele in IL1R rs2234650 seems to be protective, while carriage of C allele result in two fold higher risk of developing AS.

  16. Clinical significance of determination of some serum cytokines (IL-8, IL-10, IL-18, M-CSF) levels in patients with periodontitis

    International Nuclear Information System (INIS)

    Wei Dong; Zhang Xiaolei; Yang Chunxiu; Chen Guanghua

    2008-01-01

    Objective: To explore the significance of changes of serum IL-8, IL-10, IL-18 and M-CSF levels in patients with periodontitis. Methods: Serum levels of IL-8, IL-10, M-CSF (with RIA) and IL-18 (with ELISA) were measured in 55 patients with periodontitis both before and after treatment as well as in 35 controls. Results: Before treatment, serum levels of IL-8, IL-10, IL-18 and M-CSF were significantly higher in the patients than those in the controls (P<0.01). After one month of treatment, the serum IL-8, IL-10, IL-18 and M-CSF levels decreased somewhat, but were still significantly higher than those in controls (P<0.05). Conclusion: There was disturbance of immunomodulation in patients with periodontitis as expressed by the changes of several cytokines levels in the eourse of the diseases. (authors)

  17. Cytokines and Bone Loss in a 5-Year Longitudinal Study—Hormone Replacement Therapy Suppresses Serum Soluble Interleukin-6 Receptor and Increases Interleukin-1-Receptor Antagonist

    DEFF Research Database (Denmark)

    Abrahamsen, B.; Bonnevie-Nielsen, V.; Ebbesen, E.N.

    2000-01-01

    ) and the soluble IL-6 receptor (sIL-6R) potentially modify cytokine bioactivity. We therefore assessed the impact of menopause and hormone replacement therapy (HRT) on cytokines and activity modifiers in serum within a 5-year longitudinal study. One hundred sixty perimenopausal women (age 50.1 +/- 2.8 years) were.......16; p = 0.17). In conclusion, serum IL-1ra and sIL-6R are influenced by HRT and are associated with the rate of bone loss in perimenopausal women....

  18. IL-17A, IL-17RC polymorphisms and IL17 plasma levels in Tunisian patients with rheumatoid arthritis

    Science.gov (United States)

    Chahbi, Mayssa; Haouami, Youssra; Sfar, Imen; Abdelmoula, Leila; Ben Abdallah, Taieb; Gorgi, Yousr

    2018-01-01

    Background Interleukin-17 (IL-17), a cytokine mainly secreted by Th17 cells, seems to play a significant role in the pathogenesis of rheumatoid arthritis (RA). Functional genetic polymorphisms in IL-17 and its receptor genes can influence either qualitatively or quantitatively their functions. Therefore, we aimed to study the impact of IL17-A and IL17RC polymorphisms on plasma level of IL-17 and RA susceptibility and severity. Methods In this context, IL-17A*rs2275913 and IL-17RC*rs708567 polymorphisms were investigated together with the quantification of IL17 plasma level in 115 RA patients and 91 healthy control subjects matched in age, sex and ethnic origin. Results There were no statistically significant associations between IL-17A and IL-17RC studied polymorphisms and RA susceptibility. In contrast, IL-17A plasma levels were significantly higher in patients (55.07 pg/ml) comparatively to controls (4.75 pg/ml), p<10E-12. A ROC curve was used to evaluate the performance of plasma IL-17 in detecting RA. Given 100% specificity, the highest sensitivity of plasma IL-17A was 61.7% at a cut-off value of 18.25 pg/ml; p < 10E-21, CI = [0.849–0.939]. Analytic results showed that the IgM-rheumatoid factor and anti-CCP antibodies were significantly less frequent in patients with the IL-17RC*A/A genotype than those carrying *G/G and *G/A genotypes; p = 0.013 and p = 0.015, respectively. Otherwise, IL-17 plasma levels’ analysis showed a significant association with the activity of RA (DAS28≥5.1 = 74.71 pg/ml vs. DAS28<5.1 = 11.96 pg/ml), p<10E-6. Conclusion IL-17A*rs2275913 (G/A) and IL-17RC*rs708567 (G/A) polymorphisms did not seem to influence RA susceptibility in Tunisian population. This result agrees with those reported previously. Plasma IL-17A level seems to be predictive of severe RA occurrence. PMID:29584788

  19. Intravitreal injection of anti-Interleukin (IL)-6 antibody attenuates experimental autoimmune uveitis in mice.

    Science.gov (United States)

    Tode, Jan; Richert, Elisabeth; Koinzer, Stefan; Klettner, Alexa; Pickhinke, Ute; Garbers, Christoph; Rose-John, Stefan; Nölle, Bernhard; Roider, Johann

    2017-08-01

    To evaluate the effect of an intravitreally applied anti-IL-6 antibody for the treatment of experimental autoimmune uveitis (EAU). EAU was induced in female B10.RIII mice by Inter-Photoreceptor-Binding-Protein (IRBP) in complete Freund's adjuvant, boosted by Pertussis toxin. Single blinded intravitreal injections of anti-IL-6 antibody were applied 5-7days as well as 8-10days (3day interval) after EAU induction into the randomized treatment eye and phosphate buffered saline (PBS) into the fellow control eye. Clinical and fluorescein angiography scoring (6 EAU grades) was done at each injection day and at enucleation day 14. Enucleated eyes were either scored histologically (6 EAU grades) or examined by ELISA for levels of IL-6, IL-17 and IL-6 soluble Receptor (sIL-6R). Uveitis developed in all 12 mice. Clinical uveitis score was significantly reduced (p=0.035) in treated eyes (median 2.0, range 0-4.0, n=12) compared to the fellow control eyes (median 3.0, range 1.0-4.0, n=12). Angiography scores were reduced in 9/12 treated eyes and histological scores in 3/4 treated eyes compared to the fellow control eyes. Cytokine levels were determined in 8 mice, of which 4 responded to anti-IL-6 treatment and 4 did not respond. All mice responding to treatment had a significant reduction of IL-6 (ptreatment significantly attenuates experimental autoimmune uveitis in mice. EAU activity correlates with ocular IL-6 and IL-17 levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Association of NOD2 and IL23R with Inflammatory Bowel Disease in Puerto Rico

    Science.gov (United States)

    Ballester, Veroushka; Guo, Xiuqing; Vendrell, Roberto; Haritunians, Talin; Klomhaus, Alexandra M.; Li, Dalin; McGovern, Dermot P. B.; Rotter, Jerome I.; Torres, Esther A.; Taylor, Kent D.

    2014-01-01

    The Puerto Rico population may be modeled as an admixed population with contributions from three continents: Sub-Saharan Africa, Ancient America, and Europe. Extending the study of the genetics of inflammatory bowel disease (IBD) to an admixed population such as Puerto Rico has the potential to shed light on IBD genes identified in studies of European populations, find new genes contributing to IBD susceptibility, and provide basic information on IBD for the care of US patients of Puerto Rican and Latino descent. In order to study the association between immune-related genes and Crohn’s disease (CD) and ulcerative colitis (UC) in Puerto Rico, we genotyped 1159 Puerto Rican cases, controls, and family members with the ImmunoChip. We also genotyped 832 subjects from the Human Genome Diversity Panel to provide data for estimation of global and local continental ancestry. Association of SNPs was tested by logistic regression corrected for global continental descent and family structure. We observed the association between Crohn’s disease and NOD2 (rs17313265, 0.28 in CD, 0.19 in controls, OR 1.5, p = 9×10−6) and IL23R (rs11209026, 0.026 in CD, 0.0.071 in controls, OR 0.4, p = 3.8×10−4). The haplotype structure of both regions resembled that reported for European populations and “local” continental ancestry of the IL23R gene was almost entirely of European descent. We also observed suggestive evidence for the association of the BAZ1A promoter SNP with CD (rs1200332, 0.45 in CD, 0.35 in controls, OR 1.5, p = 2×10−6). Our estimate of continental ancestry surrounding this SNP suggested an origin in Ancient America for this putative susceptibility region. Our observations underscored the great difference between global continental ancestry and local continental ancestry at the level of the individual gene, particularly for immune-related loci. PMID:25259511

  1. Association of NOD2 and IL23R with inflammatory bowel disease in Puerto Rico.

    Directory of Open Access Journals (Sweden)

    Veroushka Ballester

    Full Text Available The Puerto Rico population may be modeled as an admixed population with contributions from three continents: Sub-Saharan Africa, Ancient America, and Europe. Extending the study of the genetics of inflammatory bowel disease (IBD to an admixed population such as Puerto Rico has the potential to shed light on IBD genes identified in studies of European populations, find new genes contributing to IBD susceptibility, and provide basic information on IBD for the care of US patients of Puerto Rican and Latino descent. In order to study the association between immune-related genes and Crohn's disease (CD and ulcerative colitis (UC in Puerto Rico, we genotyped 1159 Puerto Rican cases, controls, and family members with the ImmunoChip. We also genotyped 832 subjects from the Human Genome Diversity Panel to provide data for estimation of global and local continental ancestry. Association of SNPs was tested by logistic regression corrected for global continental descent and family structure. We observed the association between Crohn's disease and NOD2 (rs17313265, 0.28 in CD, 0.19 in controls, OR 1.5, p = 9×10-6 and IL23R (rs11209026, 0.026 in CD, 0.0.071 in controls, OR 0.4, p = 3.8×10-4. The haplotype structure of both regions resembled that reported for European populations and "local" continental ancestry of the IL23R gene was almost entirely of European descent. We also observed suggestive evidence for the association of the BAZ1A promoter SNP with CD (rs1200332, 0.45 in CD, 0.35 in controls, OR 1.5, p = 2×10-6. Our estimate of continental ancestry surrounding this SNP suggested an origin in Ancient America for this putative susceptibility region. Our observations underscored the great difference between global continental ancestry and local continental ancestry at the level of the individual gene, particularly for immune-related loci.

  2. IL-6 signaling in diabetic nephropathy: From pathophysiology to therapeutic perspectives.

    Science.gov (United States)

    Feigerlová, Eva; Battaglia-Hsu, Shyue-Fang

    2017-10-01

    Diabetic nephropathy (DN) is a leading cause of chronic kidney disease (CKD). Interleukin-6 (IL-6) signaling participates in inflammation responses central to the progression of DN. Current evidence suggests that these IL-6 responses are mediated via gp130-STAT3 dependent mechanisms which, on one hand, trigger globally the transition from innate to adaptive immune response, and on the other hand act locally for tissue remodeling and immune cell infiltration. In diabetic conditions the role of IL-6 is not well elucidated. Both IL-6 classical signaling pathway via receptor IL-6R (IL-6R) and IL-6 trans-signaling pathway via soluble IL-6R (sIL-6R) were shown to participate in the pathogenesis and progression of DN, and IL-6 appears to influence renal cells also in an autocrine manner. To date, evidence is limited. The goal of this review is to provide an overview of our current understanding on the role of IL-6 signaling in DN and to delineate challenges for future research. Putative sequential events related to IL-6 secretion by different cell populations in diabetic conditions are outlined. Further, we discuss potential applications of anti-IL-6 therapy in the context of DN. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Immunotherapy of human cancer with lak cells and IL-2

    International Nuclear Information System (INIS)

    Choi, Kyu Chul; Nam, Sang Yun; Ha, Youn Mun; Choi, Yong Mook

    1988-01-01

    The effects of adoptive immunotherapy with LAK cells and/or IL-2 were evaluated in 18 patients with advanced cancer for whom standard therapy had proved ineffective, from Jul. 1985 to Jan. 1988. Six patients were treated with LAK cells only, 4 patients treated with continuous IV infusion of IL-2 alone, and 8 patients treated with LAK cells plus IL-2. In a patient with hepatoma LAK cells and IL-2 were infused by selective catheterization to a branch of hepatic artery, in a patient with gastric cancer complicated by cancer peritonities LAK cells and IL-2 were infused to peritoneal cavity, and in a patient with renal cell carcinoma HLA-matched allogeneic LAK cells from 2 siblings were infused intravenously(8 times, total 2.49 X 10 10 cells). In the patient with gastric cancer who was treated by peritoneal infusion, LAK cells were induced from mononuclear cells obtained from ascites. Of 17 evaluable patients, 1(5.9%) had complete response(CR), 1(5.9%) had partial response (PR), 4(23.5%) had minimal responses(Min R), and 2(11.8%) had mixed responses(Mix R). Especially, of 7 evaluable patients treated with LAK cells plus IL-2, 1(14.3%) had CR, 1(14.3%) had PR, and 3(42.9%) had Min R. CR with relapse-free survival for 19 months was observed in a lung cancer (squamous cell carcinoma). PR was observed in a lung cancer, and Min R were observed in 2 hepatomas, 1 gastric cancer and 1 neuroblastoma. In 3 pediatric patients (3 to 7 years old) continuous infusion of IL-2 in dose-escalation mode were studied. They were able to tolerate 4,000,000 KH u/M 2 /day for 7 days of IL-2(1 KH u=1.1 BRMP u). Most of adult patients well tolerated 2,000,000 KH u/M 2 /day for 5 days of IL-2 in mode of continuous IV infusion. Most common side effects were chills and fever which could be prevented or minimized by premedication of antihistamine, indomethacin and acetaminophen, and IV infusion of demerol. Serious side effects were complicated by capillary leak syndrome which showed hypotension

  4. Profile of IL-2, IL-4, IL-10, IFN- ? , TNF- ? and KC-like cytokines in pregnant bitches

    Directory of Open Access Journals (Sweden)

    M.A.R. Feliciano

    2014-08-01

    Full Text Available The aim of this study was to determine the profile of IL-2, IL-4, IL-10, IFN-γ, and TNF-α cytokines and KC-like cells (natural killer in pregnant bitches, unpublished values for the species. A total of 27 females of the Shi Tzu, Pug, English Bulldog and French breeds, weighing 4-20kg and aged 4-6 years were used. Blood samples were collected from bitches during the anestrous and on the 2nd, 5th, 6th, 7th and 8th week of pregnancy. Serum levels of cytokines were measured by panel MILLIPLEX MAP (CCYTO-90K, MILLIPORE, Billerica, Massachusetts, USA validated for dogs. Twenty four females showed physiological pregnancy and three bitches showed pathological pregnancy. There was no difference between cytokine values during anestrous and gestational weeks of bitches (P>0.05. However, it was possible to verify the physiological behavior of serum levels during modulation of immune response in the gestational process of animals. In animals with gestational disorders, abnormal values for IL-2, IL-4 and INF-y were noted. It was concluded that serum levels of cytokines evaluated in pregnant bitches can help the better understanding of physiological and pathological gestational processes and correlated immunology in this species.

  5. IL-13 R130Q single nucleotide polymorphism in asthmatic Egyptian ...

    African Journals Online (AJOL)

    Background: Asthma and its associated phenotypes are under a substantial degree of genetic control. The common variant IL-13 gene polymorphism R130Q is reported to be associated with the risk of development of asthma in some populations. Objective: We sought to study the association of IL-13 genetic variant R130Q ...

  6. Imaging of inflamed carotid artery atherosclerotic plaques with the use of {sup 99m}Tc-HYNIC-IL-2 scintigraphy in end-stage renal disease patients

    Energy Technology Data Exchange (ETDEWEB)

    Opalinska, Marta; Pach, Dorota; Sowa-Staszczak, Anna; Glowa, Boguslaw; Hubalewska-Dydejczyk, Alicja [Jagiellonian University Medical School, Nuclear Medicine Unit, Department of Endocrinology, Cracow (Poland); Stompor, Tomasz [University of Warmia and Mazury in Olsztyn, Department of Nephrology, Hypertensiology and Internal Medicine, Faculty of Medicine, Olsztyn (Poland); Mikolajczak, Renata; Garnuszek, Piotr; Maurin, Michal; Karczmarczyk, Urszula [National Centre for Nuclear Research Radioisotope Centre POLATOM, Otwock (Poland); Fedak, Danuta [Jagiellonian University Medical School, Clinical Biochemistry, Cracow (Poland); Krzanowski, Marcin; Sulowicz, Wladyslaw [Jagiellonian University Medical School, Department of Nephrology, Cracow (Poland); Rakowski, Tomasz [Jagiellonian University Medical School, 2nd Department of Cardiology, Institute of Cardiology, Cracow (Poland)

    2012-04-15

    Identification of vulnerable plaques remains crucial for better cardiovascular risk assessment. At least 20% of inflammatory cells within unstable (vulnerable) plaques comprise T lymphocytes, which contain receptors for interleukin-2 (IL-2); those receptors can be identified by scintigraphy with radiolabelled IL-2.The aim of this study was to identify the ''inflamed'' (vulnerable) plaques by scintigraphy using IL-2 labelled with {sup 99m}Tc in the selected, high cardiovascular risk group of end-stage renal disease (ESRD) patients. A total of 28 patients (18 men, 10 women, aged 55.2 {+-} 9.6 years, 17 on peritoneal dialysis, 11 on haemodialysis) underwent common carotid artery (CCA) scintigraphy with the use of {sup 99m}Tc-hydrazinonicotinamide (HYNIC)-IL-2. In all cases, ultrasound examination of the CCA was performed and levels of selected proinflammatory factors, atherogenic markers and calcium-phosphate balance parameters were measured. Finally, the target to non-target (T/nT) ratio of IL-2 uptake in atherosclerotic plaques with intima-media thickness (IMT), classic cardiovascular risk factors and concentrations of the measured factors were compared. Increased {sup 99m}Tc-HYNIC-IL-2 uptake in atherosclerotic plaques in 38/41 (91%) cases was detected. The median T/nT ratio of focal {sup 99m}Tc-HYNIC-IL-2 uptake in atherosclerotic plaques was 2.35 (range 1.23-3.63). The mean IMT value on the side of plaques assessed by scintigraphy was 0.79 {+-} 0.18 mm (median 0.8, range 0.5-1.275). Correlations between T/nT ratio and homocysteine (R = 0.22, p = 0.037), apolipoprotein B (apoB) (R = 0.31, p = 0.008), apoB to apoA-I ratio (R = 0.29, p = 0.012) and triglyceride concentration (R = 0.26, p = 0.021) were detected. A lower T/nT ratio in patients with better parameters of nutritional status (haemoglobin, albumin, adiponectin) in comparison with patients with worse nutritional parameters (3.20 {+-} 0.5 vs 2.16 {+-} 0.68, p = 0.025) was revealed as well

  7. Clinical significance of measurement of changes of serum IL-6, IL-18 and IL-1β levels after treatment in patients with endometriosis

    International Nuclear Information System (INIS)

    Zhang Chunyan; Zhang Shumin; Zhou Dongxia; Wang Enbo

    2008-01-01

    Objective: To explore the clinical significance of changes of serum IL-6, IL-18 and IL-1β levels after treatment in patients with endometriosis. Methods: Serum IL-6 (with RIA) and IL-18, IL-1β (with ELISA) levels were determined in 38 patients with endometriosis both before and after treatment as well as 35 controls. Results: Before treatment, the serum IL-6, IL- 18 and IL-1β levels were significantly higher in the patients than those in controls (P 0.05). Conclusion: Detection of serum IL-6, IL-18 and IL- 1β levels might reflect the progress of diseases in patients with endometriosis. (authors)

  8. Changes of plasma IL-6 and TNF-α levels after CPAP treatment in patients with obstructive sleep apnea syndrome (OSAS)

    International Nuclear Information System (INIS)

    Cao Zhuo; Wang Liangxing

    2009-01-01

    Objective: To investigate the changes of plasma IL-6 and TNF-α levels after continuous positive airway pressure (CPAP) therapy in patients with obstructive sleep apnea syndrome (OSAS). Methods: Plasma IL-6 and TNF-α levels were measured with RIA in 60 patients with OSAS both before and after CPAS therapy as well as in 30 controls. Results: Before CPAP therapy, the plasma IL-6 and TNF-α levels in patients with OSAS were significantly higher than those in controls (25.92 ± 4.48pg/ ml and 11.27 ± 2.60pg/ml vs 13.21 ± 1.97pg/ml and 5.83±0.99pg/mi, P 2 level (r=-0.495, 0.483, P<0.05). After treatment with CPAP for three months, the plasma IL-6 and TNF-α levels were significantly decreased (15.37±1.78pg/ml and 6.79±0.87pg/ml, vs pre-treatment levels, P<0.05, P<0.01). Conclusion: CPAP therapy could effectively decrease the plasma IL-6 and TNF-α levels in patients with OSAS. (authors)

  9. Elevated levels of circulating IL-18BP and perturbed regulation of IL-18 in schizophrenia

    Directory of Open Access Journals (Sweden)

    Palladino Ilaria

    2012-08-01

    Full Text Available Abstract Background The pleiotropic pro-inflammatory cytokine Interleukin (IL-18 has been proposed to play a role in schizophrenia, since elevated circulating levels of its protein and altered frequencies of genetic variants in its molecular system are reported in schizophrenic patients. Methods We analyzed 77 patients with schizophrenia diagnosis (SCZ and 77 healthy control subjects (HC for serum concentration of both IL-18 and its natural inhibitor, the IL-18 binding protein (IL-18BP. Results We confirmed that serum levels of total IL-18 are significantly increased in SCZ, as compared to HC. However, due to a highly significant increase in levels of circulating IL-18BP in SCZ, as compared to HC, the levels of free, bioactive IL-18 are not significantly different between the two groups. In addition, the relationships between the levels of IL-18 and its inhibitor, as well as between the two molecules and age appear dissimilar for SCZ and HC. In particular, the elevated levels of IL-18BP, likely a consequence of the body’s attempt to counteract the early prominent inflammation which characterizes schizophrenia, are maintained in earlier and later stages of the disease. However, the IL-18BP elevation appears ineffective to balance the IL-18 system in younger SCZ patients, while in older patients the levels of circulating bioactive IL-18 are comparable to those of HC, if not lower. Conclusions In conclusion, these findings indicate that the IL-18 system is perturbed in schizophrenia, supporting the idea that this pro-inflammatory cytokine might be part of a pathway of genetic and environmental components for vulnerability to the disease.

  10. Association between genes encoding components of the IL-4/IL-4 receptor pathway and dermatitis in children.

    Science.gov (United States)

    Hussein, Yousri M; Shalaby, Sally M; Nassar, Amani; Alzahrani, Saad S; Alharbi, Ayman S; Nouh, Maha

    2014-07-25

    To determine whether IL-4, IL-4Rα and STAT6 polymorphisms are associated with susceptibility to dermatitis in Egyptian children. We genotyped three groups of children, consisting of 106 atopic dermatitis (AD) children, 95 non-AD children, and 100 of healthy controls, for IL-4 (-590 C/T), (-33 C/T), IL-4Rα (I50V), (Q576R) and STAT6 (2964 G/A), (2892 C/T) gene polymorphisms using PCR-RFLP assay. Total serum IgE and serum IL-4 levels were detected by ELISA. There was a non-significant association of IL-4 -590 C/T, -33 C/T polymorphisms in the children with non-AD or those with AD when compared with the controls. We identified a significant association between IL-4Rα I50V, Q576R polymorphisms and dermatitis susceptibility in AD (p=0.002, dermatitis was found. Patients who were carriers of IL4 -590C, IL-4Rα I50V G, STAT6 2964 A and STAT6 2892 T had an increased risk of AD [OR and 95% CI: 3.2 (2.5-4.2), p=0.005]. Furthermore, there was no relation between each polymorphism and serum IL-4 level (p>0.05 for each) while homozygosity for the risk alleles of IL-4, IL-4Rα and STAT6 SNPs were significantly associated with increased total IgE levels in all subjects. In Egyptian children, the IL-4Rα and the STAT6 polymorphism may play a role in susceptibility to AD. In addition, gene-gene interaction between the IL-4, the IL-4Rα and the STAT6 significantly increases an individual's susceptibility to AD. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Proinflammatory Soluble Interleukin-15 Receptor Alpha Is Increased in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Ana Cecilia Machado Diaz

    2012-01-01

    Full Text Available Rheumatoid arthritis (RA is an autoimmune and inflammatory disease in which many cytokines have been implicated. In particular, IL-15 is a cytokine involved in the inflammatory processes and bone loss. The aim of this study was to investigate the existence in synovial fluid of soluble IL-15Rα, a private receptor subunit for IL-15 which may act as an enhancer of IL-15-induced proinflammatory cytokines. Soluble IL-15Rα was quantified by a newly developed enzyme-linked immunosorbent assay (ELISA in samples of synovial fluid from patients with RA and osteoarthritis (OA. The levels of IL-15Rα were significantly increased in RA patients compared to OA patients. Also, we studied the presence of membrane-bound IL-15 in cells from synovial fluids, another element necessary to induce pro-inflammatory cytokines through reverse signaling. Interestingly, we found high levels of IL-6 related to high levels of IL-15Rα in RA but not in OA. Thus, our results evidenced presence of IL-15Rα in synovial fluids and suggested that its pro-inflammatory effect could be related to induction of IL-6.

  12. Increased IL-25 levels in the peritoneal fluid of patients with endometriosis.

    Science.gov (United States)

    Bungum, Helle Folge; Nygaard, Uffe; Vestergaard, Christian; Martensen, Pia M; Knudsen, Ulla Breth

    2016-04-01

    Previous studies have indicated a higher prevalence of allergic disease among women with endometriosis. It is already well established that type 1 allergies develop in a Th2 cytokine environment. Recent studies have shown, however, that IL-25 induces a Th2 development of naive T lymphocytes and is central in the Th2 response. The aim of this case-control study was to investigate the presence of IL-25 in the peritoneal fluid of women suffering from endometriosis. PF was obtained both from women undergoing laparoscopic surgery due to endometriosis (25 cases) and from women wanting sterilisation (19 controls). IL-25 levels were then investigated by ELISA. Women with endometriosis showed significantly higher levels of IL-25 in their PF (p=0.019) compared to controls. IL-25 levels did not correlate with the stage of endometriosis. Both Th2-cells and mast cells express IL-25, which could favor the development of allergies by perpetuating a hypersensitivity reaction. Further, IL-25 may also hold a role as a diagnostic tool. Copyright © 2016. Published by Elsevier Ireland Ltd.

  13. IL-1R and MyD88 signalling in CD4+ T cells promote Th17 immunity and atherosclerosis.

    Science.gov (United States)

    Engelbertsen, Daniel; Rattik, Sara; Wigren, Maria; Vallejo, Jenifer; Marinkovic, Goran; Schiopu, Alexandru; Björkbacka, Harry; Nilsson, Jan; Bengtsson, Eva

    2018-01-01

    The role of CD4+ T cells in atherosclerosis has been shown to be dependent on cytokine cues that regulate lineage commitment into mature T helper sub-sets. In this study, we tested the roles of IL-1R1 and MyD88 signalling in CD4+ T cells in atherosclerosis. We transferred apoe-/-myd88+/+ or apoe-/-myd88-/- CD4+ T cells to T- and B-cell-deficient rag1-/-apoe-/- mice fed high fat diet. Mice given apoe-/-myd88-/- CD4+ T cells exhibited reduced atherosclerosis compared with mice given apoe-/-myd88+/+ CD4+ T cells. CD4+ T cells from apoe-/-myd88-/- produced less IL-17 but similar levels of IFN-γ. Treatment of human CD4+ T cells with a MyD88 inhibitor inhibited IL-17 secretion in vitro. Transfer of il1r1-/- CD4+ T cells recapitulated the phenotype seen by transfer of myd88-/- CD4+ T cells with reduced lesion development and a reduction in Th17 and IL-17 production compared with wild type CD4+ T cell recipients. Relative collagen content of lesions was reduced in mice receiving il1r1-/- CD4+ T cells. We demonstrate that both IL1R and MyD88 signalling in CD4+ T cells promote Th17 immunity, plaque growth and may regulate plaque collagen levels. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.

  14. IL-6/IL-12 Cytokine Receptor Shuffling of Extra- and Intracellular Domains Reveals Canonical STAT Activation via Synthetic IL-35 and IL-39 Signaling.

    Science.gov (United States)

    Floss, D M; Schönberg, M; Franke, M; Horstmeier, F C; Engelowski, E; Schneider, A; Rosenfeldt, E M; Scheller, J

    2017-11-09

    IL-35 and IL-39 are recently discovered shared members of the IL-6- and IL-12-type cytokine family with immune-suppressive capacity. IL-35 has been reported to induce the formation of four different receptor complexes: gp130:IL-12β2, gp130:gp130, IL-12β2:IL-12β2, and IL-12β2:WSX-1. IL-39 was proposed to form a gp130:IL-23R receptor complex. IL-35, but not IL-39, has been reported to activate non-conventional STAT signaling, depending on the receptor complex and target cell. Analyses of IL-35 and IL-39 are, however, hampered by the lack of biologically active recombinant IL-35 and IL-39 proteins. Therefore, we engineered chimeric cytokine receptors to accomplish synthetic IL-35 and IL- 39 signaling by shuffling the extra- and intracellular domains of IL-6/IL-12-type cytokine receptors, resulting in biological activity for all previously described IL-35 receptor complexes. Moreover, we found that the proposed IL-39 receptor complex is biologically active and discovered two additional biologically active synthetic receptor combinations, gp130/IL-12Rβ1 and IL-23R/IL-12Rβ2. Surprisingly, synthetic IL-35 activation led to more canonical STAT signaling of all receptor complexes. In summary, our receptor shuffling approach highlights an interchangeable, modular domain structure among IL-6- and IL-12-type cytokine receptors and enabled synthetic IL-35 and IL-39 signaling.

  15. Clinical significance of measurement of changes of serum IL-2, TNF-α and IFN-γ levels after treatment in patients with psoriasis

    International Nuclear Information System (INIS)

    Mou Xudong; Ren Hong; Xie Chuntao

    2010-01-01

    Objective: To study the significance of changes of serum IL-2, TNF-α and IFN-γ levels after treatment in patients with psoriasis. Methods: Serum levels of IL-2, TNF-α (with RIA) and IFN-γ (with ELISA) were measured both before and after treatment in 37 patients with psoriasis and 35 controls. Results: Before treatment, the serum IL-2 levels in patients were significantly lower than those in controls (P<0.01), while the serum TNF-α and IFN-γ levels were significantly higher (P<0.01). After treatment for 3 months, the levels though markedly corrected, were still significantly different from those in controls (P<0.05). Conclusion: The levels of serum IL-2, TNF-α and IFN-γ increased significantly in patients with psoriasis especially in those advanced cases. (authors)

  16. An Epstein-Barr Virus MicroRNA Blocks Interleukin-1 (IL-1) Signaling by Targeting IL-1 Receptor 1.

    Science.gov (United States)

    Skinner, Camille M; Ivanov, Nikita S; Barr, Sarah A; Chen, Yan; Skalsky, Rebecca L

    2017-11-01

    Epstein-Barr virus (EBV) encodes >44 viral microRNAs (miRNAs) that are differentially expressed throughout infection, can be detected in Epstein-Barr virus (EBV)-positive tumors, and manipulate several biological processes, including cell proliferation, apoptosis, and immune responses. Here, we show that EBV BHRF1-2 miRNAs block NF-κB activation following treatment with proinflammatory cytokines, specifically interleukin-1β (IL-1β). Analysis of EBV PAR-CLIP miRNA targetome data sets combined with pathway analysis revealed multiple BHRF1-2 miRNA targets involved in interleukin signaling pathways. By further analyzing changes in cellular gene expression patterns, we identified the IL-1 receptor 1 (IL1R1) as a direct target of miR-BHRF1-2-5p. Targeting the IL1R1 3' untranslated region (UTR) by EBV miR-BHRF1-2-5p was confirmed using 3'-UTR luciferase reporter assays and Western blot assays. Manipulation of EBV BHRF1-2 miRNA activity in latently infected B cells altered steady-state cytokine levels and disrupted IL-1β responsiveness. These studies demonstrate functionally relevant BHRF1-2 miRNA interactions during EBV infection, which is an important step in understanding their roles in pathogenesis. IMPORTANCE IL-1 signaling plays an important role in inflammation and early activation of host innate immune responses following virus infection. Here, we demonstrate that a viral miRNA downregulates the IL-1 receptor 1 during EBV infection, which consequently alters the responsiveness of cells to IL-1 stimuli and changes the cytokine expression levels within infected cell populations. We postulate that this viral miRNA activity not only disrupts IL-1 autocrine and paracrine signaling loops that can alert effector cells to sites of infection but also provides a survival advantage by dampening excessive inflammation that may be detrimental to the infected cell. Copyright © 2017 American Society for Microbiology.

  17. Interleukin-2 and subunit alpha of its soluble receptor in autoimmune Addison's disease--an association study and expression analysis.

    Science.gov (United States)

    Fichna, Marta; Żurawek, Magdalena; Bratland, Eirik; Husebye, Eystein S; Kasperlik-Załuska, Anna; Czarnocka, Barbara; Januszkiewicz-Lewandowska, Danuta; Nowak, Jerzy

    2015-03-01

    Autoimmune Addison's disease (AAD) results from T cell-mediated destruction of the adrenal cortex, commonly accompanied by autoantibodies to 21-hydroxylase (21OH). In order to gain insight into the obscure aetiology of this disease, we investigated the roles of the IL2 and IL2RA genes, encoding interleukin-2 and subunit alpha of its receptor (IL2Ra), respectively. The association of AAD with IL2 and IL2RA polymorphisms (rs6822844, rs2069762, rs3136534, rs11594656, rs3118470 and rs2104286) was tested in 223 patients and 672 healthy controls. Functional studies consisted of gene expression analysis in cultured PBMCs exposed to 21OH and evaluation of serum interleukin by ELISA assays. The frequency of the minor C allele of rs3136534 was significantly decreased in AAD subjects compared to controls (OR 0.71; 95%CI 0.561-0.887; p = 0.003). Only AAD cells responded to 21OH with an elevated IL2 and IL2RA mRNA synthesis (p = 0.004 and p = 0.009 versus controls, respectively), paralleled by increased supernatant levels of both cytokines (p = 0.031 and p = 0.001 versus controls). IL2 mRNA level in 21OH-stimulated AAD PBMCs correlated negatively with age (p = 0.036) and positively with serum antibodies to 21OH (p = 0.006). Carriers of the rs2104286 AA genotype demonstrated higher IL2RA mRNA (p = 0.022) and soluble IL2Ra secretion (p = 0.029) upon 21OH stimulation. Serum interleukin-2 in AAD subjects was significantly higher compared to controls (4.61 ± 4.3 versus 1.71 ± 3.2 pg/mL, p < 0.001), whereas sIL2Ra levels remained similar in both groups (p = 0.885). In conclusion, the study reveals an association between AAD and IL2 locus. It confirms specific 21OH-directed reactivity of the peripheral AAD lymphocytes, which display increased synthesis of interleukin-2 and sIL2Ra.

  18. Regulation of IL-6 and IL-8 production by reciprocal cell-to-cell interactions between tumor cells and stromal fibroblasts through IL-1α in ameloblastoma

    International Nuclear Information System (INIS)

    Fuchigami, Takao; Kibe, Toshiro; Koyama, Hirofumi; Kishida, Shosei; Iijima, Mikio; Nishizawa, Yoshiaki; Hijioka, Hiroshi; Fujii, Tomomi; Ueda, Masahiro; Nakamura, Norifumi; Kiyono, Tohru; Kishida, Michiko

    2014-01-01

    Highlights: • We studied the interaction between tumor cells and fibroblasts in ameloblastoma. • AM-3 ameloblastoma cells secreted significantly high IL-1α levels. • IL-1α derived from AM-3 cells promoted IL-6 and IL-8 secretion of fibroblasts. • IL-6 and IL-8 activated the cellular motility and proliferation of AM-3 cells. - Abstract: Ameloblastoma is an odontogenic benign tumor that occurs in the jawbone, which invades bone and reoccurs locally. This tumor is treated by wide surgical excision and causes various problems, including changes in facial countenance and mastication disorders. Ameloblastomas have abundant tumor stroma, including fibroblasts and immune cells. Although cell-to-cell interactions are considered to be involved in the pathogenesis of many diseases, intercellular communications in ameloblastoma have not been fully investigated. In this study, we examined interactions between tumor cells and stromal fibroblasts via soluble factors in ameloblastoma. We used a human ameloblastoma cell line (AM-3 ameloblastoma cells), human fibroblasts (HFF-2 fibroblasts), and primary-cultured fibroblasts from human ameloblastoma tissues, and analyzed the effect of ameloblastoma-associated cell-to-cell communications on gene expression, cytokine secretion, cellular motility and proliferation. AM-3 ameloblastoma cells secreted higher levels of interleukin (IL)-1α than HFF-2 fibroblasts. Treatment with conditioned medium from AM-3 ameloblastoma cells upregulated gene expression and secretion of IL-6 and IL-8 of HFF-2 fibroblasts and primary-cultured fibroblast cells from ameloblastoma tissues. The AM3-stimulated production of IL-6 and IL-8 in fibroblasts was neutralized by pretreatment of AM-3 cells with anti-IL-1α antibody and IL-1 receptor antagonist. Reciprocally, cellular motility of AM-3 ameloblastoma cells was stimulated by HFF-2 fibroblasts in IL-6 and IL-8 dependent manner. In conclusion, ameloblastoma cells and stromal fibroblasts behave

  19. Regulation of IL-6 and IL-8 production by reciprocal cell-to-cell interactions between tumor cells and stromal fibroblasts through IL-1α in ameloblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Fuchigami, Takao [Department of Biochemistry and Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Kibe, Toshiro [Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Koyama, Hirofumi; Kishida, Shosei; Iijima, Mikio [Department of Biochemistry and Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Nishizawa, Yoshiaki [Kagoshima University Faculty of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Hijioka, Hiroshi; Fujii, Tomomi [Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Ueda, Masahiro [Natural Science Centre for Research and Education, Kagoshima University, 1-21-24 Koorimoto, Kagoshima 890-8580 (Japan); Nakamura, Norifumi [Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Kiyono, Tohru [Department of Virology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuouku, Tokyo 104-0045 (Japan); Kishida, Michiko, E-mail: kmichiko@m2.kufm.kagoshima-u.ac.jp [Department of Biochemistry and Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan)

    2014-09-05

    Highlights: • We studied the interaction between tumor cells and fibroblasts in ameloblastoma. • AM-3 ameloblastoma cells secreted significantly high IL-1α levels. • IL-1α derived from AM-3 cells promoted IL-6 and IL-8 secretion of fibroblasts. • IL-6 and IL-8 activated the cellular motility and proliferation of AM-3 cells. - Abstract: Ameloblastoma is an odontogenic benign tumor that occurs in the jawbone, which invades bone and reoccurs locally. This tumor is treated by wide surgical excision and causes various problems, including changes in facial countenance and mastication disorders. Ameloblastomas have abundant tumor stroma, including fibroblasts and immune cells. Although cell-to-cell interactions are considered to be involved in the pathogenesis of many diseases, intercellular communications in ameloblastoma have not been fully investigated. In this study, we examined interactions between tumor cells and stromal fibroblasts via soluble factors in ameloblastoma. We used a human ameloblastoma cell line (AM-3 ameloblastoma cells), human fibroblasts (HFF-2 fibroblasts), and primary-cultured fibroblasts from human ameloblastoma tissues, and analyzed the effect of ameloblastoma-associated cell-to-cell communications on gene expression, cytokine secretion, cellular motility and proliferation. AM-3 ameloblastoma cells secreted higher levels of interleukin (IL)-1α than HFF-2 fibroblasts. Treatment with conditioned medium from AM-3 ameloblastoma cells upregulated gene expression and secretion of IL-6 and IL-8 of HFF-2 fibroblasts and primary-cultured fibroblast cells from ameloblastoma tissues. The AM3-stimulated production of IL-6 and IL-8 in fibroblasts was neutralized by pretreatment of AM-3 cells with anti-IL-1α antibody and IL-1 receptor antagonist. Reciprocally, cellular motility of AM-3 ameloblastoma cells was stimulated by HFF-2 fibroblasts in IL-6 and IL-8 dependent manner. In conclusion, ameloblastoma cells and stromal fibroblasts behave

  20. Genotype-Specific Regulation of Oral Innate Immunity by T2R38 Taste Receptor

    Science.gov (United States)

    Gil, Sucheol; Coldwell, Susan; Drury, Jeanie L.; Arroyo, Fabiola; Phi, Tran; Saadat, Sanaz; Kwong, Danny; Chung, Whasun Oh

    2015-01-01

    The bitter taste receptor T2R38 has been shown to regulate mucosal innate immune responses in the upper airway epithelium. Furthermore, SNPs in T2R38 influence the sensitivity to 6-n-propylthiouracil (PROP) and are associated with caries risk/protection. However, no study has been reported on the role of T2R38 in the innate immune responses to oral bacteria. We hypothesize that T2R38 regulates oral innate immunity and that this regulation is genotype-specific. Primary gingival epithelial cells carrying three common genotypes, PAV/PAV (PROP super-taster), AVI/PAV (intermediate) and AVI/AVI (non-taster) were stimulated with cariogenic bacteria Streptococcus mutans, periodontal pathogen Porphyromonas gingivalis or non-pathogen Fusobacterium nucleatum. QRT-PCR analyzed T2R38 mRNA, and T2R38-specific siRNA and ELISA were utilized to evaluate induction of hBD-2 (antimicrobial peptide), IL-1α and IL-8 in various donor-lines. Experiments were set up in duplicate and repeated three times. T2R38 mRNA induction in response to S. mutans was highest in PAV/PAV (4.3-fold above the unstimulated controls; p<0.05), while lowest in AVI/AVI (1.2-fold). In PAV/PAV, hBD-2 secretion in response to S. mutans was decreased by 77% when T2R38 was silenced. IL-1α secretion was higher in PAV/PAV compared to AVI/PAV or AVI/AVI with S. mutans stimulation, but it was reduced by half when T2R38 was silenced (p<0.05). In response to P. gingivalis, AVI/AVI showed 4.4-fold increase (p<0.05) in T2R38 expression, whereas the levels in PAV/PAV and AVI/PAV remained close to that of the controls. Secretion levels of IL-1α and IL-8 decreased in AVI/AVI in response to P. gingivalis when T2R38 was silenced (p<0.05), while the changes were not significant in PAV/PAV. Our data suggest that the regulation of gingival innate immunity by T2R38 is genotype-dependent and that the ability to induce a high level of hBD-2 by PAV/PAV carriers may be a reason for protection against caries in this group. PMID

  1. Clinical significance of changes of plasma endothelin vasoactive factors (ET and NO) as well as serum related interleukin (IL-6 and IL-8) levels in patients with pregnancy induced hypertension (PIH)

    International Nuclear Information System (INIS)

    Chen Ying

    2009-01-01

    Objective: To investigate the clinical etiological significance of changes of plasma endothelin (ET) and nitric oxide (NO) as well as serum interleukin-6 (IL-6) and interleukin-8 (IL-8) levels in patients with pregnancy induced hypertension. Methods: Plasma ET (with RIA), NO (with biochemistry) and serum IL-6, IL-8 (with RIA) levels were measured in 32 pregnant women with PIH, 35 normal pregnant women without PIH and 35 non-pregnant women (as controls). Results: The plasma ET, NO level were significantly higher in normal pregnant women than those in the non-pregnant women controls, while serum levels of IL-6 and IL-8 levels were only slightly higher without significance (P>0.05). Before treatment, the blood ET, IL-6 and IL- 8 levels were significantly higher in patients with pregnancy induced hypertension than those in the control (P<0.01), while plasma levels of NO were significantly decreased (P<0.01), Two weeks after treatment, the plasma ET, NO and serum IL-6 and IL-8 levels were markedly corrected with no significantly differences from those in controls. The ET levels and serum IL-6, IL-8 levels were mutually positively correlated (r=0.6097, 0.7213, P<0.01). Conclusion: Determination of changes of plasma ET and NO, serum IL-6 and IL-8 levels in patients with pregnancy induced hypertension was helpful for outcome prediction. (authors)

  2. Study on the changes of serum TNF-α, IL-1β, IL-6 and IL-8 levels in patients with coronary cardiac heart diseases

    International Nuclear Information System (INIS)

    Lu Xiaozhuo; Yu Xian

    2003-01-01

    Objective: To study the role TNF-α, IL-1β, IL-6 and IL-8 played in the pathogenesis of coronary cardiac heart diseases. Methods: Serum levels of TNF-α, IL-1β, IL-6 and IL-8 levels were determined by chemiluminescence immunoassay in 32 patients with stable angina, 39 patients with acute myocardial infarction and 36 controls. Results: Serum TNF-α, IL-1β, IL-6 and IL-8 levels in all patients were higher than those in controls. Remarkably increased level were seen in acute myocardial infarction group. Difference between control and patient groups were: stable angina group TNF-α, p<0.05, IL-6, p<0.01 and IL-8, p<0.05; acute myocardial infarction group TNF-α, p<0.01, IL-1β, p<0.05, IL-6, p<0.001 and IL-8, p<0.001. Conclusion: There is close relationship between serum TNF-α, IL-1β, IL-6, IL-8 levels and development of coronary cardiac heart disease. They play an important role in the pathogenesis through mutual induction and synergistic actions

  3. Serum concentration of IL-6, IL-2, TNF-α, and IFNγ in Vitiligo patients

    Directory of Open Access Journals (Sweden)

    Suman Singh

    2012-01-01

    Full Text Available Background: Vitiligo is an acquired depigmenting disorder characterized by the loss of functional melanocytes from the epidermis. Although the etiology of vitiligo is unknown, over the last few years, substantial data from clinical research has greatly supported the ′Autoimmune theory′ and this is supported by the frequent association of vitiligo with disorders that have an autoimmune origin, including Hashimoto′s thyroiditis, Graves disease, type 1 insulin-dependent diabetes mellitus, and Addison′s disease. As cytokines are important mediators of immunity, there is evidence to suggest that they play a major role in the pathogenesis of autoimmune diseases. Aim: Keeping this in view we have assayed sera for cytokine IL-6, IL-2, Tumor necrosis factor (TNF-α, and IFNγ in 80 cases of vitiligo and compared it with healthy subjects, in order to find out whether they play a role in the pathogenesis of vitiligo or not. Materials and Methods: Serum IL-6, IL-2, TNF-α, and IFNγ were done by the indirect enzyme linked immunosorbent assay (ELISA. Results: The mean serum IL-6 and IL-2 levels in the patient group were significantly higher when compared with those of the normal controls. The mean serum IFNγ level in patients with vitiligo was significantly lower than that in the control group. There was no significant difference in the serum level of TNF-α between vitiligo and healthy controls. Conclusion : An increase in the production of proinflammatory cytokines such as IL-6 and IL-2 in vitiligo patients may play an important role in melanocytic cytotoxicity. Thus, we speculate that the cytokine production of epidermal microenvironment may be involved in vitiligo.

  4. Soluble Suppression of Tumorigenicity-2 Predicts Hospital Mortality in Burn Patients: An Observational Prospective Cohort Pilot Study.

    Science.gov (United States)

    Ruiz-Castilla, Mireia; Bosacoma, Pau; Dos Santos, Bruce; Baena, Jacinto; Guilabert, Patricia; Marin-Corral, Judith; Masclans, Joan R; Roca, Oriol; Barret, Juan P

    2018-04-10

    The IL33/ST2 pathway has been implicated in the pathogenesis of different inflammatory diseases. Our aim was to analyze whether plasma levels of biomarkers involved in the IL33/ST2 axis might help to predict mortality in burn patients. Single-center prospective observational cohort pilot study performed at the Burns Unit of the Plastic and Reconstructive Surgery Department of the Vall d'Hebron University Hospital (Barcelona). All patients aged ≥18 years old with second or third-degree burns requiring admission to the Burns Unit were considered for inclusion. Blood samples were taken to measure levels of interleukins (IL)6, IL8, IL33, and soluble suppression of tumorigenicity-2 (sST2) within 24 h of admission to the Burns Unit and at day 3. Results are expressed as medians and interquartile ranges or as frequencies and percentages. Sixty-nine patients (58 [84.1%] male, mean age 52 [35-63] years, total body surface area burned 21% [13%-30%], Abbreviated Burn Severity Index 6 [4-8]) were included. Thirteen (18.8%) finally died in the Burns Unit. Plasma levels of sST2 measured at day 3 after admission demonstrated the best prediction accuracy for survival (area under the ROC curve 0.85 [0.71-0.99]; P < 0.001). The best cutoff point for the AUROC index was estimated to be 2,561. In the Cox proportional hazards model, after adjusting for potential confounding, a plasma sST2 level2,561 measured at day 3 was significantly associated with mortality (HR 6.94 [1.73-27.74]; P = 0.006). Plasma sST2 at day 3 predicts hospital mortality in burn patients.

  5. [Plasma IL-18 levels are related to insulin and are modulated by IL-18 gene polymorphisms].

    Science.gov (United States)

    Martinez-Hervas, Sergio; Martínez-Barquero, Vanesa; Nuñez Savall, Ester; Lendínez, Verónica; Olivares, Laura; Benito, Esther; Real, Jose T; Chaves, F Javier; Ascaso, Juan F

    2015-01-01

    Atherosclerosis is an inflammatory chronic disease influenced by multiple factors. Different prospective studies have shown that plasmatic levels of inflammatory markers were related to atherosclerosis and cardiovascular disease. To evaluate whether plasmatic levels of interleukin 18 (IL-18) are modulated by SNPs (single nucleotide polymorphisms) of the IL 18 gene and its possible association with insulin levels and other cardiovascular risk factors. 746 individuals were studied for a period of two years by opportunistic selection in the metropolitan area of Valencia. Parameters of lipid and glucose metabolism were analyzed by standard methodology. IL-18 was measured by ELISA. Individuals with insulin resistance showed significant higher levels of IL-18. IL 18 was significantly correlated with insulin levels and other cardiovascular risk factors. The CC genotype of the rs1834481 SNP was significantly associated with lower levels of IL-18. However, the GG genotype of the rs7559479 was associated with significant higher levels of IL-18. IL-18 is associated with insulin resistance and other cardiovascular risk factors, being those levels genetically regulated. Copyright © 2015 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  6. Interleukin-6, interleukin-8, and soluble tumor necrosis factor receptor-I in the cord blood as predictors of chronic lung disease in premature infants.

    Science.gov (United States)

    An, Hiromi; Nishimaki, Shigeru; Ohyama, Makiko; Haruki, Atsushi; Naruto, Takuya; Kobayashi, Naoki; Sugai, Toshiyuki; Kobayashi, Yoshinori; Mori, Masaaki; Seki, Kazuo; Yokota, Shumpei

    2004-11-01

    In order to predict the late-development of chronic lung disease of prematurity (CLD), cytokines in the cord blood were assessed in this study. Eighteen premature infants with CLD were enrolled. Cord blood plasma levels of cytokines of these infants and 12 control infants without CLD were measured including interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, soluble TNF receptor-I, and soluble IL-6 receptor using a cytometric bead array and an enzyme-linked immunosorbent assay. The cord blood IL-6, IL-8, and sTNFR-I levels were significantly elevated in CLD infants compared with those in control (P < .05). IL-1beta, IL-2, IL-4, IL-10, and IFN-gamma were undetectable in both groups. CLD infants with maternal chorioamnionitis had higher IL-6 than those without chorioamnionitis (P < .01). In CLD infants, IL-6 was higher in the infants who required prolonged oxygen therapy (P < .05). Elevated inflammatory cytokines in the cord blood are associated with the progression to CLD.

  7. B cell activating factor is central to bleomycin- and IL-17-mediated experimental pulmonary fibrosis.

    Science.gov (United States)

    François, Antoine; Gombault, Aurélie; Villeret, Bérengère; Alsaleh, Ghada; Fanny, Manoussa; Gasse, Paméla; Adam, Sylvain Marchand; Crestani, Bruno; Sibilia, Jean; Schneider, Pascal; Bahram, Seiamak; Quesniaux, Valérie; Ryffel, Bernhard; Wachsmann, Dominique; Gottenberg, Jacques-Eric; Couillin, Isabelle

    2015-01-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive devastating, yet untreatable fibrotic disease of unknown origin. We investigated the contribution of the B-cell activating factor (BAFF), a TNF family member recently implicated in the regulation of pathogenic IL-17-producing cells in autoimmune diseases. The contribution of BAFF was assessed in a murine model of lung fibrosis induced by airway administered bleomycin. We show that murine BAFF levels were strongly increased in the bronchoalveolar space and lungs after bleomycin exposure. We identified Gr1(+) neutrophils as an important source of BAFF upon BLM-induced lung inflammation and fibrosis. Genetic ablation of BAFF or BAFF neutralization by a soluble receptor significantly attenuated pulmonary fibrosis and IL-1β levels. We further demonstrate that bleomycin-induced BAFF expression and lung fibrosis were IL-1β and IL-17A dependent. BAFF was required for rIL-17A-induced lung fibrosis and augmented IL-17A production by CD3(+) T cells from murine fibrotic lungs ex vivo. Finally we report elevated levels of BAFF in bronchoalveolar lavages from IPF patients. Our data therefore support a role for BAFF in the establishment of pulmonary fibrosis and a crosstalk between IL-1β, BAFF and IL-17A. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Clinical significance of changes of serum NSE, TNF-α and IL-6 levels in patients with hypoxic ischemic encephalopathy

    International Nuclear Information System (INIS)

    Zhang Yuhong; Zhang Yujuan; Zhou Xiujuan; Shan Huali

    2010-01-01

    Objective: To study the clinical significance of changes of serum NSE, TNF-α and IL-6 levels in neonates with hypoxic ischemic encephalopathy. Methods: Serum NSE (with ELISA) and TNF-α, IL-6 (with RIA) levels were measured in 30 neonates with hypoxic ischemic encephalopathy and 30 controls. Results: Serum NSE, TNF-α and IL-6 levels were significantly higher in neonates with hypoxic-ischemic encephalopathy than those in controls (P<0.01). Serum NSE levels were positively correlated with those of TNF-α, IL-6 (r=0.5812, 0.6014, P<0.01). Conclusion: Serum NSE, TNF-α and IL-6 levels were closely related to the diseases process of hypoxic-ischemic encephalopathy. (authors)

  9. Effects of balneotherapy on serum IL-1, PGE2 and LTB4 levels in fibromyalgia patients.

    Science.gov (United States)

    Ardiç, Füsum; Ozgen, Merih; Aybek, Hülya; Rota, Simin; Cubukçu, Duygu; Gökgöz, Ali

    2007-03-01

    The purpose of this study was to investigate the clinical effects of balneotherapy in the treatment of Fibromyalgia Syndrome (FMS) and to determine if balneotherapy influences serum levels of inflammation markers, IL-1, PGE2 and LTB4. 24 primary fibromyalgia female patients diagnosed according to American College of Rheumatology criteria were included to the study. Their ages ranged between 33 and 55 years. FMS patients were randomly assigned in two groups as, group 1 (n = 12) and group 2 (n = 12). Group 1 received 20-min bathing, once in a day for five days per week. Patients participated in the study for 3 weeks (total of 15 sessions) in Denizli. Group 2 did not receive balneotherapy. FMS patients were evaluated by tenderness measurements (tender point count and algometry), Visual Analogue Scale, Beck's Depression Index, Fibromyalgia Impact Questionnaire. Ten healthy women recruited group three as the controls. Serum PGE2, LTB4 and IL1-alpha levels were measured in all three groups. The biochemical measurements and clinical assessments were performed before and at the end of general period of therapy. Statistically significant alterations in algometric score, Visual Analogue score, Beck's Depression Index and PGE2 levels (P balneotherapy between group 1 and 2. Mean PGE2 level of FMS patients were higher compared to healthy control group (P balneotherapy IL-1 and LTB4 significantly decreased in group 1 (P balneotherapy is an effective choice of treatment in patients with FMS relieving the clinical symptoms, and possibly influencing the inflammatory mediators.

  10. Overexpression of IL-7R alpha provides a competitive advantage during early T-cell development.

    Science.gov (United States)

    Laouar, Yasmina; Crispe, I Nicholas; Flavell, Richard A

    2004-03-15

    Critical checkpoints controlling early thymic T-cell development and homeostasis are set by the proper signaling function of the interleukin 7 receptor (IL-7R) and the pre-T-cell antigen receptor. Although alpha beta T-cell development is observed in IL-7- and IL-7R alpha-deficient mice, the number of thymocytes is significantly reduced, implying a role for the IL-7R in controlling the size of the thymic T-cell compartment. Here, we report the overexpression of IL-7R alpha that occurs in the early T-cell compartment from AKR/J mice, animals that are highly susceptible to the spontaneous development of thymoma. Increased IL-7R alpha was revealed by surface staining, and increased IL-7R alpha mRNA was documented by using reverse transcriptase-polymerase chain reaction (RT-PCR). This resulted in increased survival of AKR/J early thymocytes, shown by the decreased frequency of TUNEL(+) (terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate [dUTP]-fluorescein nick end labeling) cells. In an in vivo thymocyte repopulation model, AKR/J thymocytes had a selective advantage over healthy thymocytes. This advantage occurred at early stages of T-cell development. Our findings support the model that overexpression of growth factor receptors can contribute to proliferation and malignancy.

  11. Homeostasis of peripheral CD4+ T cells: IL-2R alpha and IL-2 shape a population of regulatory cells that controls CD4+ T cell numbers

    NARCIS (Netherlands)

    Almeida, Afonso R. M.; Legrand, Nicolas; Papiernik, Martine; Freitas, António A.

    2002-01-01

    We show that the lymphoid hyperplasia observed in IL-2Ralpha- and IL-2-deficient mice is due to the lack of a population of regulatory cells essential for CD4 T cell homeostasis. In chimeras reconstituted with bone marrow cells from IL-2Ralpha-deficient donors, restitution of a population of

  12. Ovarian hyperstimulation syndrome is correlated with a reduction of soluble VEGF receptor protein level and a higher amount of VEGF-A.

    Science.gov (United States)

    Pietrowski, D; Szabo, L; Sator, M; Just, A; Egarter, C

    2012-01-01

    Ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening condition associated with increased vascular permeability. The vascular endothelial growth factor (VEGF) system and its receptors have been identified as the main angiogenic factors responsible for increased capillary permeability and are therefore discussed as crucial for the occurrence of OHSS. Recently, a number of soluble receptors for the VEGFs have been detected (sVEGF-Rs) and it has been shown that these sVEGF-Rs compete with the membrane-standing VEGF-R to bind VEGFs. We analyzed the serum levels of soluble VEGF-R1, -R2 and -R3 in 34 patients suffering from OHSS and in 34 controls without this disease. In a subgroup analysis, we correlated the severity of the OHSS with the detected amounts of VEGF-R1, -R2 and -R3. In addition, we determined the amount of total VEGF-A in the samples. All the three soluble VEGF receptors tended to be higher in the control group compared with that in the OHSS group but this difference only reached significance for sVEGF-R2 (mean ± SEM: 15.5 ± 0.6 versus 13.8 ± 0.5 ng/ml, respectively, P< 0.05). In the subgroup analysis, sVEGF-R2 levels decreased as the severity of OHSS increased (OHSS-I: 16.8 ± 1.9 ng/ml and OHSS-III: 12.7 ± 1.0 ng/ml, P< 0.05) Moreover, the serum levels of total VEGF-A were higher in the OHSS group than those in the controls (537.7 ± 38.9 versus 351 ± 53.4 pg/ml, respectively P< 0.05). We propose that VEGF-A plays a role in the occurrence of OHSS, that the amount of biologically available VEGF-A is modulated by sVEGF-Rs and that different combinations of VEGF-A and sVEGF-R levels might contribute to the severity of OHSS.

  13. Morphological and Functional Characterization of IL-12Rβ2 Chain on Intestinal Epithelial Cells: Implications for Local and Systemic Immunoregulation.

    Science.gov (United States)

    Regoli, Mari; Man, Angela; Gicheva, Nadhezda; Dumont, Antonio; Ivory, Kamal; Pacini, Alessandra; Morucci, Gabriele; Branca, Jacopo J V; Lucattelli, Monica; Santosuosso, Ugo; Narbad, Arjan; Gulisano, Massimo; Bertelli, Eugenio; Nicoletti, Claudio

    2018-01-01

    Interaction between intestinal epithelial cells (IECs) and the underlying immune systems is critical for maintaining intestinal immune homeostasis and mounting appropriate immune responses. We have previously showed that the T helper type 1 (T H 1) cytokine IL-12 plays a key role in the delicate immunological balance in the gut and the lack of appropriate levels of IL-12 had important consequences for health and disease, particularly with regard to food allergy. Here, we sought to understand the role of IL-12 in the regulation of lymphoepithelial cross talk and how this interaction affects immune responses locally and systemically. Using a combination of microscopy and flow cytometry techniques we observed that freshly isolated IECs expressed an incomplete, yet functional IL-12 receptor (IL-12R) formed solely by the IL-12Rβ2 chain that albeit the lack of the complementary IL-12β1 chain responded to ex vivo challenge with IL-12. Furthermore, the expression of IL-12Rβ2 on IECs is strategically located at the interface between epithelial and immune cells of the lamina propria and using in vitro coculture models and primary intestinal organoids we showed that immune-derived signals were required for the expression of IL-12Rβ2 on IECs. The biological relevance of the IEC-associated IL-12Rβ2 was assessed in vivo in a mouse model of food allergy characterized by allergy-associated diminished intestinal levels of IL-12 and in chimeric mice that lack the IL-12Rβ2 chain on IECs. These experimental models enabled us to show that the antiallergic properties of orally delivered recombinant Lactococcus lactis secreting bioactive IL-12 (rLc-IL12) were reduced in mice lacking the IL-12β2 chain on IECs. Finally, we observed that the oral delivery of IL-12 was accompanied by the downregulation of the production of the IEC-derived proallergic cytokine thymic stromal lymphopoietin (TSLP). However, further analysis of intestinal levels of TSLP in IL-12Rβ2 -/- mice suggested

  14. Cell type-specific roles of Jak3 in IL-2-induced proliferative signal transduction

    International Nuclear Information System (INIS)

    Fujii, Hodaka

    2007-01-01

    Binding of interleukin-2 (IL-2) to its specific receptor induces activation of two members of Jak family protein tyrosine kinases, Jak1 and Jak3. An IL-2 receptor (IL-2R)-reconstituted NIH 3T3 fibroblast cell line proliferates in response to IL-2 only when hematopoietic lineage-specific Jak3 is ectopically expressed. However, the mechanism of Jak3-dependent proliferation in the fibroblast cell line is not known. Here, I showed that Jak3 expression is dispensable for IL-2-induced activation of Jak1 and Stat proteins and expression of nuclear proto-oncogenes in the IL-2R-reconstituted fibroblast cell line. Jak3 expression markedly enhanced these IL-2-induced signaling events. In contrast, Jak3 expression was essential for induction of cyclin genes involved in the G1-S transition. These data suggest a critical role of Jak3 in IL-2 signaling in the fibroblast cell line and may provide further insight into the cell type-specific mechanism of cytokine signaling

  15. Recombinant Mycobacterium bovis BCG producing IL-18 reduces IL-5 production and bronchoalveolar eosinophilia induced by an allergic reaction.

    Science.gov (United States)

    Biet, F; Duez, C; Kremer, L; Marquillies, P; Amniai, L; Tonnel, A-B; Locht, C; Pestel, J

    2005-08-01

    Allergic reactions occur through the exacerbated induction of a Th2 cell type expression profile and can be prevented by agents favoring a Th1 profile. Bacillus Calmette-Guérin (BCG) is able to induce high IFN-gamma levels and has been shown to decrease experimentally induced allergy. The induction of IFN-gamma is mediated by interleukin (IL)-12 known to be secreted upon mycobacterial infections and can be enhanced by IL-18 acting in synergy with IL-12. We evaluated the ability of a recombinant BCG strain producing IL-18 (rBCG) to modify the Th2 type responses in a murine model of ovalbumin (OVA)-dependent allergic reaction. Mice were injected intraperitoneally or intranasally with OVA at days 0 and 15 and exposed to an OVA aerosol challenge at days 29, 30, 31 and 34. At days 0 and 15, two additional groups of mice received OVA together with 5 x 10(6) colony forming units of either rBCG or nonrecombinant BCG. A time-course analysis of OVA-specific immunoglobulin (Ig)E, IgG1 and IgG2a levels indicated no significant difference between the three groups of mice. However, following in vitro stimulation with OVA, lymph node cells from rBCG-treated mice produced less IL-5 and more IFN-gamma than those of mice injected with nonrecombinant BCG. In addition, 48 h after the last OVA challenge, a strong reduction of bronchoalveolar eosinophilia was found in the rBCG-injected mice compared to the nontreated or nonrecombinant BCG-treated groups. These results indicate that the production of IL-18 by rBCG may enhance the immunomodulatory properties of BCG that suppress pulmonary Th2 responses and, in particular, decrease airway eosinophilia.

  16. Studies on the relationship between plasma CRP and TNF-α, IL-1β levels in aged patients with acute coronary syndrome

    International Nuclear Information System (INIS)

    Luo Nanping; Wang Xiangang; Hu Chengjin; Wang Ruishan

    2002-01-01

    Objective: To investigate the relationship between plasma TNF-α, IL-1β and CRP levels in aged patients with coronary heart disease and to define the inflammation marker which might recognize and predict acute coronary syndrome. Methods: Radioimmunoassay was used to detect plasma levels of TNF-α, IL-1β and CRP. Results: Plasma levels of TNF-α and IL-β in patients with acute coronary syndrome (ACS) were significantly higher than those in controls (p<0.05; p<0.01) and stable coronary heart disease (SCHD) (p<0.05; p<0.01). Plasma CRP levels in patients with ACS (7.99 +- 11.9 ml/L) were also significantly higher than those in controls (0.99 +- 1.5 mg/L; p<0.01) and patients with SCHD (2.71 +- 5.45 mg/L; p<0.05). There was positive correlation between CRP level and TNF-α (r=0.0545; p<0.01) as well as IL-β (r=0.31, p<0.05). Conclusion: The abnormal expression of cytokines in aged patients with coronary heart disease was correlative to inflammation marker CRP, which suggested that the abnormal expression to the occurrence of acute coronary syndrome and might serve as a marker of unstable atherosclerosis plaque

  17. Clinical significance of determination of changes in serum hs-CRP, IL-6, IL-10, and IL-18 levels after treatment in patients with acute conjunctivitis

    International Nuclear Information System (INIS)

    Liu Jun

    2007-01-01

    Objective: To study the clinical significance of changes of serum hs-CRP, IL-6, IL-10 and IL-18 levels in patients with acute conjunctivitis after treatment. Methods: Serum IL-6, IL-10 (with RIA) hs-CRP (with Immuno-turbidity) and IL-18 (with ELISA) levels were measured in 38 patients with acute conjunctivitis both before and after treatment as well as in 35 controls. Results: The serum hs-CRP, IL-6, IL-10 and IL-18 levels in the patients before treatment were significantly higher than those in the controls (P 0.05). Conclusion: Measurement of the changes of serum hs-CRP, IL-6, IL-10 and IL-18 levels after treatment might be inportant for outcome prediction in patients with acute conjunctivitis. (authors)

  18. Restoration of lymphocyte proliferation and CTL generation by murine rIL-2 after treatment of allogeneic stimulator cells by ultraviolet B irradiation, heat, or paraformaldehyde

    International Nuclear Information System (INIS)

    Flye, M.W.; Yu, S.

    1991-01-01

    Following a 5-day mixed lymphocyte culture (MLC), C3H/HeJ (H-2k) splenocytes stimulated with DBA/2 (H-2d) gamma-irradiated splenocytes (2000 rads) are specifically cytotoxic in a 4-hr 51 Cr-release assay to P815 (H-2d) target cells (62 +/- 2% cytolysis) but not to third-party EL4 (H-2b). However, when the DBA/2 stimulator cells were treated with heat inactivation (45 degree C for 1 hr), fixed with 1% paraformaldehyde (15 min), or irradiated with ultraviolet-B light (10(4) J/M2), no cell proliferation or cytolytic activity developed in the MLCs. The levels of IL-1, IL-2, and IL-6 from the supernatants of MLC using stimulators undergoing either of the three treatments were markedly decreased compared with that from gamma-irradiated stimulators. Both cell proliferation and specific cytolysis were restored in a dose-dependent fashion by the addition of murine rIL-2 to the MLCs. If the stimulator cells were first activated with 5 micrograms/ml pokeweed mitogen or lipopolysaccharide for 2 days, the subsequent treatment with heat, paraformaldehyde, or UV-B did not significantly affect the development of cytolysis (54-70% cytolysis). Suppressor cells were not detected when cells from the nonresponsive MLCs (2.5 x 10(6) cells) were added to an MLC freshly prepared with gamma-irradiated stimulator cells, or were injected intraperitoneally (50 x 10(6) cells) into naive mice 2 days before recovery and in vitro sensitization of splenocytes. Therefore, modification of the stimulating alloantigen can prevent the release of cytokines that function as an essential second signal in the development of the proliferative response and subsequent cytolysis. The cytokine found to be essential for restoration of this response is IL-2

  19. The effects of IL-6 and its receptors on bone loss in postmenopausal women

    International Nuclear Information System (INIS)

    Huang Xin; Yang Weiwen; Zhang Xueguang

    2001-01-01

    Objective: To investigate the effects of IL-6 and its receptors on bone loss in healthy women, and to assess the pathogenesis of the postmenopausal osteoporosis in women. Methods: One hundred and thirty one healthy women aged 31-72 including 64 sexual maturity women aged 31-52 were enrolled in four groups and 67 postmenopausal women, the years of menopause from 1 month to 23 years, were also enrolled in four groups. The bone mass of the lumbar-spine and femur were measured using dual-energy X-rays absorptiometry; the serum E 2 , FSH, BGP by radioimmunoassay (RIA); the serum IL-6, sIL-6R, sgp 130 by ELISA; the serum AKP, calcium, phosphate by auto-biochemistry instrument. Results: The BMD of lumbar-spine and right femur decreased following increase of age and the duration of menopause. Significant positive correlation was observed between BMD and E 2 . The serum IL-6, sIL-6R, sgp 130 level was low, and stable before menopause. The level of IL-6, sIL-6R, sgp 130 increased with variation of age and the duration of menopause. Significant negative correlation was observed between IL-6, sIL-6R, sgp 130 and E 2 , BMD. Serum AKP and BGP level was higher in postmenopausal women than that in sexual maturity women. The serum calcium level increased significantly soon after menopausal, then decreased to the normal level. The serum phosphate level had no difference in these groups. Conclusion: The main cause of postmenopausal osteoporosis is the unbalance of the bone formation and resorption

  20. Clinical significance of determination of changes of serum IL-8, IL-1β and TNF-α levels after treatment in patients with chronic prostatitis

    International Nuclear Information System (INIS)

    Lv Yuhong; Zhang Zaigao; Li Jiacheng

    2009-01-01

    Objective: To study the significance of changes of serum IL-8, IL-1β and TNF-α levels after treatment in patients with chronic prostatitis. Methods: Serum TNF-α (with RIA). IL-8, IL-1β(with ELISA) levels were determined in 40 patients with chronic prostatitis both before and after treatment as well as 35 controls. Results: Before treatment, the serum IL-8, IL-1β and TNF-α levels in the patients were significantly higher than those in controls (P<0.01). After 2 weeks treatment, the IL-8 and IL-1β levels dropped markedly, but remained significantly higher than those in controls (P<0.05). However,the serum TNF-α levels dropped more and were not much different from those in controls (P<0.05). Conclusion: IL-8, IL-1β and TNF-α could take part in the pathogenesis in chronic prostatitis in various ways and determination of these levels clinically important. (authors)

  1. Increased serum concentrations of soluble ST2 predict mortality after burn injury.

    Science.gov (United States)

    Hacker, Stefan; Dieplinger, Benjamin; Werba, Gregor; Nickl, Stefanie; Roth, Georg A; Krenn, Claus G; Mueller, Thomas; Ankersmit, Hendrik J; Haider, Thomas

    2018-06-27

    Large burn injuries induce a systemic response in affected patients. Soluble ST2 (sST2) acts as a decoy receptor for interleukin-33 (IL-33) and has immunosuppressive effects. sST2 has been described previously as a prognostic serum marker. Our aim was to evaluate serum concentrations of sST2 and IL-33 after thermal injury and elucidate whether sST2 is associated with mortality in these patients. We included 32 burn patients (total body surface area [TBSA] >10%) admitted to our burn intensive care unit and compared them to eight healthy probands. Serum concentrations of sST2 and IL-33 were measured serially using an enzyme-linked immunosorbent assay (ELISA) technique. The mean TBSA was 32.5%±19.6%. Six patients (18.8%) died during the hospital stay. Serum analyses showed significantly increased concentrations of sST2 and reduced concentrations of IL-33 in burn patients compared to healthy controls. In our study cohort, higher serum concentrations of sST2 were a strong independent predictor of mortality. Burn injuries cause an increment of sST2 serum concentrations with a concomitant reduction of IL-33. Higher concentrations of sST2 are associated with increased in-hospital mortality in burn patients.

  2. Clinical significance of changes of serum IGF-II, IL-2 and SOD levels after treatment in pediatric patients with bronchial pneumonia

    International Nuclear Information System (INIS)

    Zhou Hong; Hu Yan; Wei Guoyu; Huang Jufeng

    2011-01-01

    Objective: To investigate the clinical significance of changes of serum IGF-II, IL-2 and SOD levels after treatment in pediatric patients with bronchial pneumonia. Methods: Serum IGF-II, IL-2 and SOD (with RIA) levels were measured in 33 pediatric patients with bronchial pneumonia both before and after treatment as well as in 35 controls. Results: Before treatment, serum IGF-II levels in the patients were significantly higher than those in controls (P 0.05). Conclusion: Changes of serum IGF-II, IL-2 and SOD levels both before and after treatment could reflect the diseases status of the patients as well as the progress of diseases, and might be of prognostic importance in pediatric patients with bronchial pneumonia. (authors)

  3. Autoimmune manifestations in SCID due to IL7R mutations: Omenn syndrome and cytopenias.

    Science.gov (United States)

    Zago, Claudia Augusta; Jacob, Cristina Miuki Abe; de Albuquerque Diniz, Edna Maria; Lovisolo, Silvana Maria; Zerbini, Maria Claudia Nogueira; Dorna, Mayra; Watanabe, Letícia; Fernandes, Juliana Folloni; Rocha, Vanderson; Oliveira, João Bosco; Carneiro-Sampaio, Magda

    2014-07-01

    B+NK+SCID (severe combined immunodeficiency) due to IL7Rα deficiency represents approximately 10% of American SCID cases. To better understand the spectrum of autoimmune disorders associated with IL7Rα deficiency, we describe two unrelated IL7Rα-deficient female SCID infants whose clinical picture was dominated by autoimmune manifestations: one with intrauterine Omenn syndrome (OS) and another with persistent thrombocytopenic purpura since 4months of age. The OS baby harbored a homozygous p.C118Y mutation in IL7R. She presented dense eosinophilic infiltrates in several organs, including pancarditis, which may have contributed to her death (on the 2nd day of life). B cells were observed in lymph nodes, spleen, bone marrow and thymus. The second patient harbored compound heterozygous p.C118Y and p.I121NfsX8 mutations. She underwent a successful unrelated cord blood transplant. In conclusion, early OS can be observed in patients with IL7R mutations, and autoimmune cytopenias could also complicate the clinical course of SCID babies with this type of defect. Copyright © 2014. Published by Elsevier Inc.

  4. Dynamic monitoring of serum IFN-γ, IL-2, and IL-6 contents in patients with Graves' disease

    International Nuclear Information System (INIS)

    Zou Jianwen; Li Weiguo

    2006-01-01

    Objective: To investigate the possible role of cytokines (IFN-γ, IL-2, IL-6) in the pathogenesis of Graves' disease. Methods: Serum FT 3 , FT 4 , TSH (with CLIA), IL-2, IL-6 (with RIA) and IFN-γ (with ELISA) contents were measured in the following subjects: (1) 42 patients with Graves' disease before any treatment, (2) 40 patients in remission after successful treatment with antithyroid drugs (ATD), (3) 25 patients in relapse (around 6 months after cessation of two years' ATD treatment, (4) 40 controls. Results: The serum IFN-γ and IL-6 contents in the patients before treatment and patients in relapse were significantly higher than those in the controls (P 3 , FT 4 levels while the serum IL-2 contents were linearly negatively correlated with FT 3 , FT 4 levels before treatment. Conclusion: Contents of these cytokines fluctuated dynamically along with the status of Graves' disease and might be related to the pathogenesis in some way. (authors)

  5. IL-1β level in Sudanese patients with atherosclerotic coronary heart ...

    African Journals Online (AJOL)

    McRoy

    studies investigating inflammatory cytokines in atherosclerotic patients with coronary heart disease (CHD).[2,5-7]. However, systemic level of IL-1β may still be unreliable marker for atherosclerosis. This is because systemic level of IL-1β could not faithfully reflect the local inflammatory process near the atheromatous lesions.

  6. Immunoadjuvant activities of a recombinant chicken IL-12 in chickens vaccinated with Newcastle disease virus recombinant HN protein.

    Science.gov (United States)

    Su, Bor Sheu; Yin, Hsien Sheng; Chiu, Hua Hsien; Hung, Li Hsiang; Huang, Ji Ping; Shien, Jui Hung; Lee, Long Huw

    2011-08-05

    Recombinant fowlpox virus (rFPV/HN) expressing Newcastle disease virus (NDV) HN gene and rFPV/HN/chIL-12 co-expressing chicken IL-12 (chIL-12) and HN (rHN/chIL-12) genes have been characterized. rHN/chIL-12 or rchIL-12, expressed by our previous construct rFPV/chIL-12, co-administered with rHN was assessed for adjuvant activities of chIL-12. Chickens were vaccinated with various amounts of rHN/chIL-12 mixed with mineral oil (MO), intramuscularly. Levels of hemagglutination-inhibition (HI) antibody production depended on the concentration of the injected rHN or rHN/chIL-12. The lower HI antibody titers were obtained in chicken groups rHN/chIL-12/7-rHN/chIL-12/9, receiving 60ng rHN/8ng chIL-12 with MO, 30ng rHN/4ng chIL-12 with MO or 15ng rHN/2ng chIL-12 with MO, respectively, compared to those in chicken groups rHN/7-rHN/9, receiving rHN with MO alone. However, chickens in group rHN/chIL-12/7 or rHN/chIL-12/8 and rHN with MO alone showed the same effective protection. Chicken group rHN/chIL-12/9 was even more protective than that in group rHN/9. When rchIL-12 was co-injected with 15ng rHN plus MO, chickens produced low levels of HI antibody titers; while higher levels of IFN-γ production and an effective protection rate (83%) were obtained. On the other hand, low levels of IFN-γ production and low protection response (50%) were obtained in chickens injected with rHN with MO alone. Taken together, when the concentration of rHN decreased to certain levels, rchIL-12 reduced HI antibody production. The increase in the induction of IFN-γ production might suggest the enhancement of the cell-mediated immunity which conferred the protection from the NDV challenge. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Influence of different thyroid functional statuses on human serum IL-8, TNF levels

    International Nuclear Information System (INIS)

    Wei Feng; Jiao Yanxiang; Guang Yancen; Zhang Zhu; Wei Cuiying

    2003-01-01

    Objective: To evaluate the effect of different statuses of thyroid function (hyperthyroidism and hypothyroidism as well as euthyroid status) on serum IL-8, TNF levels. Methods: Serum IL-8, TNF levels of 95 hyperthyroidism patients (41 males, 54 females), 53 hypothyroidism patients (23 males, 30 females), 45 euthyroid controls (24 males, 21 females) were measured with RIA. Results: 1. Serum IL-8 levels in hyperthyroidism (Graves' disease) patients were significantly higher than those in controls. (F=2.93, p 0.05). IL-8 and TNF levels were also not correlated to age and thyroid hormone levels. Conclusion: Both IL-8 and TNF took part in many auto-immure pathological processes including hyper-and hypo-thyroidism

  8. α-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8.

    LENUS (Irish Health Repository)

    Bergin, David A

    2010-12-01

    Hereditary deficiency of the protein α-1 antitrypsin (AAT) causes a chronic lung disease in humans that is characterized by excessive mobilization of neutrophils into the lung. However, the reason for the increased neutrophil burden has not been fully elucidated. In this study we have demonstrated using human neutrophils that serum AAT coordinates both CXCR1- and soluble immune complex (sIC) receptor-mediated chemotaxis by divergent pathways. We demonstrated that glycosylated AAT can bind to IL-8 (a ligand for CXCR1) and that AAT-IL-8 complex formation prevented IL-8 interaction with CXCR1. Second, AAT modulated neutrophil chemotaxis in response to sIC by controlling membrane expression of the glycosylphosphatidylinositol-anchored (GPI-anchored) Fc receptor FcγRIIIb. This process was mediated through inhibition of ADAM-17 enzymatic activity. Neutrophils isolated from clinically stable AAT-deficient patients were characterized by low membrane expression of FcγRIIIb and increased chemotaxis in response to IL-8 and sIC. Treatment of AAT-deficient individuals with AAT augmentation therapy resulted in increased AAT binding to IL-8, increased AAT binding to the neutrophil membrane, decreased FcγRIIIb release from the neutrophil membrane, and normalization of chemotaxis. These results provide new insight into the mechanism underlying the effect of AAT augmentation therapy in the pulmonary disease associated with AAT deficiency.

  9. Study on IL-2 and CA 15-3 level as combined biomarkers in monitoring chemotherapeutic response among invasive breast cancer patients

    Science.gov (United States)

    Hameed, Ahmed Muthanna Abdul; Hamid, Auni Fatin Abdul; Shahfiza Noor, Nurul; Appalanaido, Gokula Kumar; Bariyah Sahul Hamid, Shahrul

    2017-05-01

    In Malaysia, breast cancer is the most frequent type of disease among women. This study was designed to determine the clinical usefulness of carbohydrate antigen (CA 15-3) and interleukin 2 (IL-2) levels as combined biomarkers in monitoring breast cancer patient’s response to chemotherapy. Ethical approval was obtained to recruit patients with histologically confirmed invasive ductal carcinoma (IDC) attending Oncology Clinic at Advanced Medical and Dental Institute. Whole blood was collected from 10 IDC breast cancer patients’ pre and post primary chemotherapy. Plasma was separated from the whole blood to determine the CA 15-3 level and IL-2 level using enzyme-linked immunosorbent assay (ELISA) pre and post-treatment. In addition, the histological findings, tumour stage and other patients’ data were obtained from the medical record. Findings showed that IL-2 had borderline significant changes between pre- and post-chemotherapy (p = 0.074) whereas for CA 15-3, there was insignificant differences of CA 15-3 level between pre and post-chemotherapy (p > 0.05). It was noted that only CA 15-3 level had significant correlation with tumour size. This study demonstrates that IL-2 level requires further investigation in a larger sample size to correlate its potential use as combined biomarker with CA 15-3 in monitoring response to chemotherapy.

  10. A density functional theory insight towards the rational design of ionic liquids for SO2 capture.

    Science.gov (United States)

    García, Gregorio; Atilhan, Mert; Aparicio, Santiago

    2015-05-28

    A systematic density functional theory (DFT) analysis has been carried out to obtain information at the molecular level on the key parameters related to efficient SO2 capture by ionic liquids (ILs). A set of 55 ILs, for which high gas solubility is expected, has been selected. SO2 solubility of ILs was firstly predicted based on the COSMO-RS (Conductor-like Screening Model for Real Solvents) method, which provides a good prediction of gas solubility data in ILs without prior experimental knowledge of the compounds' features. Then, interactions between SO2 and ILs were deeply analyzed through DFT simulations. This work provides valuable information about required factors at the molecular level to provide high SO2 solubility in ILs, which is crucial for further implementation of these materials in the future. In our opinion, systematic research on ILs for SO2 capture increases our knowledge about those factors which could be controlled at the molecular level, providing an approach for the rational design of task-specific ILs.

  11. IL-4 Up-Regulates MiR-21 and the MiRNAs Hosted in the CLCN5 Gene in Chronic Lymphocytic Leukemia.

    Directory of Open Access Journals (Sweden)

    Natalia Ruiz-Lafuente

    Full Text Available Interleukin 4 (IL-4 induces B-cell differentiation and survival of chronic lymphocytic leukemia (CLL cells. MicroRNAs (miRNAs regulate mRNA and protein expression, and several miRNAs, deregulated in CLL, might play roles as oncogenes or tumor suppressors. We have studied the miRNA profile of CLL, and its response to IL-4, by oligonucleotide microarrays, resulting in the detection of a set of 129 mature miRNAs consistently expressed in CLL, which included 41 differentially expressed compared to normal B cells (NBC, and 6 significantly underexpressed in ZAP-70 positive patients. IL-4 stimulation brought about up-regulation of the 5p and 3p mature variants of the miR-21 gene, which maps immediately downstream to the VMP1 gene, and of the mature forms generated from the miR-362 (3p and 5p, miR-500a (3p, miR-502 (3p, and miR-532 (3p and 5p genes, which map within the third intron of the CLCN5 gene. Both genes are in turn regulated by IL-4, suggesting that these miRNAs were regulated by IL-4 as passengers from their carrier genes. Their levels of up-regulation by IL-4 significantly correlated with cytoprotection. MiR-21 has been reported to be leukemogenic, associated to bad prognosis in CLL, and the miRNA more frequently overexpressed in human cancer. Up-regulation by IL-4 of miR-21 and the miRNAs hosted in the CLCN5 locus may contribute to evasion of apoptosis of CLL cells. These findings indicate that the IL-4 pathway and the miRNAs induced by IL-4 are promising targets for the development of novel therapies in CLL.

  12. Clinical significance of measurement of serum NO, IL-6 and IL-8 levels after treatment in patients with schizophrenia

    International Nuclear Information System (INIS)

    Gao Wanqin

    2010-01-01

    Objective: To study the significance of changes of serum NO, IL-6 and IL-8 levels after treatment in patients with schizophrenia. Methods: Serum IL-6, IL-8 (with RIA) and NO (with bio-chemistry) levels were determined in 37 patients with schizophrenia both before and after treatment as well as in 35 controls. Results: Before treatment, the serum IL-6, IL-8 levels in the patients were significantly higher than those in controls (P<0.01). While the serum NO levels were significantly lower (P<0.01). After six weeks' treatment, the levels of IL-6, IL-8 in the patients, though dropped markedly still remained significantly higher (P<0.05) than those in controls. The serum NO levels, though markedly increased after treatment, were still remained significantly lower than those in the controls (P<0.05). Conclusion: Serum NO, IL-6 and IL-8 levels were closely related to the diseases process of schizophrenia and were of prognostic values. (authors)

  13. IL-21 Receptor Expression in Human Tendinopathy

    Directory of Open Access Journals (Sweden)

    Abigail L. Campbell

    2014-01-01

    Full Text Available The pathogenetic mechanisms underlying tendinopathy remain unclear, with much debate as to whether inflammation or degradation has the prominent role. Increasing evidence points toward an early inflammatory infiltrate and associated inflammatory cytokine production in human and animal models of tendon disease. The IL-21/IL-21R axis is a proinflammatory cytokine complex that has been associated with chronic inflammatory diseases including rheumatoid arthritis and inflammatory bowel disease. This project aimed to investigate the role and expression of the cytokine/receptor pair IL-21/IL-21R in human tendinopathy. We found significantly elevated expression of IL-21 receptor message and protein in human tendon samples but found no convincing evidence of the presence of IL-21 at message or protein level. The level of expression of IL-21R message/protein in human tenocytes was significantly upregulated by proinflammatory cytokines (TNFα/IL-1β in vitro. These findings demonstrate that IL-21R is present in early human tendinopathy mainly expressed by tenocytes and macrophages. Despite a lack of IL-21 expression, these data again suggest that early tendinopathy has an inflammatory/cytokine phenotype, which may provide novel translational targets in the treatment of tendinopathy.

  14. IL-33 circulating serum levels are increased in patients with non-segmental generalized vitiligo.

    Science.gov (United States)

    Vaccaro, Mario; Cicero, Francesca; Mannucci, Carmen; Calapai, Gioacchino; Spatari, Giovanna; Barbuzza, Olga; Cannavò, Serafinella P; Gangemi, Sebastiano

    2016-09-01

    IL-33 is a recently identified cytokine, encoded by the IL-33 gene, which is a member of the IL-1 family that drives the production of T-helper-2 (Th-2)-associated cytokines. Serum levels of IL-33 have been reported to be up-regulated in various T-helper (Th)-1/Th-17-mediated diseases, such as psoriasis, rheumatoid arthritis, and inflammatory bowel. To investigate whether cytokine imbalance plays a role in the pathogenesis of vitiligo, we performed a case-control association study by enzyme-linked immunosorbent assay of IL-33 in our patients. IL-33 serum levels were measured by a quantitative enzyme immunoassay technique in patients with non-segmental generalized vitiligo and compared with those of healthy controls. IL-33 serum levels in patients with vitiligo were significantly increased than those in healthy controls. There was a positive correlation of IL-33 serum levels with extension of vitiligo and disease activity. This study suggests a possible systemic role of IL-33 in the pathogenesis of vitiligo. Inhibiting IL-33 activity might be a novel therapeutic strategy in the treatment of autoimmune inflammatory disease, like vitiligo.

  15. Cell type-specific roles of Jak3 in IL-2-induced proliferative signal transduction

    Science.gov (United States)

    Fujii, Hodaka

    2007-01-01

    Binding of IL-2 to its specific receptor induces activation of two members of Jak family protein tyrosine kinases, Jak1 and Jak3. An IL-2R-reconstituted NIH 3T3 fibroblast cell line proliferates in response to IL-2 only when hematopoietic lineage-specific Jak3 is ectopically expressed. However, the mechanism of Jak3-dependent proliferation in the fibroblast cell line is not known. Here, I showed that Jak3 expression is dispensable for IL-2-induced activation of Jak1 and Stat proteins and expression of nuclear proto-oncogenes in the IL-2R-reconstituted fibroblast cell line. However, Jak3 expression markedly enhanced these IL-2-induced signaling events. In contrast, Jak3 expression was essential for induction of cyclin genes involved in the G1-S transition. These data suggest a critical role of Jak3 in IL-2 signaling in the fibroblast cell line and may provide further insight into the cell type-specific mechanism of cytokine signaling. PMID:17266928

  16. Concentraciones séricas de interleucina 2 y su receptor soluble, antes y después de una cirugía Serum concentrations of interleukin 2 and its soluble receptor, before and after surgery

    Directory of Open Access Journals (Sweden)

    Maczy González Rincón

    2006-12-01

    Full Text Available Con el objetivo de determinar las concentraciones séricas de interleucina 2 (IL-2 y su receptor soluble (RsIL-2 antes y después de una cirugía y su relación en cada período de estudio, se determinó, mediante inmunoensayo enzimático, los niveles de IL-2 y RsIL-2 antes y 24 horas después de la cirugía en 40 pacientes sometidos a cirugía menor y cirugía mayor. En cirugía menor se obtuvieron niveles promedio para IL-2 de 0,938 y 0,139 U/mL, para RsIL-2 de 364,8 y 497 pg/mL; mientras que en cirugía mayor los valores fueron: para IL-2 de 2,03 y 0,114 U/mL y RsIL-2 de 319,7 y 600 pg/mL, en cada período respectivamente. La disminución observada de los niveles de IL-2 y el incremento del RsIL-2 en cirugía mayor y menor podría sugerir una alteración de la respuesta inmunitaria celular, generada no sólo por el estrés quirúrgico, sino posiblemente por el efecto reconocido de los anestésicos en la depresión de la función óptima del sistema inmunitario

  17. Genetic characterization of interleukins (IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12A, IL-12B, IL-15 and IL-18) with relevant biological roles in lagomorphs

    Science.gov (United States)

    Neves, Fabiana; Abrantes, Joana; Almeida, Tereza; de Matos, Ana Lemos; Costa, Paulo P

    2015-01-01

    ILs, as essential innate immune modulators, are involved in an array of biological processes. In the European rabbit (Oryctolagus cuniculus) IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12A, IL-12B, IL-15 and IL-18 have been implicated in inflammatory processes and in the immune response against rabbit hemorrhagic disease virus and myxoma virus infections. In this study we characterized these ILs in six Lagomorpha species (European rabbit, pygmy rabbit, two cottontail rabbit species, European brown hare and American pika). Overall, these ILs are conserved between lagomorphs, including in their exon/intron structure. Most differences were observed between leporids and American pika. Indeed, when comparing both, some relevant differences were observed in American pika, such as the location of the stop codon in IL-1α and IL-2, the existence of a different transcript in IL8 and the number of cysteine residues in IL-1β. Changes at N-glycosylation motifs were also detected in IL-1, IL-10, IL-12B and IL-15. IL-1α is the protein that presents the highest evolutionary distances, which is in contrast to IL-12A where the distances between lagomorphs are the lowest. For all these ILs, sequences of human and European rabbit are more closely related than between human and mouse or European rabbit and mouse. PMID:26395994

  18. Serum IL-10, IL-17 and IL-23 levels as "bioumoral bridges" between dyslipidemia and atopy.

    Science.gov (United States)

    Manti, S; Leonardi, S; Panasiti, I; Arrigo, T; Salpietro, C; Cuppari, C

    2017-11-01

    Although several studies suggest a possible link between dyslipidemia and atopy, literature findings are still unclear. The aim of the study was to investigate the relationship between dyslipidemia and atopy in a pediatric population affected by dyslipidemia or dyslipidemia/atopic predisposition. Children with dyslipidemia, dyslipidemia and atopy as well as healthy children were recruited. Serum total IgE, IL-10, IL-17, and IL-23 levels as well as fasting lipid values (total cholesterol, LDL, HDL and triglycerides) were performed on all enrolled children. The present study evaluated 23 patients affected by dyslipidemia, 26 patients affected by atopy and dyslipidemia and, 22healthy children. Serum total IgE levels significantly related also with serum cholesterol levels: positively with total cholesterol (pdyslipidemia than patients with dyslipidemia (pdyslipidemia than patients with dyslipidemia (pdyslipidemia and atopic predisposition share the same immune pathways as well as they offer new insights in the complex crosstalk between hyperlipidemia and atopy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Salivary Levels of IL-6 and IL-17 Could Be an Indicator of Disease Severity in Patients with Calculus Associated Chronic Periodontitis

    Directory of Open Access Journals (Sweden)

    Husniah Batool

    2018-01-01

    Full Text Available Background/Purpose. Chronic periodontitis is an inflammatory disease of gums that causes loss of supporting structures of teeth, that is, gingiva, periodontal ligament, cementum, and alveolar bone. Levels of various cytokines in the serum, gingival tissues, and gingival crevicular fluid in patients with chronic periodontitis have been studied, but limited data are available on the level of cytokines in saliva. Therefore, a study was designed to determine levels of salivary IL-6 and IL-17 in patients with calculus associated chronic periodontitis. Materials and Methods. It was a comparative, cross-sectional study that is comprised of 41 healthy controls and 41 calculus associated chronic periodontitis patients (CP patients. According to the degree of attachment loss, CP patients were subcategorized as mild (CAL 1-2 mm, moderate (CAL 3-4 mm, and severe (CAL > 5 mm forms of periodontitis. Salivary levels of IL-6 and IL-17 were determined using enzyme-linked immunosorbent assay (ELISA technique. Data was analyzed using SPSS 20.0. Results. Between healthy controls and CP patients (moderate and severe disease, a statistically significant difference was observed in the concentrations of IL-6 and IL-17. In CP patients, the highest mean ± SD of salivary IL-6 and IL-17 was observed in severe CP, followed by moderate and mild CP. Regarding level of IL-6, a statistically significant difference was observed between mild and severe disease and between moderate and severe subcategories of CP patients. Similarly, statistically significant difference was observed in the level of IL-17 between mild and moderate, mild and severe disease, and moderate and severe disease. Conclusion. The levels of salivary IL-6 and IL-17 were increased significantly in calculus associated CP patients as compared to healthy controls and these levels increased with the progression of CP. Clinical Significance. Salivary levels of IL-6 and IL-17 may help in the subcategorization

  20. Radioimmunotoxicological effect of enriched uranium on central and peripheral immune cells and the protective action of IL-1 and IL-2

    International Nuclear Information System (INIS)

    Zhu Shoupeng; Lai Guanhua; Wang Liuyi

    1993-01-01

    With accumulation of enriched uranium 235 U-UO 2 F 2 in organism, it was found that enriched uranium had injurious effect on the immune function of central and peripheral immune cells. After intravenous injection of enriched uranium the spontaneous 3 H-TdR incorporation in thymocytes and bone marrow cells decreased. Though the sensitivity of immune cells to 235 U-UO 2 F 2 was different, the thymocytes were destroyed more markedly. Also the proliferation ability of T and B lymphocytes were both inhibited by enriched uranium 235 U. As compared with them, spleen B lymphocytes were inhibited more markedly than T lymphocytes. At the same time spleen lymphocytes IL-1 production and IL 2 consumption were diminished. It should be noted that the inhibition of spleen B lymphocytes proliferation by enriched uranium 235 U-UO 2 F 2 was partially restored by exogenous IL-1 or IL-2. The recovery rate of protective action at the very most was 67.1 +- 11.2% with exogenous IL-1 and 50.2 +- 8.0% with IL-2. Moreover, both exogenous IL-1 and IL-2 had synergetic effect, and the recovery rate was elevated to 83.1 +-12.3%

  1. Estrogen and progesterone decrease let-7f microRNA expression and increase IL-23/IL-23 receptor signaling and IL-17A production in patients with severe asthma.

    Science.gov (United States)

    Newcomb, Dawn C; Cephus, Jacqueline Yvonne; Boswell, Madison G; Fahrenholz, John M; Langley, Emily W; Feldman, Amy S; Zhou, Weisong; Dulek, Daniel E; Goleniewska, Kasia; Woodward, Kimberly B; Sevin, Carla M; Hamilton, Robert G; Kolls, Jay K; Peebles, R Stokes

    2015-10-01

    Women have an increased prevalence of severe asthma compared with men. IL-17A is associated with severe asthma and requires IL-23 receptor (IL-23R) signaling, which is negatively regulated by let-7f microRNA. We sought to Determine the mechanism by which 17β-estradiol (E2) and progesterone (P4) increase IL-17A production. IL-17A production was determined by using flow cytometry in TH17 cells from women (n = 14) and men (n = 15) with severe asthma. Cytokine levels were measured by using ELISA, and IL-23R and let-7f expression was measured by using quantitative PCR in TH17-differentiated cells from healthy women (n = 13) and men (n = 14). In sham-operated or ovariectomized female mice, 17β-E2, P4, 17β-E2+P4, or vehicle pellets were administered for 3 weeks before ex vivo TH17 cell differentiation. Airway neutrophil infiltration and CXCL1 (KC) expression were also determined in ovalbumin (OVA)-challenged wild-type female recipient mice with an adoptive transfer of OVA-specific TH17 cells from female and male mice. In patients with severe asthma and healthy control subjects, IL-17A production was increased in TH17 cells from women compared with men. IL-23R expression was increased and let-7f expression was decreased in TH17-differentiated cells from women compared with men. In ovariectomized mice IL-17A and IL-23R expression was increased and Let-7f expression was decreased in TH17 cells from mice administered 17β-E2+P4 compared with those administered vehicle. Furthermore, transfer of female OVA-specific TH17 cells increased acute neutrophil infiltration in the lungs of OVA-challenged recipient mice compared with transfer of male OVA-specific TH17 cells. 17β-E2+P4 increased IL-17A production from TH17 cells, providing a potential mechanism for the increased prevalence of severe asthma in women compared with men. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  2. Solubility of carbon dioxide in the ionic liquid 1-ethyl-3-methylimidazolium tris(pentafluoroethyl)trifluorophosphate

    NARCIS (Netherlands)

    Althuluth, M.A.M.; Mota Martinez, M.T.; Kroon, M.C.; Peters, C.J.

    2012-01-01

    Recently, the use of ionic liquids (ILs) for gas separation processes has attracted much attention because of the high solubility of different gaseous species in ILs. This contribution presents new experimental measurements of the carbon dioxide (CO2) solubility in the IL 1-ethyl-3 methylimidazolium

  3. Role of IL-1 beta and COX2 in silica-induced IL-6 release and loss of pneumocytes in co-cultures.

    Science.gov (United States)

    Herseth, Jan I; Refsnes, Magne; Låg, Marit; Schwarze, Per E

    2009-10-01

    The pro-inflammatory cytokines IL-1 beta, TNF-alpha and IL-6 are of great importance in the development of silica-induced lung damage and repair. In this study we investigated the role of IL-1 beta, TNF-alpha and COX2 in silica-induced regulation of IL-6 release and pneumocyte loss in various mono- and co-cultures of monocytes, pneumocytes and endothelial cells. All co-cultures with monocytes, and especially cultures including endothelial cells, showed an increase of silica-induced release of IL-6 compared to the respective monocultures. Treatment with the antagonist IL-1 ra strongly decreased IL-1 beta and IL-6 release in contact co-cultures of monocytes and pneumocytes. COX2 up-regulation by silica and IL-1 beta was eliminated by IL-1 ra. Inhibition of COX2 markedly reduced both IL-1 beta and IL-6 release. IL-1 ra was more effective than COX2-inhibition in reduction of IL-6, but not of IL-1 beta. Silica-induced pneumocyte loss was reduced by IL-1 beta, but this effect was not counteracted by the IL-1 receptor antagonist. Our findings suggest that silica-induced IL-6 release from pneumocytes is mainly mediated via IL-1 beta release from the monocytes, via both COX2-dependent and -independent pathways. Notably, COX2-derived mediators seem crucial for a positive feed-back regulation of IL-1 beta release from the monocytes. In contrast to silica-induced IL-6, the reduction in pneumocyte loss by IL-1 beta does not seem to be regulated through an IL-1R1-dependent mechanism.

  4. High levels of neutralizing IL-6 autoantibodies in 0.1% of apparently healthy blood donors

    DEFF Research Database (Denmark)

    Galle, Pia; Svenson, Morten; Bendtzen, Klaus

    2004-01-01

    deficiency. Here, we examined aAb-IL-6 in 4,230 blood donors. Stable low titers of aAb-IL-6 were found in 9% of the donors, while 1% had titers ranging from 64 to greater than 10,000. Such aAb-IL-6-positive donors appeared normal with no overt signs of pathology. Natural and recombinant forms of IL-6 bound...... avidly to their IgG, and their plasma strongly neutralized IL-6 in vitro. Slightly elevated concentrations of IL-6 exclusively in the form of IL-6-IgG complexes were present in their circulation. The complexes did not contain soluble IL-6 receptors. Titers of 0.1% of the blood donors were as positive...... as the vaccination-induced IL-6-deficient mice. Such donors might be IL-6 deficient, and if so, IL-6 seems be dispensable for several months in otherwise healthy individuals. Such highly positive donors also explain why normal human IgG for pharmaceutical use may contain high anti-IL-6 activity. Finally, transfusion...

  5. Gene expression profiling of the Notch-AhR-IL22 axis at homeostasis and in response to tissue injury.

    Science.gov (United States)

    Weidenbusch, Marc; Rodler, Severin; Song, Shangqing; Romoli, Simone; Marschner, Julian A; Kraft, Franziska; Holderied, Alexander; Kumar, Santosh; Mulay, Shrikant R; Honarpisheh, Mohsen; Kumar Devarapu, Satish; Lech, Maciej; Anders, Hans-Joachim

    2017-12-22

    Notch and interleukin-22 (IL-22) signaling are known to regulate tissue homeostasis and respond to injury in humans and mice, and the induction of endogenous aryl hydrocarbon receptor (Ahr) ligands through Notch links the two pathways in a hierarchical fashion. However in adults, the species-, organ- and injury-specific gene expression of the Notch-AhR-IL22 axis components is unknown. We therefore performed gene expression profiling of DLL1, DLL3, DLL4, DLK1, DLK2, JAG1, JAG2, Notch1, Notch2, Notch3, Notch4, ADAM17/TNF-α ADAM metalloprotease converting enzyme (TACE), PSEN1, basigin (BSG)/CD147, RBP-J, HES1, HES5, HEY1, HEYL, AHR, ARNT, ARNT2, CYP1A1, CYP24A1, IL-22, IL22RA1, IL22RA2, IL10RB, and STAT3 under homeostatic conditions in ten mature murine and human organs. Additionally, the expression of these genes was assessed in murine models of acute sterile inflammation and progressive fibrosis. We show that there are organ-specific gene expression profiles of the Notch-AhR-IL22 axis in humans and mice. Although there is an overall interspecies congruency, specific differences between human and murine expression signatures do exist. In murine tissues with AHR/ARNT expression CYP1A1 and IL-22 were correlated with HES5 and HEYL expression, while in human tissues no such correlation was found. Notch and AhR signaling are involved in renal inflammation and fibrosis with specific gene expression changes in each model. Despite the presence of all Notch pathway molecules in the kidney and a model-specific induction of Notch ligands, IL-22 was only up-regulated in acute inflammation, but rapidly down-regulated during regeneration. This implies that for targeting injury responses, e.g. via IL-22, species-specific differences, injury type and time points have to be considered. © 2017 The Author(s).

  6. Plasma cytokines in acute stroke

    DEFF Research Database (Denmark)

    Christensen, Hanne Krarup; Boysen, Gudrun; Christensen, Erik

    2011-01-01

    GOALS: The aim of this study was to test the relations between plasma cytokines and the clinical characteristics, course, and risk factors in acute stroke. PATIENTS AND METHODS: The analysis was based on 179 patients with acute stroke included within 24 hours of stroke onset. On inclusion and 3...... months later plasma levels of interleukin 1 beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), interleukin-1 receptor antagonist (IL-1RA), interleukin 6 (IL-6), interleukin 10 (IL-10), soluble tumor necrosis factor receptor 1 (sTNF-R1), and soluble tumor necrosis factor receptor 2 (sTNF-R2) were...

  7. Clinical significance of determination of semen plasma IL-2, IL-6, IL-8 and TNF-α contents in infertile males

    International Nuclear Information System (INIS)

    Sun Baoyi; Li Jun; Zhang Jiyun

    2004-01-01

    Objective: To explore the influence of high semen plasma contents of the cytokines (IL-2, IL-6, IL-8, TNF-α) on male fertility. Methods: Semen plasma levels of IL-2, IL-6, IL-8, and TNF-α were determined with RIA in 126 infertile and 20 fertile males. Results: Semen plasma contents of the 4 cytokines in infertile subjects were significantly higher than those in fertile ones (p 4/HP, n=15) had significantly higher contents of cytokines than those without leucocytospermia (WBC<4/HP, n=111). Besides, TNF-α contents in subjects with lower sperm activity and less motility rate as well as IL-8 contents in subjects with less sperm motility rate were both significantly higher than those in subjects with more normal sperms (p<0.01, p<0.05). Conclusion: High semen plasma cytokines contents represent existing local infection and enhanced auto-immune status, both damaging to sperms. Infertility would be the inevitable consequence. Monitoring of changes of the cytokine contents should be a part of fertility studies

  8. Allergic Rhinitis and Its Relationship with IL-10, IL-17, TGF-β, IFN-γ, IL 22, and IL-35

    Directory of Open Access Journals (Sweden)

    P. Bayrak Degirmenci

    2018-01-01

    Full Text Available Background. We aimed in our study to research the role of new cytokines such as IL-35, IL-22, and IL-17 that may form a target for novel treatment approaches. Methods. IL-10, IL-17, TGF-β, IFN-γ, IL-22, and IL-35 serum levels of allergic rhinitis (AR patients were measured using ELISA method. Allergic sensitization was demonstrated by the skin prick test. Patients only with olive tree sensitivity were evaluated for seasonal AR (SAR. Patients only with mite sensitivity were included in the study for perennial AR (PAR. AR clinic severity was demonstrated by the nasal symptom scores (NSS. Results. In total, 65 AR patients (patient group, having 31 PAR and 34 SAR patients, and 31 healthy individuals (control group participated in the study. Cytokine levels between the patient group and the control group were compared; IL-17 (p=0.038, IL-22 (p=0.001, and TGF-β (p=0.031 were detected as high in the patient group, and IFN-γ (p<0.001 was detected as low in the patient group. When correlation analysis was made between age, gender, prick test result, NSS, AR duration, and cytokine levels in the patient group, a negative correlation was detected only between IFN-γ (p=0.032/r=−0.266 level and NSS. Conclusions. Accompanied by the literature information, these results made us think that T cell subgroups and cytokines have an important role in AR immunopathogenesis. It is thought that future studies to be conducted relating to this subject will form new targets in treatment.

  9. Pattern of cytokine (IL-6 and IL-10) level as inflammation and anti-inflammation mediator of multiple organ dysfunction syndrome (MODS) in polytrauma.

    Science.gov (United States)

    Sapan, Heber Bombang; Paturusi, Idrus; Jusuf, Irawan; Patellongi, Ilhamjaya; Massi, Muh Nasrum; Pusponegoro, Aryono Djuned; Arief, Syafrie Kamsul; Labeda, Ibrahim; Islam, Andi Asadul; Rendy, Leo; Hatta, Mochammad

    2016-01-01

    Massive injury remains the most common cause of death for productive age group globally. The current immune, inflammatory paradigm, based on an incomplete understanding of the functional integration of the complex host response, remains a major impediment to the development of effective innovative diagnostic and therapeutic effort. This study attempt to investigate the pattern of inflammatory and anti-inflammatory cytokines such as interleukin-6 and 10 (IL-6 and IL-10) and their interaction in severe injury condition with its major complication as multiple organ dysfunction syndrome (MODS) and failure (MOF) after polytrauma. This is multicenter study held at 4 academic Level-1 Trauma center included 54 polytrauma participants. Inclusion criteria were age between 16-60 years old, had new acute episode of polytrauma which defined as injury in ≥2 body region with Injury Severity Score (ISS) ≥16, and the presence of Systemic Inflammation Response Syndrome (SIRS). Serum level of IL-6 and IL-10 were taken on day 2, 3, and 5 after trauma. During hospitalization, samples were observed for the occurrence of MODS or MOF using Sequential Organ Failure Assessment (SOFA) and mortality rate were also noted. Participant were mostly male with mean of age of 35, 9 years old, endured polytrauma caused by traffic accident. Elevation of cytokines (IL-6, IL-10, and IL-6/IL-10 ratio) had directly proportional with MODS and mortality. Threshold level of compensation for severe trauma is IL-6 of 50 pg/mL and trauma load of ISS ≥30. Inflammation reaction greater than this threshold level would result in downhill level of IL-6, IL-10, or IL-6/IL-10 ratio which associated with poor outcome (MODS and death). The elevation of these cytokines level were represent as compensation/adaptive immune system and its fall represent decompensating/failure of immune system after severe trauma. The pattern of IL-6 and IL-10 after polytrauma represent immune system effort to restore homeostasis

  10. Solubility of Two Vegetable Oils in Supercritical CO2

    Czech Academy of Sciences Publication Activity Database

    Sovová, Helena; Zarevúcka, Marie; Vacek, Miroslav; Stránský, Karel

    2001-01-01

    Roč. 20, č. 1 (2001), s. 15-28 ISSN 0896-8446 R&D Projects: GA ČR GA203/99/1457; GA ČR GA203/98/1445 Institutional research plan: CEZ:AV0Z4072921 Keywords : vegetable oil * supercritical CO2 * solubility Subject RIV: CI - Industrial Chemistry, Chemical Engineering Impact factor: 1.975, year: 2001

  11. Correlations between IL6 and the main clinical and biological parameters in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Mihaela Chicu

    2016-09-01

    Full Text Available Introduction: Cytokines are a family of complex peptide with hormone-like activity. They are soluble proteins without enzymatic activity and serves as the main intracellular mediators. Many cytokines achieves its effects by binding to special receptors membrane, and their adjustment is via soluble receptors. Cytokines are characterized by pleiotropism, overlapping and mutual adjustment. Proinflammatory cytokine involved in major rheumatoid arthritis are TNF, IL1α, IL1β, IL8.The biological effects of IL6 overlap in large part over those of TNF. If TNF is involved in induction of apoptosis or programmed cell death, IL6 is specifically associated with angiogenic factors activation and the occurrence of neovascularity to the synovium; favors articular cartilage degradation by increasing the release of MMP, decreasing PG, recruit osteoclasts, apoptosis of osteoblasts, release of degradative enzymes and the inflammatory mediators - iNOS, COX2 - TNF, IL6, IL8.Material and methods: Based on these data we proposed and realized – for the first time in Romania – the measurement of IL6 levels and the correlation with values of DAS28 score, HAQ, ESR, CRP, Hb and the immunological parameters too. The study was conducted on a group of 80 sick diagnosed with RA in various stages of evolution, under treatment with disease-modifying medication , type Methotrexate, Arava.Conclusions: Levels of IL-6 correlate a direct manner with those of acute phase reactants ,ESR, CRP and indirect values of Hb, IgG; the clinical parameters (number of tender and swollen joints, DAS28, HAQ are not influenced by values IL6.

  12. Correlation between serum IL-17A level and SALT score in patients with alopecia areata before and after NB-UVB therapy.

    Science.gov (United States)

    Morsy, Hanan; Maher, Reham; Negm, Dalia

    2018-06-01

    There is strong evidence that alopecia areata is of immunological background; Interleukin-17 (IL-17) is a Th17 pro-inflammatory cytokine that has been allied to the pathogenesis of different autoimmune and inflammatory diseases. This study aimed to measure serum IL-17A in patients with alopecia areata, and to study associations between IL-17A levels and disease severity before and after Narrowband-Ultraviolet B (NB-UVB), patient gender and age. Twenty patients with AA of the scalp were treated with (NB-UVB), and 15 healthy subjects' age and sex matched were enrolled as controls. Patients were assessed clinically by SALT score. Assay of serum levels of IL-17A by ELISA was done in patients and controls. The mean level of IL-17A was (15.63 Â ± 10.89 Pg/mL) in AA patient group, and (16.50 Â ± 5.02 Pg/mL) in control group. No statistically significant correlation was detected between SALT score and IL-17A level before (NB-UVB) treatment while a significant negative correlation between SALT score and IL-17A level was observed after treatment (r = -.448, P = .047). Mean SALT score for patients was (14.03 Â ± 13.48), and correlated positively with age (r = .446, P = .049). Although (NB-UVB) is an immune-modulatory type of treatment for alopecia areata of mild efficacy especially if it's used alone, it has shown significant decrease in serum IL-17A level among patients, and correlation to disease severity. © 2018 Wiley Periodicals, Inc.

  13. Clinical significance of changes of serum gas, IL-6 and IL-10 levels after treatment in patients with peptic ulcer

    International Nuclear Information System (INIS)

    Ye Yuexian

    2009-01-01

    Objective: To explore the clinical significance of changes of serum Gas, Interleukin-6(IL-6) and Interleukin-10(IL-10) levels in patients with peptic ulcer. Methods: Serum Gas, IL-6 and IL-10 (with RIA) levels were determined in 61 patients with peptic ulcer both before and after treatment as well as in 35 controls. Results: Before treatment the serum Gas, IL-6 and IL-10 levels were significantly higher in the patients with peptic ulcer than those in controls (P 0.05). Conclusion: Serum Gas, IL-6 and IL-10 levels were closely related to the diseases process of peptic ulcer and were of prognostic values. (authors)

  14. Intestinal DMBT1 expression is modulated by Crohn's disease-associated IL23R variants and by a DMBT1 variant which influences binding of the transcription factors CREB1 and ATF-2.

    Directory of Open Access Journals (Sweden)

    Julia Diegelmann

    Full Text Available OBJECTIVES: DMBT is an antibacterial pattern recognition and scavenger receptor. In this study, we analyzed the role of DMBT1 single nucleotide polymorphisms (SNPs regarding inflammatory bowel disease (IBD susceptibility and examined their functional impact on transcription factor binding and downstream gene expression. METHODS: Seven SNPs in the DMBT1 gene region were analyzed in 2073 individuals including 818 Crohn's disease (CD patients and 972 healthy controls in two independent case-control panels. Comprehensive epistasis analyses for the known CD susceptibility genes NOD2, IL23R and IL27 were performed. The influence of IL23R variants on DMBT1 expression was analyzed. Functional analysis included siRNA transfection, quantitative PCR, western blot, electrophoretic mobility shift and luciferase assays. RESULTS: IL-22 induces DMBT1 protein expression in intestinal epithelial cells dependent on STAT3, ATF-2 and CREB1. IL-22 expression-modulating, CD risk-associated IL23R variants influence DMBT1 expression in CD patients and DMBT1 levels are increased in the inflamed intestinal mucosa of CD patients. Several DMBT1 SNPs were associated with CD susceptibility. SNP rs2981804 was most strongly associated with CD in the combined panel (p = 3.0 × 10(-7, OR 1.42; 95% CI 1.24-1.63. All haplotype groups tested showed highly significant associations with CD (including omnibus P-values as low as 6.1 × 10(-18. The most strongly CD risk-associated, non-coding DMBT1 SNP rs2981804 modifies the DNA binding sites for the transcription factors CREB1 and ATF-2 and the respective genomic region comprising rs2981804 is able to act as a transcriptional regulator in vitro. Intestinal DMBT1 expression is decreased in CD patients carrying the rs2981804 CD risk allele. CONCLUSION: We identified novel associations of DMBT1 variants with CD susceptibility and discovered a novel functional role of rs2981804 in regulating DMBT1 expression. Our data suggest an important

  15. Intestinal DMBT1 expression is modulated by Crohn's disease-associated IL23R variants and by a DMBT1 variant which influences binding of the transcription factors CREB1 and ATF-2.

    Science.gov (United States)

    Diegelmann, Julia; Czamara, Darina; Le Bras, Emmanuelle; Zimmermann, Eva; Olszak, Torsten; Bedynek, Andrea; Göke, Burkhard; Franke, Andre; Glas, Jürgen; Brand, Stephan

    2013-01-01

    DMBT is an antibacterial pattern recognition and scavenger receptor. In this study, we analyzed the role of DMBT1 single nucleotide polymorphisms (SNPs) regarding inflammatory bowel disease (IBD) susceptibility and examined their functional impact on transcription factor binding and downstream gene expression. Seven SNPs in the DMBT1 gene region were analyzed in 2073 individuals including 818 Crohn's disease (CD) patients and 972 healthy controls in two independent case-control panels. Comprehensive epistasis analyses for the known CD susceptibility genes NOD2, IL23R and IL27 were performed. The influence of IL23R variants on DMBT1 expression was analyzed. Functional analysis included siRNA transfection, quantitative PCR, western blot, electrophoretic mobility shift and luciferase assays. IL-22 induces DMBT1 protein expression in intestinal epithelial cells dependent on STAT3, ATF-2 and CREB1. IL-22 expression-modulating, CD risk-associated IL23R variants influence DMBT1 expression in CD patients and DMBT1 levels are increased in the inflamed intestinal mucosa of CD patients. Several DMBT1 SNPs were associated with CD susceptibility. SNP rs2981804 was most strongly associated with CD in the combined panel (p = 3.0 × 10(-7), OR 1.42; 95% CI 1.24-1.63). All haplotype groups tested showed highly significant associations with CD (including omnibus P-values as low as 6.1 × 10(-18)). The most strongly CD risk-associated, non-coding DMBT1 SNP rs2981804 modifies the DNA binding sites for the transcription factors CREB1 and ATF-2 and the respective genomic region comprising rs2981804 is able to act as a transcriptional regulator in vitro. Intestinal DMBT1 expression is decreased in CD patients carrying the rs2981804 CD risk allele. We identified novel associations of DMBT1 variants with CD susceptibility and discovered a novel functional role of rs2981804 in regulating DMBT1 expression. Our data suggest an important role of DMBT1 in CD pathogenesis.

  16. Differential baseline and response profile to IFN-γ gene transduction of IL-6/IL-6 receptor-α secretion discriminate primary tumors versus bone marrow metastases of nasopharyngeal carcinomas in culture

    International Nuclear Information System (INIS)

    Chou, Andy Shau-Bin; Wang, Hsin-Yi; Chen, Hung-Chang; Tsai, Ming-Hsiu; Chuang, Cheng-Keng; Liao, Shuen-Kuei

    2009-01-01

    marginal levels of IFN-γ (8.4 ~ 10.5 pg/ml), could be enhanced to produce higher levels of IFN-γ (6.8- to 10.3-fold increase) after IFN-γ transduction. Unlike P-NPCs, BM-NPCs spontaneously released IFN-γ at moderate levels (83.8 ~ 100.7 pg/ml), which were enhanced by 1.3- to 2.2-fold in the spent media of their IFN-γ-transduced counterparts. Our results showed that cultured P-NPCs and BM-NPCs could be distinguished from one another on the basis of their differential baseline secretion pattern of IFN-γ, IL-6 and IL-6Rα, and their differential response profiles to IFN-γ gene transfer of the production of these three soluble molecules. These results suggest that the IL-6 and IFN-γ pathways in a background of genetic instability be involved in the acquisition of metastatic behaviour in BM-NPCs

  17. IL-12 and IL-23 modulate plasticity of FoxP3+ regulatory T cells in human Leprosy.

    Science.gov (United States)

    Tarique, Mohd; Saini, Chaman; Naqvi, Raza Ali; Khanna, Neena; Sharma, Alpana; Rao, D N

    2017-03-01

    Leprosy is a bacterial disease caused by M. leprae. Its clinical spectrum reflects the host's immune response to the M. leprae and provide an ideal model to investigate the host pathogen interaction and immunological dysregulation. Tregs are high in leprosy patients and responsible for immune suppression of the host by producing IL-10 and TGF-β cytokines. In leprosy, plasticity of Tregs remain unstudied. This is the first study describing the conversion of Tregs into Th1-like and Th17-like cells using in vitro cytokine therapy in leprosy patients. Peripheral blood mononuclear cells from leprosy patients were isolated and stimulated with M. leprae antigen (MLCwA), rIL-12 and rIL-23 for 48h. Expression of FoxP3 in CD4 + CD25 + Tregs, intracellular cytokines IFN-γ, TGF-β, IL-10 and IL-17 in Tregs cells were evaluated by flow cytometry (FACS) after stimulation. rIL-12 treatment increases the levels of pStat4 in Tregs and IFN-γ production. In the presence of rIL-23, pStat3 + and IL-17A + cells increase. rIL-12 and r-IL-23 treatment downregulated the FoxP3 expression, IL-10 and TGF-β production by Tregs and enhances the expression of co-stimulatory molecules (CD80, CD86). In conclusion rIL-12 converts Tregs into IFN-γ producing cells through STAT-4 signaling while rIL-23 converts Tregs into IL-17 producing cells through STAT-3 signaling in leprosy patients. This study may helpful to provide a new avenue to overcome the immunosuprression in leprosy patients using in vitro cytokine. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Inhibition of IL-1R1/MyD88 signalling promotes mesenchymal stem cell-driven tissue regeneration.

    Science.gov (United States)

    Martino, Mikaël M; Maruyama, Kenta; Kuhn, Gisela A; Satoh, Takashi; Takeuchi, Osamu; Müller, Ralph; Akira, Shizuo

    2016-03-22

    Tissue injury and the healing response lead to the release of endogenous danger signals including Toll-like receptor (TLR) and interleukin-1 receptor, type 1 (IL-1R1) ligands, which modulate the immune microenvironment. Because TLRs and IL-1R1 have been shown to influence the repair process of various tissues, we explored their role during bone regeneration, seeking to design regenerative strategies integrating a control of their signalling. Here we show that IL-1R1/MyD88 signalling negatively regulates bone regeneration, in the mouse. Furthermore, IL-1β which is released at the bone injury site, inhibits the regenerative capacities of mesenchymal stem cells (MSCs). Mechanistically, IL-1R1/MyD88 signalling impairs MSC proliferation, migration and differentiation by inhibiting the Akt/GSK-3β/β-catenin pathway. Lastly, as a proof of concept, we engineer a MSC delivery system integrating inhibitors of IL-1R1/MyD88 signalling. Using this strategy, we considerably improve MSC-based bone regeneration in the mouse, demonstrating that this approach may be useful in regenerative medicine applications.

  19. Association between IL28B polymorphism, TNFα and biomarkers of insulin resistance in chronic hepatitis C-related insulin resistance.

    Science.gov (United States)

    Lemoine, M; Chevaliez, S; Bastard, J P; Fartoux, L; Chazouillères, O; Capeau, J; Pawlotsky, J M; Serfaty, L

    2015-11-01

    TNFα has been shown to play a role in hepatitis C virus (HCV)-induced insulin resistance (IR). Polymorphism of the IL28B gene that encodes IFN-lambda 3 may be associated with IR through modulation of TNFα. The aim of this study was to investigate the relationship between IL28B rs12979860 genotype, the level of TNFα activation and the degree of IR in patients with chronic hepatitis C. One hundred and thirty-three nondiabetic genotype 1 HCV-infected patients with biopsy proven noncirrhotic hepatitis C were investigated for IR (using HOMA index), IL28B rs12979860 genotype and fasting circulating levels of soluble receptor 1 of TNFα (sTNFR1) and adipokines: leptin, adiponectin and IL-6. The HOMA-IR was positively correlated with serum levels of leptin (r = 0.35, P < 0.0001) and sTNFR1 (r = 0.35, P < 0.0001) but not with IL-6 or adiponectin. IL28B rs12979860 CC genotype was observed in 35% patients. Genotype CC and nongenotype CC patients were similar in terms of HOMA-IR (means 1.6 ± 0.9 vs 1.7 ± 1.4) and had similar circulating levels of sTNFR1 and adipokines. Independent factors associated with IR were ferritin (OR = 1.002, P = 0.02), leptin (OR = 1.06, P = 0.02) and sTNFR1 (OR = 7.9, P = 0.04). This study suggests that in nondiabetic, noncirrhotic, HCV genotype 1-infected patients, there is no relationship between IL28B rs12979860 genotype and HOMA-IR or sTNFR1 level. HCV-related IR may be mediated through TNFα independent of IL28B genotype. © 2015 John Wiley & Sons Ltd.

  20. Association of Neuropeptide Y (NPY), Interleukin-1B (IL1B) Genetic Variants and Correlation of IL1B Transcript Levels with Vitiligo Susceptibility

    Science.gov (United States)

    Laddha, Naresh C.; Dwivedi, Mitesh; Mansuri, Mohmmad Shoab; Singh, Mala; Patel, Hetanshi H.; Agarwal, Nishtha; Shah, Anish M.; Begum, Rasheedunnisa

    2014-01-01

    Background Vitiligo is a depigmenting disorder resulting from loss of functional melanocytes in the skin. NPY plays an important role in induction of immune response by acting on a variety of immune cells. NPY synthesis and release is governed by IL1B. Moreover, genetic variability in IL1B is reported to be associated with elevated NPY levels. Objectives Aim of the present study was to explore NPY promoter −399T/C (rs16147) and exon2 +1128T/C (rs16139) polymorphisms as well as IL1B promoter −511C/T (rs16944) polymorphism and to correlate IL1B transcript levels with vitiligo. Methods PCR-RFLP method was used to genotype NPY -399T/C SNP in 454 patients and 1226 controls; +1128T/C SNP in 575 patients and 1279 controls and IL1B −511C/T SNP in 448 patients and 785 controls from Gujarat. IL1B transcript levels in blood were also assessed in 105 controls and 95 patients using real-time PCR. Results Genotype and allele frequencies for NPY −399T/C, +1128T/C and IL1B −511C/T SNPs differed significantly (pvitiligo by 2.3 fold (pvitiligo (p = 0.015), also in female patients than male patients (p = 0.026). Genotype-phenotype correlation showed moderate association of IL1B -511C/T polymorphism with higher IL1B transcript levels. Trend analysis revealed significant difference between patients and controls for IL1B transcript levels with respect to different genotypes. Conclusion Our results suggest that NPY −399T/C, +1128T/C and IL1B −511C/T polymorphisms are associated with vitiligo and IL1B −511C/T SNP influences its transcript levels leading to increased risk for vitiligo in Gujarat population. Up-regulation of IL1B transcript in patients advocates its possible role in autoimmune pathogenesis of vitiligo. PMID:25221996

  1. Effects of exogenous and endogenous IL-2 on irradiated human peripheral blood lymphocytes

    International Nuclear Information System (INIS)

    Zhang Lansheng; Wang Ninghai; Luan Meiling

    1993-08-01

    Human peripheral blood lymphocytes were irradiated with 1 to 40 Gy of γ-ray, and then cultured with PHA to prepare supernatant containing IL-2 for observation of kinetics of endogenous IL-2 production and reversion of lymphocyte proliferation after adding a highly purified IL-2. IL-2 activity was determined by the ability to sustain IL-2 dependent cell line (CTLL), lymphocyte proliferation was determined by 3 H-TdR incorporation and T lymphocyte subsets by monoclonal antibodies. The experimental results showed that lymphocytes exposed to 60 Co synthesized less DNA than nonirradiated lymphocytes. The inhibitory effect can partially reversed by purified IL-2 at the γ-ray dose range of 1 to 10 Gy, while irradiation with 2.5 Gy resulted in a reduction of T cells and T subsets, and increase in CD + 4 /CD + 8 ratio. The ratio of subsets recovered after adding IL-2. The kinetics of IL-2 production showed that the endogenous IL-2 production rose markedly with increasing dose of irradiation at the range of 1 to 10 Gy, and the peak of IL-2 production was at the γ-ray dose of 10 Gy

  2. Clinical significance of the changes of serum IL-8 and IL-12 levels in pediatric patients with anaphylactoid purpura (AP)

    International Nuclear Information System (INIS)

    Liang Zhenming; Liu Xia

    2005-01-01

    Objective: To explore the role of IL-8 and IL-12 in the pathogenesis of anaphylactoid purpura (AP) and anaphylactoid purpura nephritis (APN). Methods: Serum IL-8 (with RIA) and IL-12 (with ELISA) levels were measured in 32 pediatric patients with anaphylactoid purpura (AP), 11 pediatric patients with anaphylactoid purpura nephritis (APN) and 15 controls. Results: During acute stage, serum IL-8 and IL-12 levels in both the AP and APN patients were significantly higher than those in controls and remained higher during convalescence. IL-8 and IL-12 levels were mutually positively correlated in acute stage. Conclusion: IL-8 and IL-12 participated in the pathogenesis of AP and APN. Theoretically, antagonist to those cytokines might be of clinical benefits. (authors)

  3. Elevated levels of IL-6 and IL-18 in manic and hypomanic states in rapid cycling bipolar disorder patients

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Weikop, Pia; Kessing, Lars Vedel

    2015-01-01

    obtained in affective states of varying polarity during 6-12 months in 37 rapid cycling bipolar disorder patients and compared with repeated measurements in 40 age- and gender matched healthy control subjects, using rigorous laboratory-, clinical- and statistical methodology. Adjusting for demographical...... were to assess alterations of peripheral cytokine levels between affective states in rapid cycling bipolar disorder patients and to compare these with levels in healthy control subjects. In a longitudinal design, repeated measurements of plasma levels of IL-6, IL-10, IL-18, IL-1β and TNF-α were......, clinical- and lifestyle factors, levels of IL-6 (prapid cycling bipolar disorder patients in a manic/hypomanic state, compared with a depressed and a euthymic state. Compared with healthy control subjects, unadjusted levels of IL-6 (p

  4. Tissue Expressions of Soluble Human Epoxide Hydrolase-2 Enzyme in Patients with Temporal Lobe Epilepsy.

    Science.gov (United States)

    Ahmedov, Merdin Lyutviev; Kemerdere, Rahsan; Baran, Oguz; Inal, Berrin Bercik; Gumus, Alper; Coskun, Cihan; Yeni, Seher Naz; Eren, Bulent; Uzan, Mustafa; Tanriverdi, Taner

    2017-10-01

    We sought to simply demonstrate how levels of soluble human epoxide hydrolase-2 show changes in both temporal the cortex and hippocampal complex in patients with temporal lobe epilepsy. A total of 20 patients underwent anterior temporal lobe resection due to temporal lobe epilepsy. The control group comprised 15 people who died in traffic accidents or by falling from a height, and their autopsy findings were included. Adequately sized temporal cortex and hippocampal samples were removed from each patient during surgery, and the same anatomic structures were removed from the control subjects during the autopsy procedures. Each sample was stored at -80°C as rapidly as possible until the enzyme assay. The temporal cortex in the epilepsy patients had a significantly higher enzyme level than did the temporal cortex of the control group (P = 0.03). Correlation analysis showed that as the enzyme level increases in the temporal cortex, it also increases in the hippocampal complex (r 2  = 0.06, P = 0.00001). More important, enzyme tissue levels showed positive correlations with seizure frequency in both the temporal cortex and hippocampal complex in patients (r 2  = 0.7, P = 0.00001 and r 2  = 0.4, P = 0.003, respectively). The duration of epilepsy was also positively correlated with the hippocampal enzyme level (r 2  = 0.06, P = 0.00001). Soluble human epoxy hydrolase enzyme-2 is increased in both lateral and medial temporal tissues in temporal lobe epilepsy. Further studies should be conducted as inhibition of this enzyme has resulted in a significant decrease in or stopping of seizures and attenuated neuroinflammation in experimental epilepsy models in the current literature. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Clinical significance of changes of serum hs-CRP, IL-6 and TNF-α levels after treatment in patients with polycystic ovary syndrome

    International Nuclear Information System (INIS)

    Yang Wen; Wang Ying

    2010-01-01

    Objective: To explore the clinical significance of changes of serum hs-CRP, IL-6 and TNF-α levels in patients with polycystic ovary syndrome. Methods: Serum hs-CRP (with immuno turbidity method), IL-6, TNF-α (with RIA) levels were determined in 31 patients with polycystic ovary syndrome both before and after six, month's treatment as well as 35 controls. Results: Before treatment, the serum hs-CRP, IL-6 and TNF-α levels in the 31 patients with polycystic ovary syndrome were significantly higher than those in controls (P 0.05). Serum hs-CRP levels were positive correlate with serum IL-6, TNF-α levels (r=0.6014, 0.5982, P<0.01). Conclusion: Serum hs-CRP, IL-6 and TNF-α levels were correlated to the development of polycystic ovary syndrome (PCOS). (authors)

  6. Identification of potential small molecule allosteric modulator sites on IL-1R1 ectodomain using accelerated conformational sampling method.

    Directory of Open Access Journals (Sweden)

    Chao-Yie Yang

    Full Text Available The interleukin-1 receptor (IL-1R is the founding member of the interleukin 1 receptor family which activates innate immune response by its binding to cytokines. Reports showed dysregulation of cytokine production leads to aberrant immune cells activation which contributes to auto-inflammatory disorders and diseases. Current therapeutic strategies focus on utilizing antibodies or chimeric cytokine biologics. The large protein-protein interaction interface between cytokine receptor and cytokine poses a challenge in identifying binding sites for small molecule inhibitor development. Based on the significant conformational change of IL-1R type 1 (IL-1R1 ectodomain upon binding to different ligands observed in crystal structures, we hypothesized that transient small molecule binding sites may exist when IL-1R1 undergoes conformational transition and thus suitable for inhibitor development. Here, we employed accelerated molecular dynamics (MD simulation to efficiently sample conformational space of IL-1R1 ectodomain. Representative IL-1R1 ectodomain conformations determined from the hierarchy cluster analysis were analyzed by the SiteMap program which leads to identify small molecule binding sites at the protein-protein interaction interface and allosteric modulator locations. The cosolvent mapping analysis using phenol as the probe molecule further confirms the allosteric modulator site as a binding hotspot. Eight highest ranked fragment molecules identified from in silico screening at the modulator site were evaluated by MD simulations. Four of them restricted the IL-1R1 dynamical motion to inactive conformational space. The strategy from this study, subject to in vitro experimental validation, can be useful to identify small molecule compounds targeting the allosteric modulator sites of IL-1R and prevent IL-1R from binding to cytokine by trapping IL-1R in inactive conformations.

  7. IL23R in the Swedish, Finnish, Hungarian and Italian populations: association with IBD and psoriasis, and linkage to celiac disease

    Directory of Open Access Journals (Sweden)

    Vatta Serena

    2009-01-01

    Full Text Available Abstract Background Association of the interleukin-23 receptor (IL23R with inflammatory bowel disease (IBD has been confirmed in several populations. IL23R also associates with psoriasis, suggesting that the gene may be an important candidate for many chronic inflammatory diseases. Methods We studied association of single-nucleotide variants in IL23R with IBD in Swedish patients, in both Crohn's disease (CD and ulcerative colitis (UC subsets. The same genetic variants were also studied in Finnish patients with psoriasis or celiac disease, and in Hungarian and Italian patients with celiac disease. Results Association of IL23R with IBD was replicated in our Swedish patients, and linkage and association of the IL23R region with psoriasis was found in the Finnish population. The IL23R region was also linked to celiac disease in Finnish families, but no association of IL23R variants with celiac disease was found in the Finnish, Hungarian or Italian samples. Conclusion Our study is the first to demonstrate association of IL23R with CD and UC in Swedish patients with IBD. It is also the first study to report linkage and association of the IL23R region with psoriasis in the Finnish population. Importantly, this is the first report of linkage of the IL23R region to celiac disease, a chronic inflammatory condition in which IL23R has not been previously implicated.

  8. Circulating soluble Fas levels and risk of ovarian cancer

    International Nuclear Information System (INIS)

    Akhmedkhanov, Arslan; Lenner, Per; Muti, Paola; Rinaldi, Sabina; Kaaks, Rudolf; Berrino, Franco; Hallmans, Göran; Toniolo, Paolo; Lundin, Eva; Guller, Seth; Lukanova, Annekatrin; Micheli, Andrea; Ma, Yuehong; Afanasyeva, Yelena; Zeleniuch-Jacquotte, Anne; Krogh, Vittorio

    2003-01-01

    Dysregulation of apoptosis, specifically overexpression of soluble Fas (sFas), has been proposed to play a role in the development of ovarian cancer. The main objective of the present study was to evaluate serum sFas as a potential biomarker of ovarian cancer risk. The association between serum sFas levels and the risk of ovarian cancer was examined in a case-control study nested within three prospective cohorts in New York (USA), Umeå (Sweden), and Milan (Italy). Case subjects were 138 women with primary invasive epithelial ovarian cancer diagnosed between 2 months and 13.2 years after the initial blood donation. Control subjects were 263 women who were free of cancer, and matched the case on cohort, menopausal status, age, and enrollment date. Serum sFas levels were determined using a quantitative sandwich enzyme immunoassay. Serum sFas levels were similar in women subsequently diagnosed with ovarian cancer (median, 6.5 ng/mL; range, 4.4 – 10.2) and in controls (median, 6.8 ng/mL; range, 4.5 – 10.1). Statistically significant trends of increasing serum sFas with age were observed among cases (r = 0.39, p < 0.0001) and controls (r = 0.42, p < 0.0001). Compared to women in the lowest third, women in the highest third of serum sFas were not at increased risk of ovarian cancer after adjustment for potential confounders (odd ratio (OR), 0.87; 95% confidence interval (CI), 0.42 – 1.82). The results suggest that serum sFas may not be a suitable marker for identification of women at increased risk of ovarian cancer

  9. The IL23R A/Gln381 allele promotes IL-23 unresponsiveness in human memory T-helper 17 cells and impairs Th17 responses in psoriasis patients.

    Science.gov (United States)

    Di Meglio, Paola; Villanova, Federica; Napolitano, Luca; Tosi, Isabella; Terranova Barberio, Manuela; Mak, Rose K; Nutland, Sarah; Smith, Catherine H; Barker, Jonathan N W N; Todd, John A; Nestle, Frank O

    2013-10-01

    We and others have shown that the minor, nonconserved allele Gln381 of the Arg381Gln single-nucleotide polymorphism (rs11209026G>A) of the IL-23 receptor gene (IL23R) protects against psoriasis. Moreover, we have recently shown impaired IL-23-induced IL-17A production and STAT-3 phosphorylation in Th17 cells generated in vitro from healthy individuals heterozygous for the protective A allele (GA). However, the biological effect of this variant has not been determined in homozygous carriers of the protective A allele (AA), nor in psoriatic patients. Here we expand our functional investigation of the IL23R Arg381Gln gene variant to include AA homozygous individuals. By using isolated memory CD4+ T cells, we found attenuated IL-23-induced Th17 response in heterozygous individuals. Moreover, we found that AA homozygous individuals were strikingly unresponsive to IL-23, with minimal or no IL-17A and IL-17F production and failure of human memory Th17 cell survival/expansion. Finally, IL-23-induced Th17 response was also attenuated in age- and sex-matched GA versus GG psoriatic patients undergoing systemic treatment. Taken together, our data provide evidence for an allele-dosage effect for IL-23R Gln381 and indicate that common gene alleles associated with complex diseases might have biological effects of considerable magnitude in homozygous carriers.

  10. The rs7517847 polymorphism in the IL-23R gene is associated with gout in a Chinese Han male population.

    Science.gov (United States)

    Liu, Shiguo; He, Hongmei; Yu, Renchao; Han, Lin; Wang, Can; Cui, Ying; Li, Changgui

    2015-05-01

    Gout is a polygenic auto-inflammatory disease, in which inflammation plays an important role in disease pathogenesis. The cytokine interleukin (IL)-23 promotes inflammation and helps to guide inflammatory cells, while studies have shown that the IL-23R gene is associated with susceptibility to several immune-related diseases. This study aimed to determine whether the IL-23R rs7517847 (G/T) polymorphism is associated with gout in a Chinese Han male population. We recruited 400 patients with gout and 582 gout-free controls. After obtaining blood samples for DNA extraction, genotyping of the rs7517847 polymorphism was performed by fluorescence-based quantitative PCR using TaqMan probes. An association analysis was carried out using the χ(2) test. A genotype-phenotype analysis was also conducted. Both genotypic and allelic frequencies of rs7517847 differed significantly between gout patients and controls (χ(2) = 6.792, df = 2, P = 0.034 by genotype; χ(2) = 4.202, df = 1, P = 0.04 by allele). IL-23R may be associated with gout in a Chinese Han male population, although our findings should be confirmed using larger sample sizes and other independent populations.

  11. Recombinant Nonstructural 3 Protein, rNS3, of Hepatitis C Virus Along With Recombinant GP96 Induce IL-12, TNFα and α5integrin Expression in Antigen Presenting Cells

    Science.gov (United States)

    Hajizadeh, Mohammad Reza; Mokarram, Pooneh; Kamali sarvestani, Eskandar; Bolhassani, Azam; Mostafavi Pour, Zohreh

    2013-01-01

    Background Hepatitis C virus (HCV) infection is the main cause of chronic liver disease and to date there has been no vaccine development to prevent this infection. Among non-structural HCV proteins, NS3 protein is an excellent goal for a therapeutic vaccine, due to its large size and less variation in conserved regions. The immunogenic properties of heat shock proteins (HSPs) for instance GP96 have prompted investigations into their function as strong adjuvant to improve innate and adaptive immunity. Objectives The aim of this study was to examine additive effects of recombinant GP96 (rGP96) fragments accompanied by rNS3 on expression levels of α5integrin and pro-inflammatory cytokines, IL-12 and TNFα, in Antigen Presenting Cells (APCs). Materials and Methods Recombinant viral proteins (rNS3 and rRGD-NS3), N-terminal and C-terminal fragments of GP96 were produced and purified from E. coli in order to treat the cells; mouse spleen Dendritic Cells (DCs) and THP-1 macrophages. Results Our results showed that rNT-GP96 alone significantly increases the expression level of IL-12, TNFα and α5integrin in THP-1 macrophages and DCs, while IL-12 and TNFα expression levels were unaffected by either rNS3 or rRGD-NS3. Interestingly, the co-addition of these recombinant proteins with rNT-GP96 increased IL-12, TNFα and α5integrin expression. Pearson Correlation showed a direct association between α5integrin with IL-12 and TNF-α expression. Conclusions we have highlighted the role of rNS3 plus rNT-GP96 mediated by α5integrin in producing IL-12 and TNFα. It can be suggested that rNT-GP96 could enhance immunity characteristic of rNS3 protein via production of pro-inflammatory cytokines. PMID:24032046

  12. Evaluation of IL-1β, IL-1ra, and IL-10 levels and outcome of periodontal therapy in chronic periodontitis with familial Mediterranean fever.

    Science.gov (United States)

    Bostanci, Vildan; Toker, Hulya; Senel, Soner; Poyraz, Omer; Akpinar, Aysun; Görgün, Emine Pirim; Bakar, Olcay

    2017-01-01

    This study aimed to examine the IL-1β, IL-1ra, and IL-10 cytokine levels in gingival crevicular fluid (GCF) and serum of familial Mediterranean fever (FMF) and chronic periodontitis (CP) patients, and their response to nonsurgical periodontal therapy. A total of 50 patients, 15 FMF patients with generalized chronic periodontitis (FMF-CP), 15 systemically healthy patients with generalized chronic periodontitis (CP), ten systemically and periodontal healthy controls (HC), and ten periodontally healthy FMF patients (FMF-HC) were enrolled in the study. The cytokine levels in GCF and serum were determined by ELISA. Probing depth, clinical attachment level, and gingival and plaque indices in each participant were also measured. The GCF and clinical parameters at baseline and 6 weeks were recorded. The study indicated statistically significant healing of the clinical parameters in both FMF-CP and CP groups after periodontal treatment. GCF IL-1β levels at 6 weeks in FMF-CP group were significantly lower than the CP group (p  0.05). The results of our study suggested that there was a positive correlation between gingival inflammation and serum cytokine levels in FMF patients and also colchicine treatment showed protective effects on GCF cytokine levels in FMF-CP group. Following treatment, GCF IL-1β and GCF IL-1ra levels were decreased in FMF-CP group. GCF IL-10 levels were increased in FMF-CP group compared to other groups. Also, the serum cytokine levels associated with periodontal inflammation in FMF patients.

  13. AHR prevents human IL-1R1hi ILC3 differentiation to natural killer cells

    Science.gov (United States)

    Hughes, Tiffany; Briercheck, Edward L.; Freud, Aharon G.; Trotta, Rossana; McClory, Susan; Scoville, Steven D.; Keller, Karen; Deng, Youcai; Cole, Jordan; Harrison, Nicholas; Mao, Charlene; Zhang, Jianying; Benson, Don M.; Yu, Jianhua; Caligiuri, Michael A.

    2014-01-01

    SUMMARY Accumulating evidence indicates that human natural killer (NK) cells develop in secondary lymphoid tissue (SLT) through a so-called “stage 3” developmental intermediate minimally characterized by a CD34-CD117+CD94- immunophenotype that lacks mature NK cell function. This stage 3 population is heterogeneous, potentially composed of functionally distinct innate lymphoid cell (ILC) types that includes interleukin-1 receptor (IL-1R1) positive, IL-22-producing ILC3s. Whether human ILC3s are developmentally related to NK cells is a subject of ongoing investigation. Here we show that antagonism of the aryl hydrocarbon receptor (AHR) or silencing of AHR gene expression promotes differentiation of tonsillar IL-22-producing IL-1R1hi human ILC3s to CD56brightCD94+ IFN-gamma-producing cytolytic mature NK cells expressing eomesodermin (EOMES) and T-Box Protein 21 (TBX21 or TBET). Hence, AHR is a transcription factor that prevents human IL-1R1hi ILC3s from differentiating into NK cells. PMID:24953655

  14. Identification of Interleukin-27 (IL-27)/IL-27 Receptor Subunit Alpha as a Critical Immune Axis for In Vivo HIV Control.

    Science.gov (United States)

    Ruiz-Riol, M; Berdnik, D; Llano, A; Mothe, B; Gálvez, C; Pérez-Álvarez, S; Oriol-Tordera, B; Olvera, A; Silva-Arrieta, S; Meulbroek, M; Pujol, F; Coll, J; Martinez-Picado, J; Ganoza, C; Sanchez, J; Gómez, G; Wyss-Coray, T; Brander, C

    2017-08-15

    Intact and broad immune cell effector functions and specific individual cytokines have been linked to HIV disease outcome, but their relative contribution to HIV control remains unclear. We asked whether the proteome of secreted cytokines and signaling factors in peripheral blood can be used to discover specific pathways critical for host viral control. A custom glass-based microarray, able to measure >600 plasma proteins involved in cell-to-cell communication, was used to measure plasma protein profiles in 96 HIV-infected, treatment-naive individuals with high (>50,000) or low (HIV RNA copies/ml) viral loads. Univariate and regression model analysis demonstrate that plasma levels of soluble interleukin-27 (IL-27) are significantly elevated in individuals with high plasma viremia ( P HIV-DNA copy numbers in peripheral blood mononuclear cells (PBMC) (Rho = 0.4011; P = 0.0027). Moreover, soluble IL-27 plasma levels are negatively associated with the breadth and magnitude of the total virus-specific T-cell responses and directly with plasma levels of molecules involved in Wnt/β-catenin signaling. In addition to IL-27, gene expression levels of the specific IL-27 receptor ( IL27RA ) in PBMC correlated directly with both plasma viral load (Rho = 0.3531; P = 0.0218) and the proviral copy number in the peripheral blood as an indirect measure of partial viral reservoir (Rho = 0.4580; P = 0.0030). These results were validated in unrelated cohorts of early infected subjects as well as subjects before and after initiation of antiretroviral treatment, and they identify IL-27 and its specific receptor as a critical immune axis for the antiviral immune response and as robust correlates of viral load and proviral reservoir size in PBMC. IMPORTANCE The detailed knowledge of immune mechanisms that contribute to HIV control is a prerequisite for the design of effective treatment strategies to achieve HIV cure. Cells communicate with each other by secreting signaling proteins, and

  15. Effect of Proinflammatory Cytokines (IL-6, TNF-α, and IL-1β on Clinical Manifestations in Indian SLE Patients

    Directory of Open Access Journals (Sweden)

    Vinod Umare

    2014-01-01

    Full Text Available Systemic lupus erythematosus (SLE is an inflammatory rheumatic disease characterized by production of autoantibodies and organ damage. Elevated levels of cytokines have been reported in SLE patients. In this study we have investigated the effect of proinflammatory cytokines (IL-6, TNF-α, and IL-1β on clinical manifestations in 145 Indian SLE patients. One hundred and forty-five healthy controls of the same ethnicity served as a control group. Clinical disease activity was scored according to SLEDAI score. Accordingly, 110 patients had active disease and 35 patients had inactive disease. Mean levels of IL-6, TNF-α, and IL-1β were found to be significantly higher in SLE patients than healthy controls (P<0.001. Mean level of IL-6 for patients with active disease (70.45±68.32 pg/mL was significantly higher (P=0.0430 than those of inactive disease patients (43.85±63.36 pg/mL. Mean level of TNF-α was 44.76±68.32 pg/mL for patients with active disease while it was 25.97±22.03 pg/mL for those with inactive disease and this difference was statistically significant (P=0.0161. Similar results were obtained for IL-1β (P=0.0002. Correlation between IL-6, TNF-α, and IL-1β serum levels and SLEDAI score was observed (r=0.20, r=0.27, and r=0.38, resp.. This study supports the role of these proinflammatory cytokines as inflammatory mediators in active stage of disease.

  16. Clinical significance of measurement of serum IL-8, IL-1β and TNF-α levels after treatment in patients with periodontitis

    International Nuclear Information System (INIS)

    Wang Tongwu

    2009-01-01

    Objective: To explore the significance of changes of serum IL-8, IL-1β and TNF-α levels after treatment in patients with periodontitis. Methods: Serum IL-8, IL-1β and TNF-α(with RIA) levels were determined in 36 patients with periodontitis both before and after treatment as well as in 35 controls. Results: Before treatment, serum IL-8, IL-1β and TNF-α levels were significantly higher in the patients than those in controls (P 0.05). Conclusion: Detection of serum IL-8, IL-1β and TNF-α levels might reflect the progress of disease in patients with periodontitis and might be of important clinical value. (authors)

  17. Diagnostic value of combined determination of serum and chest fluid adenosine deaminase (ADA), IL-2, IL-6, IL-10 contents for differentiation of tuberculous from malignant pleural effusion

    International Nuclear Information System (INIS)

    Wu Jiaming; Wang Limin

    2005-01-01

    Objective: To investigate the possible diagnostic value of combined determination of serum and chest fluid contents of ADA, IL-2, IL-6, IL-10 in patients with tuberculous and malignant pleural effusion. Methods: Serum and chest fluid ADA (with biochemical method), IL-2, IL-6, IL-10 (with ELISA) contents were measured in 56 patients with tuberculosis pleural effusion, 53 patients with malignant effusion and 30 controls (in serum only). The receiving operative characteristic (ROC) curve for each parameter was analyzed for study of respective area under curse (Auc). Results: The serum IL-6 levels in both groups of patients were significantly higher than those in the controls (P<0.05). The chest fluid contents of ADA, IL-2, IL-6 and IL-10 in patients with tuberculous effusion were all significantly higher than those in patients with malignancies (P<0.05). The Auc in the ROC was largest in the case of ADA, followed by IL-10, IL-6 with IL-2 the least. Conclusion: Determination of chest fluid ADA, IL-2, IL-6, IL-10 contents was helpful in the differentiation of tuberculous from malignant pleural effusion. Combined determination of chest fluid ADA and IL-10 provided the highest accuracy rate for differentional diagnosis. (authors)

  18. Identification of NR4A2 as a transcriptional activator of IL-8 expression in human inflammatory arthritis.

    LENUS (Irish Health Repository)

    Aherne, Carol M

    2009-10-01

    Expression of the orphan nuclear receptor NR4A2 is controlled by pro-inflammatory mediators, suggesting that NR4A2 may contribute to pathological processes in the inflammatory lesion. This study identifies the chemoattractant protein, interleukin 8 (IL-8\\/CXCL8), as a molecular target of NR4A2 in human inflammatory arthritis and examines the mechanism through which NR4A2 modulates IL-8 expression. In TNF-alpha-activated human synoviocyte cells, enhanced expression of IL-8 mRNA and protein correspond to temporal changes in NR4A2 transcription and nuclear distribution. Ectopic expression of NR4A2 leads to robust changes in endogenous IL-8 mRNA levels and co-treatment with TNF-alpha results in significant (p<0.001) secretion of IL-8 protein. Transcriptional effects of NR4A2 on the human IL-8 promoter are enhanced in the presence of TNF-alpha, suggesting molecular crosstalk between TNF-alpha signalling and NR4A2. A dominant negative IkappaB kinase antagonizes the combined effects of NR4A2 and TNF-alpha on IL-8 promoter activity. Co-expression of NR4A2 and the p65 subunit of NF-kappaB enhances IL-8 transcription and functional studies indicate that transactivation occurs independently of NR4A2 binding to DNA or heterodimerization with additional nuclear receptors. The IL-8 minimal promoter region is sufficient to support NR4A2 and NF-kappaB\\/p65 co-operative activity and NR4A2 can interact with NF-kappaB\\/p65 on a 39bp sequence within this region. In patients treated with methotrexate for active inflammatory arthritis, a reduction in NR4A2 synovial tissue levels correlate significantly (n=10, r=0.73, p=0.002) with changes in IL-8 expression. Collectively, these data delineate an important role for NR4A2 in modulating IL-8 expression and reveal novel transcriptional responses to TNF-alpha in human inflammatory joint disease.

  19. Association of neuropeptide Y (NPY, interleukin-1B (IL1B genetic variants and correlation of IL1B transcript levels with vitiligo susceptibility.

    Directory of Open Access Journals (Sweden)

    Naresh C Laddha

    Full Text Available BACKGROUND: Vitiligo is a depigmenting disorder resulting from loss of functional melanocytes in the skin. NPY plays an important role in induction of immune response by acting on a variety of immune cells. NPY synthesis and release is governed by IL1B. Moreover, genetic variability in IL1B is reported to be associated with elevated NPY levels. OBJECTIVES: Aim of the present study was to explore NPY promoter -399T/C (rs16147 and exon2 +1128T/C (rs16139 polymorphisms as well as IL1B promoter -511C/T (rs16944 polymorphism and to correlate IL1B transcript levels with vitiligo. METHODS: PCR-RFLP method was used to genotype NPY -399T/C SNP in 454 patients and 1226 controls; +1128T/C SNP in 575 patients and 1279 controls and IL1B -511C/T SNP in 448 patients and 785 controls from Gujarat. IL1B transcript levels in blood were also assessed in 105 controls and 95 patients using real-time PCR. RESULTS: Genotype and allele frequencies for NPY -399T/C, +1128T/C and IL1B -511C/T SNPs differed significantly (p<0.0001, p<0.0001; p = 0.0161, p = 0.0035 and p<0.0001, p<0.0001 between patients and controls. 'TC' haplotype containing minor alleles of NPY polymorphisms was significantly higher in patients and increased the risk of vitiligo by 2.3 fold (p<0.0001. Transcript levels of IL1B were significantly higher, in patients compared to controls (p = 0.0029, in patients with active than stable vitiligo (p = 0.015, also in female patients than male patients (p = 0.026. Genotype-phenotype correlation showed moderate association of IL1B -511C/T polymorphism with higher IL1B transcript levels. Trend analysis revealed significant difference between patients and controls for IL1B transcript levels with respect to different genotypes. CONCLUSION: Our results suggest that NPY -399T/C, +1128T/C and IL1B -511C/T polymorphisms are associated with vitiligo and IL1B -511C/T SNP influences its transcript levels leading to increased risk for vitiligo in

  20. Direct regulation of IL-2 by curcumin.

    Science.gov (United States)

    Oh, Jin-Gyo; Hwang, Da-Jeong; Heo, Tae-Hwe

    2018-01-01

    Interleukin-2 (IL-2) is a crucial growth factor for both regulatory and effector T cells. Thus, IL-2 plays a critical role in the stimulation and suppression of immune responses. Recently, anti-IL-2 antibodies (Abs) have been shown to possess strong IL-2 modulatory activities by affecting the interaction between IL-2 and IL-2 receptors. In this study, we screened an herbal library to identify a compound that regulates IL-2, which resulted in the identification of curcumin as a direct binder and inhibitor of IL-2. Curcumin is a phytochemical with well-known anti-cancer properties. In this study, curcumin mimicked or altered the binding pattern of anti-IL-2 Abs against IL-2 and remarkably inhibited the interaction of recombinant IL-2 with the IL-2 receptor α, CD25. Interestingly, curcumin neutralized the biological activities of IL-2 both in vitro and in vivo. In this report, we elucidated the unsolved mechanism of the anti-cancer effect of curcumin by identifying IL-2 as a direct molecular target. Curcumin, as a small molecule IL-2 modulator, has the potential to be used to treat IL-2 related pathologic conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Repletion of zinc in zinc-deficient cells strongly up-regulates IL-1β-induced IL-2 production in T-cells.

    Science.gov (United States)

    Daaboul, Doha; Rosenkranz, Eva; Uciechowski, Peter; Rink, Lothar

    2012-10-01

    Mild zinc deficiency in humans negatively affects IL-2 production resulting in declined percentages of cytolytic T cells and decreased NK cell lytic activity, which enhances the susceptibility to infections and malignancies. T-cell activation is critically regulated by zinc and the normal physiological zinc level in T-cells slightly lies below the optimal concentration for T-cell functions. A further reduction in zinc level leads to T-cell dysfunction and autoreactivity, whereas high zinc concentrations (100 μM) were shown to inhibit interleukin-1 (IL-1)-induced IL-1 receptor kinase (IRAK) activation. In this study, we investigated the molecular mechanism by which zinc regulates the IL-1β-induced IL-2 expression in T-cells. Zinc supplementation to zinc-deficient T-cells increased intracellular zinc levels by altering the expression of zinc transporters, particularly Zip10 and Zip12. A zinc signal was observed in the murine T-cell line EL-4 6.1 after 1 h of stimulation with IL-1β, measured by specific zinc sensors FluoZin-3 and ZinPyr-1. This signal is required for the phosphorylation of MAPK p38 and NF-κB subunit p65, which triggers the transcription of IL-2 and strongly increases its production. These results indicate that short-term zinc supplementation to zinc-deficient T-cells leads to a fast rise in zinc levels which subsequently enhance cytokine production. In conclusion, low and excessive zinc levels might be equally problematic for zinc-deficient subjects, and stabilized zinc levels seem to be essential to avoid negative concentration-dependent zinc effects on T-cell activation.

  2. Evaluating the levels of interleukin-1 family cytokines in sporadic amyotrophic lateral sclerosis.

    Science.gov (United States)

    Italiani, Paola; Carlesi, Cecilia; Giungato, Paola; Puxeddu, Ilaria; Borroni, Barbara; Bossù, Paola; Migliorini, Paola; Siciliano, Gabriele; Boraschi, Diana

    2014-05-23

    Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease leading to the death of affected individuals within years. The involvement of inflammation in the pathogenesis of neurodegenerative diseases, including ALS, is increasingly recognized but still not well understood. The aim of this study is to evaluate the levels of inflammation-related IL-1 family cytokines (IL-1β, IL-18, IL-33, IL-37) and their endogenous inhibitors (IL-1Ra, sIL-1R2, IL-18BP, sIL-1R4) in patients with sporadic ALS (sALS), METHODS: Sera were collected from 144 patients (125 patients were characterized by disease form, duration, and disability, using the revised ALS functional rating scale (ALSFRS-R) and from 40 matched controls. Cerebrospinal fluid (CSF) was collected from 54 patients with sALS and 65 patients with other non-infectious non-oncogenic diseases as controls. Cytokines and inhibitors were measured by commercial ELISA. Among the IL-1 family cytokines tested total IL-18, its endogenous inhibitor IL-18BP, and the active form of the cytokine (free IL-18) were significantly higher in the sALS sera than in controls. No correlation between these soluble mediators and different clinical forms of sALS or the clinical setting of the disease was found. IL-18BP was the only mediator detectable in the CSF of patients. Among the IL-1 family cytokines, only IL-18 correlates with this disease and may therefore have a pathological role in sALS. The increase of total IL-18 suggests the activation of IL-18-cleaving inflammasome. Whether IL-18 upregulation in circulation of sALS patients is a consequence of inflammation or one of the causes of the pathology still needs to be addressed.

  3. IL-6 Overexpression in ERG-Positive Prostate Cancer Is Mediated by Prostaglandin Receptor EP2.

    Science.gov (United States)

    Merz, Constanze; von Mässenhausen, Anne; Queisser, Angela; Vogel, Wenzel; Andrén, Ove; Kirfel, Jutta; Duensing, Stefan; Perner, Sven; Nowak, Michael

    2016-04-01

    Prostate cancer is the most diagnosed cancer in men and multiple risk factors and genetic alterations have been described. The TMPRSS2-ERG fusion event and the overexpression of the transcription factor ERG are present in approximately 50% of all prostate cancer patients, however, the clinical outcome is still controversial. Prostate tumors produce various soluble factors, including the pleiotropic cytokine IL-6, regulating cellular processes such as proliferation and metastatic segregation. Here, we used prostatectomy samples in a tissue microarray format and analyzed the co-expression and the clinicopathologic data of ERG and IL-6 using immunohistochemical double staining and correlated the read-out with clinicopathologic data. Expression of ERG and IL-6 correlated strongly in prostate tissue samples. Forced expression of ERG in prostate tumor cell lines resulted in significantly increased secretion of IL-6, whereas the down-regulation of ERG decreased IL-6 secretion. By dissecting the underlying mechanism in prostate tumor cell lines we show the ERG-mediated up-regulation of the prostanoid receptors EP2 and EP3. The prostanoid receptor EP2 was overexpressed in human prostate cancer tissue. Furthermore, the proliferation rate and IL-6 secretion in DU145 cells was reduced after treatment with EP2-receptor antagonist. Collectively, our study shows that the expression of ERG in prostate cancer is linked to the expression of IL-6 mediated by the prostanoid receptor EP2. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  4. IL23R gene confers susceptibility to ankylosing spondylitis concomitant with uveitis in a Han Chinese population.

    Directory of Open Access Journals (Sweden)

    Hongtao Dong

    Full Text Available PURPOSE: The interleukin-23 receptor (IL-23R has been shown to be associated with ankylosing spondylitis (AS in many different populations. This study examined whether IL-23R polymorphisms were associated with susceptibility to this disease in a Chinese Han population. METHODS: Three single-nucleotide polymorphisms (SNP, rs7517847, rs11209032, and rs17375018, were genotyped in 291 AS patients and 312 age-, sex-, and ethnically matched healthy controls using a polymerase chain reaction (PCR restriction fragment length polymorphism (RFLP assay. RESULTS: The genotype and allele frequencies of rs17375018, rs7517847, and rs11209032 were not different between the patients with AS and the healthy controls. On the one hand, stratification analysis indicated that the rs17375018 GG genotype and the G allele were increased in AS patients who were HLA-B27 positive (corrected p = 0.024, odds ratio [OR] 2.35, 95% CI 1.30-4.24; p c = 0.006, OR 1.98, 95% CI 1.28-3.07, respectively. On the other hand, the analysis according to clinical characteristics showed a significantly increased prevalence of the homozygous rs17375018 GG genotype and the G allele in patients with AS and uveitis compared with the controls (p c = 0.024 and p c = 0.024, respectively. In addition, haplotype analysis performed with the SHEsis platform revealed no significant difference concerning the haplotypes between AS patients and healthy controls. CONCLUSIONS: In this study, the results suggested that the rs17375018 of IL23R was positively associated with HLA-B27-positive AS and that the rs17375018 GG of IL-23R was associated with AS concomitant with uveitis. We found no evidence for an association between the other two SNPs of IL-23R and AS.

  5. IL-33 and IgE stimulate mast cell production of IL-2 and regulatory T cell expansion in allergic dermatitis.

    Science.gov (United States)

    Salamon, P; Shefler, I; Moshkovits, I; Munitz, A; Horwitz Klotzman, D; Mekori, Y A; Hershko, A Y

    2017-11-01

    We have previously shown that mast cells (MCs) suppress chronic allergic dermatitis in mice. The underlying mechanism involves MC-derived IL-2, which supports regulatory T cell (Treg) response at the site of inflammation. However, it is not clear what are the factors that drive MCs to produce IL-2. To understand the mechanisms that lead to IL-2 production from MCs in chronic allergic dermatitis. Isolated murine bone marrow-derived MCs (BMMCs) were incubated with various stimulators, and IL-2 production was assessed by RT-PCR and ELISA. The response of signalling pathways was evaluated by MAPK inhibitors and Western blot analysis. The effect of MC-IL-2 on Tregs was studied by incubation of splenic T cells with conditioned media obtained from activated BMMCs. Dermatitis was elicited by repeated exposures of mouse ears to oxazolone. MCs in mouse and human skin samples were evaluated by immunostaining. BMMCs released IL-2 in response to IL-33, and IL-2 production was further enhanced by concomitant FcεRI activation. The effect of IL-33 was mediated by activation of the MAPK family members. IL-2 in conditioned media from IL-33 and IgE-stimulated BMMCs led to considerable expansion of Tregs in vitro. IL-33 levels were elevated in oxazolone-challenged ears along with increased numbers of IL-2-expressing MCs. Human skin with chronic inflammation also contained IL-2-expressing MCs that colocalized with IL-33 staining in the dermis. IL-33, in collaboration with IgE, is critical for MC-IL-2 production in allergic skin disease, thus leading to Treg stimulation and suppression of allergic dermatitis. © 2017 John Wiley & Sons Ltd.

  6. The lysine deacetylase inhibitor givinostat inhibits ß-cell IL-1ß induced IL-1ß transcription and processing

    DEFF Research Database (Denmark)

    Dahllöf, Mattias Salling; Christensen, Dan P; Lundh, Morten

    2012-01-01

    . Further, IL-1R antagonism improves normoglycemia and ß-cell function in type 2 diabetic patients. Inhibition of lysine deacetylases (KDACi) counteracts ß-cell toxicity induced by the combination of IL-1 and IFN¿ and reduces diabetes incidence in non-obese diabetic (NOD) mice. We hypothesized that KDACi......Aims: Pro-inflammatory cytokines and chemokines, in particular IL-1ß, IFN¿, and CXCL10, contribute to ß-cell failure and loss in DM via IL-1R, IFN¿R, and TLR4 signaling. IL-1 signaling deficiency reduces diabetes incidence, islet IL-1ß secretion, and hyperglycemia in animal models of diabetes...

  7. IL-2 and IL-15 regulate CD154 expression on activated CD4 T cells

    DEFF Research Database (Denmark)

    Skov, S; Bonyhadi, M; Odum, Niels

    2000-01-01

    The cellular and humoral immune system is critically dependent upon CD40-CD154 (CD40 ligand) interactions between CD40 expressed on B cells, macrophages, and dendritic cells, and CD154 expressed primarily on CD4 T cells. Previous studies have shown that CD154 is transiently expressed on CD4 T cells...... after T cell receptor engagement in vitro. However, we found that stimulation of PBLs with maximal CD28 costimulation, using beads coupled to Abs against CD3 and CD28, led to a very prolonged expression of CD154 on CD4 cells (>4 days) that was dependent upon autocrine IL-2 production. Previously...... activated CD4 T cells could respond to IL-2, or the related cytokine IL-15, by de novo CD154 production and expression without requiring an additional signal from CD3 and CD28. These results provide evidence that CD28 costimulation of CD4 T cells, through autocrine IL-2 production, maintains high levels...

  8. Polymorphic variations in IL-1β, IL-6 and IL-10 genes, their circulating serum levels and breast cancer risk in Indian women.

    Science.gov (United States)

    Pooja, Singh; Chaudhary, Preeti; Nayak, Lakshma V; Rajender, Singh; Saini, Karan Singh; Deol, Debashish; Kumar, Sandeep; Bid, Hemant Kumar; Konwar, Rituraj

    2012-10-01

    Cytokines are known as important regulators of the entire gamut of cancer from initiation, invasion and metastasis. This fact and plethora of gene polymorphism data prompted us to investigate cytokine gene polymorphisms in breast cancer (BC) patients. Selected polymorphisms in the IL-1β [-511 T>C (rs16944) and +3954 C>T (rs1143634)]; IL-6 [-174 G>C (rs1800795)]; IL-10 [-1082 A>G (rs1800896), -819 T>C (rs1800871) and -592 A>C (rs1800872)] genes were genotyped in 200 BC patients and 200 healthy volunteers in a case-control study using PCR-RFLP and direct DNA sequencing techniques. Peripheral cytokine levels were measured using ELISA. Allele and genotype data were analyzed for significance of differences between cases and controls using Chi-Square [χ(2)] test. Two sided P-values of less than 0.05 were considered to be statistically significant. Peripheral level of all three cytokines did not show any significant difference between cases and controls. Allele and genotype frequency of IL-1β [-511 T>C (rs16944)] did not show any difference between cases and controls. On the other hand mutant allele and genotype at IL-1β [+3954 C>T (rs1143634)] associated with increased risk of BC. This was also true for pre-menopausal cases and for mutant genotype in post-menopausal cases. Mutant allele and genotypes at IL-6 [-174 G>C (rs1800795)] appeared to be protective in nature such that controls had a higher frequency of both mutant alleles and genotypes. None of the three SNPs in IL-10 gene associated with risk of BC, except significant association of mutant allele and genotypes of -1082 A>G (rs1800896) polymorphism with postmenopausal BC. Mutant allele and genotype at IL-1β [+3954 C>T (rs1143634)] site associated with increased BC risk, while mutant allele and genotypes at IL-6 [-174 G>C (rs1800795)] polymorphism appeared to be protective. Also, there was significant association of mutant allele and genotypes of IL-10 [-1082 A>G (rs1800896)] with postmenopausal BC. None of

  9. Activation of JAK3, but not JAK1, is critical to interleukin-4 (IL4) stimulated proliferation and requires a membrane-proximal region of IL4 receptor alpha.

    Science.gov (United States)

    Malabarba, M G; Kirken, R A; Rui, H; Koettnitz, K; Kawamura, M; O'Shea, J J; Kalthoff, F S; Farrar, W L

    1995-04-21

    The tyrosine kinases JAK1 and JAK3 have been shown to undergo tyrosine phosphorylation in response to interleukin-2 (IL), IL4, IL7, and IL9, cytokines which share the common IL2 receptor gamma-chain (IL2R gamma), and evidence has been found for a preferential coupling of JAK3 to IL2R gamma and JAK1 to IL2R beta. Here we show, using human premyeloid TF-1 cells, that IL4 stimulates JAK3 to a larger extent than JAK1, based upon three different evaluation criteria. These include a more vigorous tyrosine phosphorylation of JAK3 as measured by anti-phosphotyrosine immunoblotting, a more marked activation of JAK3 as determined by in vitro tyrosine kinase assays and a more manifest presence of JAK3 in activated IL4-receptor complexes. These observations suggest that IL4 receptor signal transduction does not depend on equimolar heterodimerization of JAK1 and JAK3 following IL4-induced heterodimerization of IL4R alpha and IL2R gamma. Indeed, when human IL4R alpha was stably expressed in mouse BA/F3 cells, robust IL4-induced proliferation and JAK3 activation occurred without detectable involvement of JAK1, JAK2, or TYK2. The present study suggests that JAK1 plays a subordinate role in IL4 receptor signaling, and that in certain cells exclusive JAK3 activation may mediate IL4-induced cell growth. Moreover, mutational analysis of human IL4R alpha showed that a membrane-proximal cytoplasmic region was critical for JAK3 activation, while the I4R motif was not, which is compatible with a role of JAK3 upstream of the recruitment of the insulin receptor substrate-1/4PS signaling proteins by IL4 receptors.

  10. Effects of different types of anaesthesia (regional vs general) on serum IL-6, IL-8 and M-CSF levels in surgical patients

    International Nuclear Information System (INIS)

    Xiao Jiawang

    2009-01-01

    Objective: To study the effect of anesthesia(regional vs general) on serum IL-6, IL-8 and M-CSF levels in surgical patients. Methods: Serum IL-6, IL-8 and M-CSF levels were determined with RIA 3 times in 34 patients operated under ragional anesthesia and 34 patients operted under general anesthesia (both for benign gastral ulcer). The levels were measured before induction of anesthesia, at beginning of operation and 1 hr later. Results: In patients under regional anesthesia, the IL-6, IL-8 and M-CSF levels increased significantly at the beginning of operation and 1 hr later. Though dropped remained significantly higher than the levels before induction (P<0.05); No significant change of the levels were obsorved in patients under general anesthesia through the operation, and the levels were as a whole significantly lower than the levels under regional anesthesia (P<0.05). Conclusion: General anesthesia (combined intravenous and inhalation) could abolish increases of serum IL-6, IL-8 and M-CSF levels during operation must be of clinical values. (authors)

  11. Trichomonas vaginalis α-Actinin 2 Modulates Host Immune Responses by Inducing Tolerogenic Dendritic Cells via IL-10 Production from Regulatory T Cells.

    Science.gov (United States)

    Lee, Hye-Yeon; Kim, Juri; Ryu, Jae-Sook; Park, Soon-Jung

    2017-08-01

    Trichomonas vaginalis is a pathogen that triggers severe immune responses in hosts. T. vaginalis α-actinin 2, Tvα-actinin 2, has been used to diagnose trichomoniasis. This study was undertaken to examine the role of Tvα-actinin 2 as an antigenic molecule to induce immune responses from humans. Western blot analysis using anti-Tvα-actinin 2 antibodies indicated its presence in the secreted proteins of T. vaginalis. ELISA was employed to measure cytokine production by vaginal epithelial cells, prostate cells, mouse dendritic cells (DCs), or T cells stimulated with T. vaginalis or Tvα-actinin 2 protein. Both T. vaginalis and rTvα-actinin 2 induced cytokine production from epithelial cell lines, including IL-10. Moreover, CD4+CD25- regulatory T cells (Treg cells) incubated with rTvα-actinin 2-treated DCs produced high levels of IL-10. These data indicate that Tvα-actinin 2 modulates immune responses via IL-10 production by Treg cells.

  12. Mechanical and IL-1β Responsive miR-365 Contributes to Osteoarthritis Development by Targeting Histone Deacetylase 4

    Directory of Open Access Journals (Sweden)

    Xu Yang

    2016-03-01

    Full Text Available Mechanical stress plays an important role in the initiation and progression of osteoarthritis. Studies show that excessive mechanical stress can directly damage the cartilage extracellular matrix and shift the balance in chondrocytes to favor catabolic activity over anabolism. However, the underlying mechanism remains unknown. MicroRNAs (miRNAs are emerging as important regulators in osteoarthritis pathogenesis. We have found that mechanical loading up-regulated microRNA miR-365 in growth plate chondrocytes, which promotes chondrocyte differentiation. Here, we explored the role of the mechanical responsive microRNA miR-365 in pathogenesis of osteoarthritis (OA. We found that miR-365 was up-regulated by cyclic loading and IL-1β stimulation in articular chondrocytes through a mechanism that involved the transcription factor NF-κB. miR-365 expressed significant higher level in rat anterior cruciate ligament (ACL surgery induced OA cartilage as well as human OA cartilage from primary OA patients and traumatic OA Patients. Overexpression of miR-365 in chondrocytes increases gene expression of matrix degrading enzyme matrix metallopeptidase 13 (MMP13 and collagen type X (Col X. The increase in miR-365 expression in OA cartilage and in response to IL-1 may contribute to the abnormal gene expression pattern characteristic of OA. Inhibition of miR-365 down-regulated IL-1β induced MMP13 and Col X gene expression. We further showed histone deacetylase 4 (HDAC4 is a direct target of miR-365, which mediates mechanical stress and inflammation in OA pathogenesis. Thus, miR-365 is a critical regulator of mechanical stress and pro-inflammatory responses, which contributes cartilage catabolism. Manipulation of the expression of miR-365 in articular chondrocytes by miR-365 inhibitor may be a potent therapeutic target for the prevention and treatment of osteoarthritis.

  13. Promoter Variation and Expression Levels of Inflammatory Genes IL1A, IL1B, IL6 and TNF in Blood of Spinocerebellar Ataxia Type 3 (SCA3) Patients.

    Science.gov (United States)

    Raposo, Mafalda; Bettencourt, Conceição; Ramos, Amanda; Kazachkova, Nadiya; Vasconcelos, João; Kay, Teresa; Bruges-Armas, Jácome; Lima, Manuela

    2017-03-01

    Age at onset in spinocerebellar ataxia type 3 (SCA3/MJD) is incompletely explained by the size of the CAG tract at the ATXN3 gene, implying the existence of genetic modifiers. A role of inflammation in SCA3 has been postulated, involving altered cytokines levels; promoter variants leading to alterations in cytokines expression could influence onset. Using blood from 86 SCA3 patients and 106 controls, this work aimed to analyse promoter variation of four cytokines (IL1A, IL1B, IL6 and TNF) and to investigate the association between variants detected and their transcript levels, evaluated by quantitative PCR. Moreover, the effect of APOE isoforms, known to modulate cytokines, was investigated. Correlations between cytokine variants and onset were tested; the cumulative modifier effects of cytokines and APOE were analysed. Patients carrying the IL6*C allele had a significant earlier onset (4 years in average) than patients carrying the G allele, in agreement with lower mRNA levels produced by IL6*C carriers. The presence of APOE*ɛ2 allele seems to anticipate onset in average 10 years in patients carrying the IL6*C allele; a larger number of patients will be needed to confirm this result. These results highlight the pertinence of conducting further research on the role of cytokines as SCA3 modulators, pointing to the presence of shared mechanisms involving IL6 and APOE.

  14. Sinomenine inhibits breast cancer cell invasion and migration by suppressing NF-κB activation mediated by IL-4/miR-324-5p/CUEDC2 axis

    Energy Technology Data Exchange (ETDEWEB)

    Song, Lingqin, E-mail: qinlingsongxa@163.com [Department of Oncology, The Second Affiliated Hospital, Medical School of Xi' an Jiaotong University, Xi' an 710004 (China); Liu, Di; Zhao, Yang [Department of Oncology, The Second Affiliated Hospital, Medical School of Xi' an Jiaotong University, Xi' an 710004 (China); He, Jianjun [Department of Surgical Oncology, The First Affiliated Hospital, Medical School of Xi' an Jiaotong University, Xi' an 710061 (China); Kang, Huafeng; Dai, Zhijun; Wang, Xijing; Zhang, Shuqun; Zan, Ying [Department of Oncology, The Second Affiliated Hospital, Medical School of Xi' an Jiaotong University, Xi' an 710004 (China)

    2015-08-28

    Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a vital transcription factor that regulates multiple important biological processes, including the epithelial–mesenchymal transition (EMT) and metastasis of breast cancer. Sinomenine is an isoquinoline well known for its remarkable curative effect on rheumatic and arthritic diseases and can induce apoptosis of several cancer cell types. Recently, sinomenine was reported as a tumor suppressor via inhibiting cell proliferation and inducing apoptosis. However, the role and mechanism of sinomenine in invasion and metastasis of breast cancer are largely unknown. Here, we report that sinomenine suppressed the invasion and migration of MDA-MB-231 and 4T1 breast cancer cells in a dose-dependent manner. We detected binding of NF-κB to the inhibitor of NF-κB (IκB) after the MDA-MB-231 cells were treated with 0.25, 0.5, and 1 mM sinomenine. Co-IP analysis revealed that sinomenine enhanced the binding of NF-κB and IκB in a dose-dependent manner, suggesting that sinomenine had an effect on inactivation of NF-κB. Western blotting and ELISA approaches indicated that the suppression effect was closely associated with the phosphorylation of IκB kinase (IKK) and its negative regulator CUEDC2. Sinomenine treatment decreased miR-324-5p expression, thus increased the level of its target gene CUEDC2, and then blocked the phosphorylation of IKK through altering the upstream axis. Finally, transfection of a miR-324-5p mimic inhibited the suppression of invasion and metastasis of MDA-MB-231 and 4T1 cell by sinomenine, providing evidence that sinomenine treatment suppressed breast cancer cell invasion and metastasis via regulation of the IL4/miR-324-5p/CUEDC2 axis. Our findings reveal a novel mechanism by which sinomenine suppresses cancer cell invasion and metastasis, i.e., blocking NF-κB activation. - Highlights: • Sinomenine reduced invasion and migration of MDA-MB-231 and 4T1 breast cancer cells.

  15. Sinomenine inhibits breast cancer cell invasion and migration by suppressing NF-κB activation mediated by IL-4/miR-324-5p/CUEDC2 axis

    International Nuclear Information System (INIS)

    Song, Lingqin; Liu, Di; Zhao, Yang; He, Jianjun; Kang, Huafeng; Dai, Zhijun; Wang, Xijing; Zhang, Shuqun; Zan, Ying

    2015-01-01

    Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a vital transcription factor that regulates multiple important biological processes, including the epithelial–mesenchymal transition (EMT) and metastasis of breast cancer. Sinomenine is an isoquinoline well known for its remarkable curative effect on rheumatic and arthritic diseases and can induce apoptosis of several cancer cell types. Recently, sinomenine was reported as a tumor suppressor via inhibiting cell proliferation and inducing apoptosis. However, the role and mechanism of sinomenine in invasion and metastasis of breast cancer are largely unknown. Here, we report that sinomenine suppressed the invasion and migration of MDA-MB-231 and 4T1 breast cancer cells in a dose-dependent manner. We detected binding of NF-κB to the inhibitor of NF-κB (IκB) after the MDA-MB-231 cells were treated with 0.25, 0.5, and 1 mM sinomenine. Co-IP analysis revealed that sinomenine enhanced the binding of NF-κB and IκB in a dose-dependent manner, suggesting that sinomenine had an effect on inactivation of NF-κB. Western blotting and ELISA approaches indicated that the suppression effect was closely associated with the phosphorylation of IκB kinase (IKK) and its negative regulator CUEDC2. Sinomenine treatment decreased miR-324-5p expression, thus increased the level of its target gene CUEDC2, and then blocked the phosphorylation of IKK through altering the upstream axis. Finally, transfection of a miR-324-5p mimic inhibited the suppression of invasion and metastasis of MDA-MB-231 and 4T1 cell by sinomenine, providing evidence that sinomenine treatment suppressed breast cancer cell invasion and metastasis via regulation of the IL4/miR-324-5p/CUEDC2 axis. Our findings reveal a novel mechanism by which sinomenine suppresses cancer cell invasion and metastasis, i.e., blocking NF-κB activation. - Highlights: • Sinomenine reduced invasion and migration of MDA-MB-231 and 4T1 breast cancer cells.

  16. Polarized Th2 like cells, in the absence of Th0 cells, are responsible for lymphocyte produced IL-4 in high IgE-producer schistosomiasis patients

    Directory of Open Access Journals (Sweden)

    Soares-Silveira Alda

    2002-07-01

    Full Text Available Abstract Background Human resistance to re-infection with S. mansoni is correlated with high levels of anti-soluble adult worm antigens (SWAP IgE. Although it has been shown that IL-4 and IL-5 are crucial in establishing IgE responses in vitro, the active in vivo production of these cytokines by T cells, and the degree of polarization of Th2 vs. Th0 in human schistosomiasis is not known. To address this question, we determined the frequency of IL-4 and IFN-γ or IL-5 and IL-2 producing lymphocytes from schistosomiasis patients with high or low levels of IgE anti-SWAP. Results Our analysis showed that high and low IgE-producers responded equally to schistosomiasis antigens as determined by proliferation. Moreover, patients from both groups displayed similar percentages of circulating lymphocytes. However, high IgE-producers had an increased percentage of activated CD4+ T cells as compared to the low IgE-producers. Moreover, intracellular cytokine analysis, after short-term stimulation with anti-CD3/CD28 mAbs, showed that IgE high-producers display an increase in the percentage of T lymphocytes expressing IL-4 and IL-5 as compared to IgE low-responders. A coordinate control of the frequency of IL-4 and IL-5 producing lymphocytes in IgE high, but not IgE low-responders, was observed. Conclusions High IgE phenotype human schistosomiasis patients exhibit a coordinate regulation of IL-4 and IL-5 producing cells and the lymphocyte derived IL-4 comes from true polarized Th2 like cells, in the absence of measurable Th0 cells as measured by co-production of IL-4 and IFN-γ.

  17. Antitumor activity of IL-2/anti-IL-2 mAb immunocomplexes exerts synergism with that of N-(2-hydroxypropyl)methacrylamide copolymer-bound doxorubicin conjugate due to its low immunosuppressive activity

    Czech Academy of Sciences Publication Activity Database

    Tomala, Jakub; Chmelová, Helena; Strohalm, Jiří; Ulbrich, Karel; Šírová, Milada; Říhová, Blanka; Kovář, Marek

    2011-01-01

    Roč. 129, č. 8 (2011), s. 2002-2012 ISSN 0020-7136 R&D Projects: GA AV ČR IAA500200712; GA ČR GD310/08/H077; GA ČR GP301/07/P192; GA MŠk 1M0505 Institutional research plan: CEZ:AV0Z50200510; CEZ:AV0Z40500505 Keywords : IL-2 immunocomplexes * NK cells * HPMA copolymer-bound doxorubicin Subject RIV: EC - Immunology Impact factor: 5.444, year: 2011

  18. [Serum leptin levels and soluble leptin receptors in female patients with anorexia nervosa].

    Science.gov (United States)

    Jiskra, J; Haluzík, M; Svobodová, J; Haluzíková, D; Nedvídková, J; Parízková, J; Kotrlíková, E

    2000-10-25

    Leptin action in peripheral tissues is enabled by an interaction with specific transmembrane receptors. Several of leptin receptor isoforms were identified, including soluble leptin receptor isoform structurally identical to extracellular domain of the the long leptin receptor isoform. The soluble receptor isoform is released to the circulation and acts probably as leptin-binding factor. The aim of our study was to measure serum concentrations of the soluble leptin receptor in patients with anorexia nervosa and in the control group of healthy women. Relationships of soluble leptin receptor levels to body mass index (BMI), body fat content, serum leptin, TNF-alpha and insulin levels were also studied. 16 patients with anorexia nervosa and 16 age-matched lean healthy women were included into the study. All of the subjects were measured and weighed, the body fat content was estimated from the skinfold thickness measurement. The blood for the determination of leptin, soluble leptin receptor and other hormonal parameters was obtained from all subjects after the overnight fasting. BMI, body fat content, serum leptin and insulin levels in patients with anorexia nervosa were significantly lower than in the control group (BMI: 14.98 +/- 2.32 vs. 22.21 +/- 2.48, p anorexia nervosa were significantly higher compared the to control group (24.67 +/- 8.3 U.ml-1 vs. 15.71 +/- 2.79 U.ml-1, p anorexia nervosa were significantly higher in comparison with the healthy subjects. Except of the negative correlation between serum soluble leptin receptor levels and BMI no statistically significant relationships between serum soluble leptin receptor and the rest of parameters studied were found.

  19. IFN-γ, IL-2, IP-10, and MIG as Biomarkers of Exposure to Leishmania spp., and of Cure in Human Visceral Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Ana V. Ibarra-Meneses

    2017-05-01

    Full Text Available New biomarkers are needed for monitoring the effectiveness of treatment for visceral leishmaniasis (VL. They might also improve the detection of the asymptomatic population in Leishmania-endemic areas. This paper examines the IL-2, IFN-γ, IFN-γ-induced protein 10 (IP-10, and monokine-induced-by-IFN-γ (MIG levels in whole blood—stimulated in vitro with soluble Leishmania antigen (SLA—taken from asymptomatic individuals and patients treated for VL living in a post-outbreak (Leishmania infantum area in Spain, and in an endemic (Leishmania donovani area of Bangladesh. IP-10 was found to be an accurate global marker of asymptomatic subjects with positive cellular/humoral tests, while MIG was found to be a better marker of contact with L. donovani than IL-2 but no for those with L. infantum. Determining IP-10, MIG, and IFN-γ levels proved useful in monitoring the cellular immune response following treatment for active disease caused by L. infantum.

  20. Cytokine-like factor-1, a novel soluble protein, shares homology with members of the cytokine type I receptor family.

    Science.gov (United States)

    Elson, G C; Graber, P; Losberger, C; Herren, S; Gretener, D; Menoud, L N; Wells, T N; Kosco-Vilbois, M H; Gauchat, J F

    1998-08-01

    In this report we describe the identification, cloning, and expression pattern of human cytokine-like factor 1 (hCLF-1) and the identification and cloning of its murine homologue. They were identified from expressed sequence tags using amino acid sequences from conserved regions of the cytokine type I receptor family. Human CLF-1 and murine CLF-1 shared 96% amino acid identity and significant homology with many cytokine type I receptors. CLF-1 is a secreted protein, suggesting that it is either a soluble subunit within a cytokine receptor complex, like the soluble form of the IL-6R alpha-chain, or a subunit of a multimeric cytokine, e.g., IL-12 p40. The highest levels of hCLF-1 mRNA were observed in lymph node, spleen, thymus, appendix, placenta, stomach, bone marrow, and fetal lung, with constitutive expression of CLF-1 mRNA detected in a human kidney fibroblastic cell line. In fibroblast primary cell cultures, CLF-1 mRNA was up-regulated by TNF-alpha, IL-6, and IFN-gamma. Western blot analysis of recombinant forms of hCLF-1 showed that the protein has the tendency to form covalently linked di- and tetramers. These results suggest that CLF-1 is a novel soluble cytokine receptor subunit or part of a novel cytokine complex, possibly playing a regulatory role in the immune system and during fetal development.

  1. Immunological monitoring after organ transplantation: potential role of soluble CD30 blood level measurement.

    Science.gov (United States)

    Truong, Dinh Quang; Darwish, Ahmed A; Gras, Jérémie; Wieërs, Grégoire; Cornet, Anne; Robert, Annie; Mourad, Michel; Malaise, Jacques; de Ville de Goyet, Jean; Reding, Raymond; Latinne, Dominique

    2007-06-01

    Analysing the relevance of soluble CD30 (sCD30) in the bloodstream before and after transplantation may be important for the monitoring of transplant recipients. In this study, 27 patients (15 pediatric liver and 12 adult kidney graft recipients) were investigated. In the liver graft group, the patients who developed acute rejection during the first month (n=9) had a slightly higher sCD30 value on pre-transplantation baseline (day 0) and post-transplantation day 7, when compared to patients with normal graft function (n=6) (day 0: 102(1.6) U/ml versus 118(1.5) U/ml, p=0.52) and (day 7: 69(1.5) U/ml versus 83(1.6) U/ml, p=0.47). Increased serum sCD30 was shown to correlate with increased interleukin-10 circulating levels between day 0 and day 7 (r=0.53; p=0.04), whereas, no correlation could be evidenced between interferon-gamma (IFN-gamma) and sCD30 (r=0.02; p=0.47). Similarly, in the kidney transplantation group, no significant difference was found in sCD30 levels at day 0 in both groups with graft rejection or normal graft function (n=6) (85(1.3) U/ml versus 77(1.6) U/ml, p=0.66), but sCD30 decreased significantly at day 7 post-transplantation from baseline value in the rejection group (n=6) (77(1.6) versus 35(1.4); p=0.02). We conclude that increased serum sCD30 was correlated with increased IL-10 (interleukin-10) circulating levels, but not with IFN-gamma levels in the post-transplantation period. Neither pre-transplantation sCD30 nor sCD30 at day 7 post-transplantation could be correlated with acute rejection in liver graft recipient. The monitoring of sCD30 might constitute a tool to assess the risk of acute rejection in renal transplant but did not appear as a valuable mean for early immunological monitoring in the small group of liver allograft recipients patients analysed in this study.

  2. IL-17 Induction by ArtinM is Due to Stimulation of IL-23 and IL-1 Release and/or Interaction with CD3 in CD4+ T Cells.

    Science.gov (United States)

    da Silva, Thiago Aparecido; Mariano, Vania Sammartino; Sardinha-Silva, Aline; de Souza, Maria Aparecida; Mineo, Tiago Wilson Patriarca; Roque-Barreira, Maria Cristina

    2016-01-01

    ArtinM is a D-mannose-binding lectin extracted from the seeds of Artocarpus heterophyllus that interacts with TLR2 N-glycans and activates antigen-presenting cells (APCs), as manifested by IL-12 production. In vivo ArtinM administration induces Th1 immunity and confers protection against infection with several intracellular pathogens. In the murine model of Candida albicans infection, it was verified that, in addition to Th1, ArtinM induces Th17 immunity manifested by high IL-17 levels in the treated animals. Herein, we investigated the mechanisms accounting for the ArtinM-induced IL-17 production. We found that ArtinM stimulates the IL-17 production by spleen cells in BALB/c or C57BL/6 mice, a response that was significantly reduced in the absence of IL-23, MyD88, or IL-1R. Furthermore, we showed that ArtinM directly induced the IL-23 mRNA expression and the IL-1 production by macrophages. Consistently, in cell suspensions depleted of macrophages, the IL-17 production stimulated by ArtinM was reduced by 53% and the exogenous IL-23 acted synergistically with ArtinM in promoting IL-17 production by spleen cell suspensions. We verified that the absence of IL-23, IL-1R, or MyD88 inhibited, but did not block, the IL-17 production by ArtinM-stimulated spleen cells. Therefore, we investigated whether ArtinM exerts a direct effect on CD4+ T cells in promoting IL-17 production. Indeed, spleen cell suspensions depleted of CD4+ T cells responded to ArtinM with very low levels of IL-17 release. Likewise, isolated CD4+ T cells under ArtinM stimulus augmented the expression of TGF-β mRNA and released high levels of IL-17. Considering the observed synergism between IL-23 and ArtinM, we used cells from IL-23 KO mice to assess the direct effect of lectin on CD4+ T cells. We verified that ArtinM increased the IL-17 production significantly, a response that was inhibited when the CD4+ T cells were pre-incubated with anti-CD3 antibody. In conclusion, ArtinM stimulates the production

  3. IL-17 Induction by ArtinM is Due to Stimulation of IL-23 and IL-1 Release and/or Interaction with CD3 in CD4+ T Cells.

    Directory of Open Access Journals (Sweden)

    Thiago Aparecido da Silva

    Full Text Available ArtinM is a D-mannose-binding lectin extracted from the seeds of Artocarpus heterophyllus that interacts with TLR2 N-glycans and activates antigen-presenting cells (APCs, as manifested by IL-12 production. In vivo ArtinM administration induces Th1 immunity and confers protection against infection with several intracellular pathogens. In the murine model of Candida albicans infection, it was verified that, in addition to Th1, ArtinM induces Th17 immunity manifested by high IL-17 levels in the treated animals. Herein, we investigated the mechanisms accounting for the ArtinM-induced IL-17 production. We found that ArtinM stimulates the IL-17 production by spleen cells in BALB/c or C57BL/6 mice, a response that was significantly reduced in the absence of IL-23, MyD88, or IL-1R. Furthermore, we showed that ArtinM directly induced the IL-23 mRNA expression and the IL-1 production by macrophages. Consistently, in cell suspensions depleted of macrophages, the IL-17 production stimulated by ArtinM was reduced by 53% and the exogenous IL-23 acted synergistically with ArtinM in promoting IL-17 production by spleen cell suspensions. We verified that the absence of IL-23, IL-1R, or MyD88 inhibited, but did not block, the IL-17 production by ArtinM-stimulated spleen cells. Therefore, we investigated whether ArtinM exerts a direct effect on CD4+ T cells in promoting IL-17 production. Indeed, spleen cell suspensions depleted of CD4+ T cells responded to ArtinM with very low levels of IL-17 release. Likewise, isolated CD4+ T cells under ArtinM stimulus augmented the expression of TGF-β mRNA and released high levels of IL-17. Considering the observed synergism between IL-23 and ArtinM, we used cells from IL-23 KO mice to assess the direct effect of lectin on CD4+ T cells. We verified that ArtinM increased the IL-17 production significantly, a response that was inhibited when the CD4+ T cells were pre-incubated with anti-CD3 antibody. In conclusion, Artin

  4. Correlation of pharmacodynamic activity, pharmacokinetics, and anti-product antibody responses to anti-IL-21R antibody therapeutics following IV administration to cynomolgus monkeys

    Directory of Open Access Journals (Sweden)

    Spaulding Vikki

    2010-04-01

    Full Text Available Abstract Background Anti-IL-21R antibodies are potential therapeutics for the treatment of autoimmune diseases. This study evaluated correlations between the pharmacodynamic (PD activity, pharmacokinetics, and anti-product antibody responses of human anti-IL-21R antibodies Ab-01 and Ab-02 following IV administration to cynomolgus monkeys. Methods The PD assay was based on the ability of recombinant human IL-21 (rhuIL-21 to induce expression of the IL-2RA gene in cynomolgus monkey whole blood samples ex vivo. Monkeys screened for responsiveness to rhuIL-21 stimulation using the PD assay, were given a single 10 mg/kg IV dosage of Ab-01, Ab-02, or a control antibody (3/group, and blood samples were evaluated for PD activity (inhibition of IL-2RA expression for up to 148 days. Anti-IL-21R antibody concentrations and anti-product antibody responses were measured in serum using immunoassays and flow cytometry. Results Following IV administration of Ab-01 and Ab-02 to cynomolgus monkeys, PD activity was observed as early as 5 minutes (first time point sampled. This PD activity had good correlation with the serum concentrations and anti-product antibody responses throughout the study. The mean terminal half-life (t1/2 was ~10.6 and 2.3 days for Ab-01 and Ab-02, respectively. PD activity was lost at ~5-13 weeks for Ab-01 and at ~2 weeks for Ab-02, when serum concentrations were relatively low. The estimated minimum concentrations needed to maintain PD activity were ~4-6 nM for Ab-01 and ~2.5 nM for Ab-02, and were consistent with the respective KD values for binding to human IL-21R. For Ab-01, there was noticeable inter-animal variability in t1/2 values (~6-14 days and the resulting PD profiles, which correlated with the onset of anti-product antibody formation. While all three Ab-01-dosed animals were positive for anti-Ab-01 antibodies, only one monkey (with the shortest t1/2 and the earliest loss of PD activity had evidence of neutralizing anti-Ab-01

  5. Cord Blood Cells Responses to IL2, IL7 and IL15 Cytokines for mTOR Expression

    Directory of Open Access Journals (Sweden)

    Anahita Mohammadian

    2017-04-01

    Full Text Available Purpose: Mammalian target of rapamycin (mTORis important in hematopoiesis and affect cell growth,differentiation and survival. Although previous studies were identified the effect of cytokines on the mononuclear cells development however the cytokines effect on mTOR in cord blood mononuclear cells was unclear. The aim of this study was to evaluate mTOR expression in cord blood mononuclear and cord blood stem cells (CD34+ cells in culture conditions for lymphoid cell development. Methods: Isolation of The mononuclear cells (MNCs from umbilical cord blood were done with use of Ficollpaque density gradient. We evaluated cultured cord blood mononuclear and CD34+ cells in presece of IL2, IL7 and IL15 at distinct time points during 21 days by using flow cytometry. In this study, we presented the role of IL2, IL7 and IL15 on the expression of mTOR in cord blood cells. Results: mTOR expression were increased in peresence of IL2, IL7 and IL15 in day 14 and afterword reduced. However in persence of IL2 and IL15 expression of mTOR significantly reduced. mTOR expression in CD34+ cells decreased significantly from day7 to day 21 in culture. Conclusion: cytokines play important role in mTOR expression during hematopoiesis and development of cord blood mononuclear cells.

  6. Clinical significance of determination of changes of serum GM-CSF, IL-8, IL-6 levels after treatment in pediatric patients with bronchial asthma

    International Nuclear Information System (INIS)

    Xue Hongfeng

    2006-01-01

    Objective: To investigate the changes of serum GM-CSF, IL-8 and IL-6 levels both before and after treatment in pediatric patients with bronchial asthma. Methods: Serum GM-CSF, IL-8 and IL-6 levels were measured with RIA in 32 pediatric patients with bronchial asthma both before and after treatment as well as in 30 controls. Results: Before treatment, the serum GM-CSF, IL-8, IL-6 levels were significantly higher in the patients than those in the controls (P 0.05). Conclusion: Abnormal high serum GM-CSF, IL-8, IL-6 levels played important role in the pathogenesis of bronchial asthma in children. (authors)

  7. Study on the serum levels of relevant cytokines IL-β, IL-6, IL-8 and tumor markers CEA, CA15-3, PRL in breast cancer patients with bone metastatic lesions shown on SPECT radio-nuclide bone scan

    International Nuclear Information System (INIS)

    Zhu Bao

    2009-01-01

    Objective: To explore the correlationship between SPECT radionuclide bone scan and serum levels of three tumor markers as well as three cytokines in patients with breast cancer. Methods: Serum levels of IL-1β, IL-6, IL-8, CEA, CA15-3(with RIA) and PRL(with CLIA) were determined in 1)20 breast cancer patients with definite bone metastatic lesions shown on radio-nuclide bone scan 2) 20 breast cancer patients without bone metastasis 3) 30 patients with benign breast disorders and 4) 35 controls. Results: The serum tumor markers levels in patients osseous metastasis were significantly higher than those in the other three groups (P 0.05). The serum levels of IL-6, IL-8, IL-1β in patients with osseous metastasis were also significantly higher than those in other groups(P<0.05). Conclusion: Over expression of CEA, CA15-3 and PRL as well as IL-6, IL-8, IL-1β were related with osseous metastasis from breast cancer. Determination of the levels of these six parameters would be helpful for dynamic monitoring of the extent of metastasis. (authors)

  8. Clinical significance of determination of the levels of serum IL-6, TNF-α and hs-CRP in patients with DM2 complicated with coronary heart disease (CHD)

    International Nuclear Information System (INIS)

    Li Juan; Zhao Qian; Zhang Dajun

    2007-01-01

    Objective: To investigate the significance of changes of serum IL-6, TNF-α, hs-CRP levels in development of coronary heart disease in patients with type 2 diabetes mellitus. Methods: Serum IL-6, TNF-α (with RIA). hs-CRP (with CLIA) and FPG, TG, cholesterol (with biochemistry) contents were measured in (1) DM2 patients complicated with CHD, n=40 and (2) DlVI2 patients without CHD, n=48. Results: The BMI and FPG, TG levels were significantly higher in patients complicated with heart disease than those in patients without CHD (P<0.05) with the exception of cholesterol. The levels of IL-6, TNF-α and hs-CRP were also significantly higher in patients with heart disease than those in patients without heart disease (P<0.05). Conclusion: The high levels of IL-6, TNF-α and hs-CRP played important role in the development of coronary heart disease. Monitoring those levels might be helpful in assessment of treatment efficacy and outcome prediction. (authors)

  9. Protein kinase CK2 modulates IL-6 expression in inflammatory breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Drygin, Denis, E-mail: ddrygin@cylenepharma.com; Ho, Caroline B.; Omori, Mayuko; Bliesath, Joshua; Proffitt, Chris; Rice, Rachel; Siddiqui-Jain, Adam; O' Brien, Sean; Padgett, Claire; Lim, John K.C.; Anderes, Kenna; Rice, William G.; Ryckman, David

    2011-11-11

    Highlights: Black-Right-Pointing-Pointer We examine the potential cross-talk between CK2 and IL-6. Black-Right-Pointing-Pointer Inhibition of CK2 by siRNA or CX-4945 inhibits expression of IL-6 in models of IBC. Black-Right-Pointing-Pointer Treatment of IBC patient in the clinic with CX-4945 reduces her IL-6 plasma levels. Black-Right-Pointing-Pointer We demonstrate that CK2 is a potential therapeutic target for IL-6 driven diseases. -- Abstract: Inflammatory breast cancer is driven by pro-angiogenic and pro-inflammatory cytokines. One of them Interleukin-6 (IL-6) is implicated in cancer cell proliferation and survival, and promotes angiogenesis, inflammation and metastasis. While IL-6 has been shown to be upregulated by several oncogenes, the mechanism behind this phenomenon is not well characterized. Here we demonstrate that the pleotropic Serine/Threonine kinase CK2 is implicated in the regulation of IL-6 expression in a model of inflammatory breast cancer. We used siRNAs targeted toward CK2 and a selective small molecule inhibitor of CK2, CX-4945, to inhibit the expression and thus suppress the secretion of IL-6 in in vitro as well as in vivo models. Moreover, we report that in a clinical trial, CX-4945 was able to dramatically reduce IL-6 levels in plasma of an inflammatory breast cancer patient. Our data shed a new light on the regulation of IL-6 expression and position CX-4945 and potentially other inhibitors of CK2, for the treatment of IL-6-driven cancers and possibly other diseases where IL-6 is instrumental, including rheumatoid arthritis.

  10. The effects of IL-1β, IL-8, G-CSF and TNF-α as molecular adjuvant on the immune response to an E. tarda subunit vaccine in flounder (Paralichthys olivaceus).

    Science.gov (United States)

    Guo, Ming; Tang, Xiaoqian; Sheng, Xiuzhen; Xing, Jing; Zhan, Wenbin

    2018-06-01

    Cytokines play vital roles in mounting immune responses and activating host defense network. In this study, the expression plasmid pcDNA3.1 (pcN3) encoding four flounder (Paralichthys olivaceus) cytokines including IL-1β, TNF-α, IL-8 or G-CSF (pcIL-1β, pcTNF-α, pcIL-8 and pcG-CSF) were successfully constructed, and their adjuvant potential on an Edwardsiella tarda (E. tarda) subunit vaccine OmpV (rOmpV) were comparatively analyzed in vaccinated flounder model. Results revealed that flounder vaccinated with rOmpV plus pcIL-1β, pcIL-8 or pcG-CSF produced the relative percent survivals (RPS) of 71%, 65% and 49% respectively, which were higher than that in flounder vaccinated with rOmpV plus pcTNF-α (39%) or pcN3 (36%, the control group). Immunological analysis showed that: (1) except pcTNF-α, higher levels of anti-E. tarda serum antibodies and sIg + lymphocytes in spleen, head kidney and peripheral blood were significantly enhanced by pcIL-1β, pcIL-8 or pcG-CSF, however, pcIL-8 and pcIL-1β enhanced higher levels of sIg + lymphocytes and anti-E. tarda antibodies than pcG-CSF; (2) pcTNF-α could promote the up-regulation of genes participated in cellular immunity (MHCIα, IFN-γ, CD8α and CD8β), pcIL-1β could enhance the expression of genes related to humoral immunity (CD4-1, CD4-2, MHCIIα and IgM), and all the detected genes were augmented by pcIL-8 and pcG-CSF; Among the four cytokines, pcIL-8 and pcIL-1β could strengthen the highest levels of genes participated in cellular immunity and humoral immunity, respectively. These results demonstrated that pcIL-8 and pcIL-1β could enhance stronger cellular and/or humoral immunity induced by rOmpV than pcG-CSF and pcTNF-α, and evoked higher RPS against E. tarda challenge in flounder, which indicated that pcIL-8 and pcIL-1β are promising adjuvants of vaccines in controlling E. tarda infection. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. EVALUATION OF THE ROLE OF INTERLEUKIN-8 (IL -8), SOLUBLE INTERCELLULAR ADHESION MOLECULE-1(SICAM-1) AND EOSINOPHIL CATIONIC PROTEIN (ECP) IN PATHOGENESIS OF BRONCHIAL ASTHMA

    International Nuclear Information System (INIS)

    EL-NASHAR, N.A.; MOSTAFA, A.M.E.; AHMED, S.M.; ABDEL-LATIF, A.

    2008-01-01

    Bronchial asthma remains a leading cause of chronic illness in children. Current theories of the pathogenesis of asthma suggest that airway inflammation is an important determinant of bronchial hyperactivity .The interaction of several inflammatory cells, soluble mediators and adhesion molecules may be important determinants of asthma. Since a better understanding of the underlying mechanisms leading to asthma pathology may yield more specific immunological strategies for the treatment of this disease, this study was designed to investigate the contribution of these markers to airway inflammation. The present study included 25 children with asthma and 15 control children. The asthma cases were 18 males and 7 females ( mean age= 9.36 ± 2.16 years). According to the severity of asthma, patients were classified as mild (n=10), moderate (n=9) and severe (n=6) asthma. They were further classified into allergic asthmatics (extrinsic atopic, n=10) and non-allergic (intrinsic asthmatics, n=15). Estimations of serum levels of IL-8, sICAM-1(by ELISA) and ECP (by flouroimmunoassay) were done. The results of this study revealed that serum levels of IL-8 were significantly higher in asthmatics than in controls. Also, serum levels of it were significantly higher in cases with severe and cases with moderate asthma than in cases with mild asthma. Serum levels of sICAM-1 were significantly higher in asthmatic than in control children, in severe than in moderate, and in both than in mild asthma cases. Levels of ECP were significantly higher in asthmatics than in controls. Also, serum levels of it were related to asthma severity. Furthermore, the three biomarkers showed higher expression in allergic asthmatics versus non- allergies. There were positive correlations of IL-8, sICAM-1, ECP and IgE with each other in asthmatic children that may indicate interaction of these markers in regulation and persistence of inflammatory cascade in asthma through different mechanisms. In

  12. Clinical significance of determination of changes of serum IGF-II, IL-6, IL-8, TNF-α levels after treatment in children with bronchopneumonia

    International Nuclear Information System (INIS)

    Feng Yue

    2011-01-01

    Objective: To explore the clinical significance of changes of serum IGF-II, IL-6, IL-8 and TNF-α levels after treatment in children with bronchopneumonia. Methods: Serum IGF-II, IL-6, IL-8 and TNF-α levels with RIA were detected both before and after treatment in 33 patients with children bronchopneumonia as well as in 35 controls. Results: Before treatment, serum IGF-II, IL-6, IL-8 and TNF-α levels were significantly higher in the patients than those in the controls (P 0.05). Conclusions: Serum IGF-II, IL-6, IL-8 and TNF-α could take part in the pathogenesis of children bronchopneumonia in various ways and determination of these levels was clinically important. (authors)

  13. Clinical significance of measurement of changes of serum hs-CRP, IL-6, IL-8 M-CSF levels after treatment in patients with endometriosis

    International Nuclear Information System (INIS)

    Chen Xiaochao; Zhou Dongxia; Zhang Limin; Liu Hongshu

    2008-01-01

    Objective: To explore the significance of changes of serum hs-CRP, IL-6, IL-8 and M-CSF levels after treatment in patients with endometriosis. Methods: Serum IL-6, IL-8, M -CSF(with RIA), hs-CRP(with immuneturbidity method)levels were determined in 33 patients with endometriosis both before and after treatment as well as in 35 controls. Results: Before treatment, the serum hs-CRP, IL-6, IL-8 and M-CSF levels were significantly higher in the patients than those in controls (P 0.05). Conclusion: Detection of serum hs-CRP, IL-6, IL-8 and M-CSF levels might reflect the progress of diseases in patients with endometriosis. (authors)

  14. Elevated Levels of Cytokines Associated with Th2 and Th17 Cells in Vitreous Fluid of Proliferative Diabetic Retinopathy Patients.

    Directory of Open Access Journals (Sweden)

    Masaru Takeuchi

    Full Text Available Macrophages are involved in low-grade inflammation in diabetes, and play pathogenic roles in proliferative diabetic retinopathy (PDR by producing proinflammatory cytokines. T cells as well as other cells are also activated by proinflammatory cytokines, and infiltration into the vitreous of patients with PDR has been shown. In this study, we measured helper T (Th cell-related cytokines in the vitreous of PDR patients to define the characteristics of Th-mediated immune responses associated with PDR. The study group consisted of 25 type 2 diabetic patients (25 eyes with PDR. The control group consisted of 27 patients with epiretinal membrane (ERM, 26 patients with idiopathic macular hole (MH, and 26 patients with uveitis associated with sarcoidosis. Vitreous fluid was obtained at the beginning of vitrectomy, and centrifuging for cellular removals was not performed. Serum was also collected from PDR patients. IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, soluble sCD40L, and TNFα in the vitreous and serum samples were measured. Both percent detectable and levels of IL-4, IL-6, IL-17A, IL-21, IL-22, and TNFα in the vitreous were significantly higher than those in the serum in PDR patients. Vitreous levels of these cytokines and IL-31 were significantly higher in PDR than in ERM or MH patients. Vitreous levels of IL-4, IL-17A, IL-22, IL-31, and TNFα in PDR patients were also significantly higher than those of sarcoidosis patients. In PDR patients, vitreous IL-17A level correlated significantly with vitreous levels of IL-22 and IL-31, and especially with IL-4 and TNFα. Although it is unclear whether these cytokines play facilitative roles or inhibitory roles for the progression of PDR, the present study indicated that Th2- and Th17-related immune responses are involved in the pathogenesis of PDR.

  15. CCR3 expression induced by IL-2 and IL-4 functioning as a death receptor for B cells

    DEFF Research Database (Denmark)

    Jinquan, Tan; Jacobi, Henrik H; Jing, Chen

    2003-01-01

    We report that CCR3 is not expressed on freshly isolated peripheral and germinal B cells, but is up-regulated after stimulation with IL-2 and IL-4 (approximately 98% CCR3(+)). Ligation of CCR3 by eotaxin/chemokine ligand (CCL) 11 induces apoptosis in IL-2- and IL-4-stimulated primary CD19......-4, and eotaxin/CCL11 (88% CD95 and 84% CD95L). We therefore propose that ligation of such newly induced CCR3 on peripheral and germinal B cells by eotaxin/CCL11 leads to the enhanced levels of CD95 and CD95L expression. Ligation of CD95 by its CD95L expressed on neigboring B cells triggers relevant....... Interaction between CCR3 and eotaxin/CCL11 may, besides promoting allergic reactions, drive activated B cells to apoptosis, thereby reducing levels of Ig production, including IgE, and consequently limit the development of the humoral immune response. The apoptotic action of eotaxin/CCL11 suggests...

  16. High-level expression and purification of soluble recombinant FGF21 protein by SUMO fusion in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Huang Yadong

    2010-02-01

    Full Text Available Abstract Background Fibroblast growth factor 21 (FGF21 is a promising drug candidate to combat metabolic diseases. However, high-level expression and purification of recombinant FGF21 (rFGF21 in Escherichia coli (E. coli is difficult because rFGF21 forms inclusion bodies in the bacteria making it difficult to purify and obtain high concentrations of bioactive rFGF21. To overcome this problem, we fused the FGF21 with SUMO (Small ubiquitin-related modifier by polymerase chain reaction (PCR, and expressed the fused gene in E. coli BL21(DE3. Results By inducing with IPTG, SUMO-FGF21 was expressed at a high level. Its concentration reached 30% of total protein, and exceeded 95% of all soluble proteins. The fused protein was purified by DEAE sepharose FF and Ni-NTA affinity chromatography. Once cleaved by the SUMO protease, the purity of rFGF21 by high performance liquid chromatography (HPLC was shown to be higher than 96% with low endotoxin level (in vivo animal experiments showed that rFGF21 produced by using this method, could decrease the concentration of plasma glucose in diabetic rats by streptozotocin (STZ injection. Conclusions This study demonstrated that SUMO, when fused with FGF21, was able to promote its soluble expression of the latter in E. coli, making it more convenient to purify rFGF21 than previously. This may be a better method to produce rFGF21 for pharmaceutical research and development.

  17. Downregulation of miR-221-3p contributes to IL-1β-induced cartilage degradation by directly targeting the SDF1/CXCR4 signaling pathway.

    Science.gov (United States)

    Zheng, Xin; Zhao, Feng-Chao; Pang, Yong; Li, Dong-Ya; Yao, Sheng-Cheng; Sun, Shao-Song; Guo, Kai-Jin

    2017-06-01

    Osteoarthritis (OA) is characterized by degradation of chondrocyte extracellular matrix (ECM). Accumulating evidence suggests that microRNAs (miRNAs) are associated with OA, but little is known of their function in chondrocyte ECM degradation. The objective of this study was to investigate the expression and function of miRNAs in OA. miRNA expression profile was determined in OA cartilage tissues and controls, employing Solexa sequencing and reverse transcription quantitative PCR (RT-qPCR). According to a modified Mankin scale, cartilage degradation was evaluated. Functional analysis of the miRNAs on chondrocyte ECM degradation was performed after miRNA transfection and IL-1β treatment. Luciferase reporter assays and western blotting were employed to determine miRNA targets. Expression of miR-221-3p was downregulated in OA cartilage tissues, which was significantly correlated with a modified Mankin scale. Through gain-of-function and loss-of-function studies, miR-221-3p was shown to significantly affect matrix synthesis gene expression and chondrocyte proliferation and apoptosis. Using SW1353 and C28I2 cells, SDF1 was identified as a target of miR-221-3p. SDF1 overexpression resulted in increased expression of catabolic genes such as MMP-13 and ADAMTS-5 in response to IL-1β, but these effects were moderated by miR-221-3p. SDF1 treatment antagonized this effect, while knockdown of SDF1 by shSDF1 induced inhibitory effects on the expression of CXCR4 and its main target genes, similar to miR-221-3p. The results indicate that upregulation of miR-221-3p could prevent IL-1β-induced ECM degradation in chondrocytes. Targeting the SDF1/CXCR4 signaling pathway may be used as a therapeutic approach for OA. miR-221-3p is downregulated in human cartilage tissues. miR-221-3p levels are associated with cartilage degeneration grade. miR-221-3p upregulation prevents IL-1β-induced ECM degradation in chondrocytes. Protection of ECM degradation by miR-223-3p occurs via SDF1/CXCR4

  18. Human retinal pigment epithelial cells inhibit proliferation and IL2R expression of activated T cells

    DEFF Research Database (Denmark)

    Kaestel, Charlotte G; Jørgensen, Annette; Nielsen, Mette

    2002-01-01

    -Thymidine incorporation assay, respectively. T cells and RPE cells were cultured directly together or in a transwell system for determination of the effect of cell contact. The importance of cell surface molecules was examined by application of a panel of blocking antibodies (CD2, CD18, CD40, CD40L, CD54, CD58......) in addition to use of TCR negative T cell lines. The expression of IL2R-alpha -beta and -gamma chains of activated T cells was analysed by flow cytometry after incubation of T cells alone or with RPE cells. Human RPE cells were found to inhibit the proliferation of activated T cells by a cell contact......-beta and -gamma chain expression within 24 hr after removal from the coculture. It is concluded that the cultured human adult and foetal RPE cells inhibit the proliferation of activated T cells by a process that does not involve apoptosis. It depends on cell contact but the involved surface molecules were...

  19. Impact of genetic variants of IL-6, IL6R, LRP5, ESR1 and SP7 genes on bone mineral density in postmenopausal Mexican-Mestizo women with obesity.

    Science.gov (United States)

    Méndez, Juan Pablo; Rojano-Mejía, David; Coral-Vázquez, Ramón Mauricio; Coronel, Agustín; Pedraza, Javier; Casas, María José; Soriano, Ruth; García-García, Eduardo; Vilchis, Felipe; Canto, Patricia

    2013-10-10

    Since obesity and osteoporosis present a high genetic predisposition and polymorphisms of IL-6, IL6R, LRP5, ESR1 and SP7 may influence the risk of both diseases, the aim of this study was to analyze the possible association of polymorphisms in these genes, as well as their haplotypes, with BMD variations in postmenopausal Mexican-Mestizo women with grade 2 or grade 3 obesity. One hundred eighty unrelated postmenopausal women with grade 2 or grade 3 obesity were included. BMD was measured in total hip and lumbar spine by dual-energy X-ray absorptiometry. DNA was obtained from blood leukocytes. Rs1800795 of IL-6, rs2228145 of IL6R, rs3736228 of LRP5, rs9340799 (XbaI) and rs2234693 (PvuII), of ESR1, rs10876432 and rs2016266, of SP7 (and their haplotypes), were studied by real-time PCR allelic discrimination. Deviations from Hardy-Weinberg equilibrium were tested. Pairwise linkage disequilibrium between single nucleotide polymorphisms was calculated by direct correlation r(2), and haplotype analysis was conducted. Using WHO criteria, 54.5% had grade 2 obesity, and 45.5% had grade 3 obesity. Regarding DXA results, 11.1% women had osteoporosis, 41.7% had osteopenia, and 47.2% had normal BMD. Genotype and haplotype analysis showed no significant differences with BMD variations at the lumbar spine, total hip or femoral neck. We did not find a significant association between the polymorphisms analyzed or their haplotypes and BMD variations in postmenopausal women with obesity. The higher BMD observed in women with obesity could be the result of an adaptive response to the higher loading of the skeleton. © 2013 Elsevier B.V. All rights reserved.

  20. A Brief History of IL-1 and IL-1 Ra in Rheumatology

    Directory of Open Access Journals (Sweden)

    Jean-Michel Dayer

    2017-05-01

    Full Text Available The history of what, in 1979, was called interleukin-1 (IL-1, orchestrator of leukocyte inter-communication, began many years before then, initially by the observation of fever induction via the endogenous pyrogen (EP (1974 and then in rheumatology on the role in tissue destruction in rheumatoid diseases via the induction of collagenase and PGE2 in human synovial cells by a mononuclear cell factor (MCF (1977. Since then, the family has exploded to presently 11 members as well as many membrane-bound and soluble receptor forms. The discovery of a natural Interleukin-1 receptor antagonist (IL-1Ra in human biological fluids has highlighted the importance of IL-1 and IL-1Ra in human diseases. Evidence delineating its role in autoinflammatory syndromes and the elucidation of the macromolecular complex referred to as “inflammasome” have been instrumental to our understanding of the link with IL-1. At present, the IL-1blockade as therapeutic approach is crucial for many hereditary autoinflammatory diseases, as well as for adult-onset Still’s disease, crystal-induced arthropathies, certain skin diseases including neutrophil-triggered skin diseases, Behçet’s disease and deficiency of IL-1Ra and other rare fever syndromes. Its role is only marginally important in rheumatoid arthritis and is still under debate with regard to osteoarthritis, type 2 diabetes mellitus, cardiovascular diseases and cancer. This brief historical review focuses on some aspects of IL-1, mainly IL-1β and IL-Ra, in rheumatology. There are many excellent reviews focusing on the IL-1 family in general or with regard to specific diseases or biological discoveries.

  1. Clinical significance of determination of changes of serum IL-6, IL-10 and GM-CSF levels after treatment in pediatric patients with bronchial asthma

    International Nuclear Information System (INIS)

    Qin Wenjing

    2008-01-01

    Objective: To explore the changes of Serum IL-6, IL-10 and GM-CSF levels after treatment in pediatric patients with bronchial asthma. Methods: Serum IL-6, IL-10 and GM-CSF levels were measured with RIA in 33 pediatric patients with bronchial asthma both before and after treatment as well as in 30 controls. Results: Before treatment, the serum IL-6, IL-10 and GM-CSF levels were significantly higher than those in controls (P 0.05). Conclusion: Detection of serum IL-6, IL-10 and GM-CSF levels were useful for assessment of therapeutic efficacy and were of important clinical values in pediatric patients with bronchial asthma. (authors)

  2. Estimation by limiting dilution analysis of human IL 2-secreting T cells: detection of IL 2 produced by single lymphokine-secreting T cells

    International Nuclear Information System (INIS)

    Vie, H.; Miller, R.A.

    1986-01-01

    We present here a culture method for the estimation, in human blood, of the number of lymphocytes that can respond to mitogen by producing interleukin 2 (IL 2). T cells are cultured at limiting dilutions with PHA or Con A in the presence of Epstein Barr virus-transformed human lymphoblastoid cells (EB-LCL), and supernatants are tested 3 days later for IL 2 content by a cell proliferation assay. The distribution of negative wells follows the expected Poisson single-hit relationship, suggesting that the assay is sensitive to single cells of a single limiting cell type. On average, 16.3% of peripheral blood mononuclear cells can produce IL 2 in such clonal cultures (mean of 12 determinations; SD = 5.6%). Surprisingly, irradiation (up to 2000 rad) of the titrated responder cell population diminishes the estimated frequencies by less than 50%. The ability to detect IL 2 levels in cultures containing only a single, nonproliferating T lymphocyte allows us to estimate the amount of IL 2 generated by an individual effector cell during a 3-day culture interval after mitogen stimulation. The average responding, irradiated T cell generates 0.92 pg of IL 2 (median) within 3 days. The method presented provides a straightforward way to provide independent estimates of responding cell number and of lymphokine production per cell in a variety of clinical situations

  3. Pregnancy, but not the allergic status, influences spontaneous and induced interleukin-1beta (IL-1beta), IL-6, IL-10 and IL-12 responses.

    Science.gov (United States)

    Amoudruz, Petra; Minang, Jacob Taku; Sundström, Yvonne; Nilsson, Caroline; Lilja, Gunnar; Troye-Blomberg, Marita; Sverremark-Ekström, Eva

    2006-09-01

    In this study, we investigated how pregnancy influences cytokine production in response to stimulation of the innate and the adaptive immune system, respectively. Peripheral blood mononuclear cells (PBMCs) from allergic (n = 44) and non-allergic (n = 36) women were collected at three time-points: during the third trimester, at delivery and at a non-pregnant state 2 years after delivery. The production of interleukin-1beta (IL-1beta), IL-6, IL-10 and IL-12 was measured by enzyme-linked immunosorbent assay (ELISA) or enzyme-linked immunospot assay (ELISPOT). The spontaneous cytokine production, and the response following stimulation with agents that primarily activate the adaptive part of the immune system [phytohaemagglutinin (PHA), allergen extracts from cat and birch], or lipopolysaccharide (LPS) that activate innate immunity was measured in vitro. There was a significantly higher spontaneous in vitro production of IL-1beta, IL-6 and IL-10 by PBMCs during pregnancy than 2 years after pregnancy, and this was not affected by the allergic status of the women. Conversely, in PHA-stimulated cell cultures there was a lower production of IL-10 and IL-12 during pregnancy than 2 years after pregnancy. LPS-induced IL-6 levels were significantly lower in PBMCs obtained during pregnancy than at 2 years after pregnancy. In addition, we made the interesting observation that in allergic women total immunoglobulin E (IgE) levels were significantly lower 2 years after pregnancy compared to the levels during pregnancy. Taken together, our results indicate that while atopic allergy in women does not have a substantial effect on cytokine production, pregnancy has an obvious effect on the immune system in terms of cytokine production as well as on the total IgE levels.

  4. Involvement of IL-33 in the pathogenesis of rheumatoid arthritis: the effect of etanercept on the serum levels of IL-33.

    Science.gov (United States)

    Kageyama, Yasunori; Torikai, Eiji; Tsujimura, Kunio; Kobayashi, Masato

    2012-02-01

    To investigate the role of interleukin (IL)-33 in rheumatoid arthritis (RA) patients, we measured the serum levels of IL-33 in RA patients before and after the administration of etanercept. Twenty-four patients with RA were treated with etanercept. Clinical and laboratory examinations, including serum levels of C-reactive protein (CRP) and hemoglobin (Hb); white blood cell (WBC) and red blood cell (RBC) counts; and the Disease Activity Score of 28 joints including CRP (DAS28-CRP), were performed at the baseline and at 3 and 6 months after the initial treatment with etanercept. The mean serum IL-33 levels had decreased significantly at 3 and 6 months after the initial treatment with etanercept. Serum IL-33 levels showed a significant correlation with the number of tender joints, CRP, DAS28-CRP, and the WBC count, and an inverse correlation with the RBC count and Hb level. These findings indicated that the decrease of serum IL-33 levels was a novel function of etanercept, shown for the first time in this study. Measurement of serum levels of IL-33 may become a useful control marker for RA treatment.

  5. Interleukin-1β (IL-1β) increases pain behavior and the blood glucose level: possible involvement of sympathetic nervous system.

    Science.gov (United States)

    Sim, Yun-Beom; Park, Soo-Hyun; Kang, Yu-Jung; Jung, Jun-Sub; Ryu, Ohk-Hyun; Choi, Moon-Gi; Suh, Hong-Won

    2012-07-01

    The relationship between interleukin-1β (IL-1β)-induced nociception and the blood glucose level was studied in ICR mice. We found in the present study that intrathecal (i.t.) injection of IL-1β increased pain behavior. In addition, i.t. IL-1β injection caused an elevation of the blood glucose level. The time-course study showed that maximal blood glucose level was observed 30 and 60 min after i.t. IL-1β administration. Furthermore, i.t. injection of IL-1β enhanced the blood glucose level when mice were orally fed with d-glucose. The i.t. administration of IL-1β antagonist (AF12198) inhibited the hyperglycemia and pain behaviors induced by IL-1β. We found in the present study that adrenal tyrosine hydroxylase (TH) mRNA level was also increased by i.t. IL-1β injection. Furthermore, intraperitoneal (i.p.) pretreatment with phentolamine (an α(1)-adrenergic blocker) or yohimbine (an α(2)-adrenergic blocker) significantly attenuated the blood glucose level and pain behavior induced by IL-1β administered i.t. However, the blood glucose level and pain behavior were not affected by butoxamine (a β(2)-adrenergic blocker), whereas metoprolol (a β(2)-adrenergic blocker) enhanced IL-1β-induced blood glucose level and pain behavior in mice fed with d-glucose. However, its effect was not statistically significant. Our results suggest that IL-1β administered i.t. increases the blood glucose level via an activation of α adrenergic nervous system. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Soluble factors from biofilm of Candida albicans and Staphylococcus aureus promote cell death and inflammatory response.

    Science.gov (United States)

    de Carvalho Dias, Kassia; Barbugli, Paula Aboud; de Patto, Fernanda; Lordello, Virginia Barreto; de Aquino Penteado, Letícia; Medeiros, Alexandra Ivo; Vergani, Carlos Eduardo

    2017-06-30

    The objective of this study was to better understand the effects of soluble factors from biofilm of single- and mixed-species Candida albicans (C. albicans) and methicillin-sensitive Staphylococcus aureus (MSSA) cultures after 36 h in culture on keratinocytes (NOK-si and HaCaT) and macrophages (J774A.1). Soluble factors from biofilms of C. albicans and MSSA were collected and incubated with keratinocytes and macrophages, which were subsequently evaluated by cell viability assays (MTT). Lactate dehydrogenase (LDH) enzyme release was measured to assess cell membrane damage to keratinocytes. Cells were analysed by brightfield microscopy after 2 and 24 h of exposure to the soluble factors from biofilm. Cell death was detected by labelling apoptotic cells with annexin V and necrotic cells with propidium iodide (PI) and was visualized via fluorescence microscopy. Soluble factors from biofilm were incubated with J774A.1 cells for 24 h; the subsequent production of NO and the cytokines IL-6 and TNF-α was measured by ELISA. The cell viability assays showed that the soluble factors of single-species C. albicans cultures were as toxic as the soluble factors from biofilm of mixed cultures, whereas the soluble factors of MSSA cultures were less toxic than those of C. albicans or mixed cultures. The soluble factors from biofilm of mixed cultures were the most toxic to the NOK-si and HaCaT cells, as confirmed by analyses of PI labelling and cell morphology. Soluble factors from biofilm of single-species MSSA and mixed-species cultures induced the production of IL-6, NO and TNF-α by J744A.1 macrophages. The production of IL-6 and NO induced by the soluble factors from biofilm of mixed cultures was lower than that induced by the soluble factors from biofilm of single-species MSSA cultures, whereas the soluble factors from biofilm of C. albicans cultures induced only low levels of NO. Soluble factors from 36-h-old biofilm of C. albicans and MSSA cultures promoted cell death and

  7. Reduced IL-7R T Cell Expression and Increased Plasma sCD127 in Late Presenting HIV-Infected Individuals

    DEFF Research Database (Denmark)

    Hartling, Hans J; Jespersen, Sofie; Gaardbo, Julie C

    2017-01-01

    homeostasis. This study aimed to describe IL-7R and IL-7 before and after initiation of cART in late presenting HIV-infected individuals, and the impact on immune recovery and T cell subset distribution after initiation of cART. METHODS: A total of 100 HIV-infected individuals initiating cART were included......BACKGROUND: Late presentation of HIV infection is associated with reduced chance of optimal immune recovery after initiating combination antiretroviral therapy (cART). Interleukin-7 (IL-7) and the corresponding receptor, IL-7 receptor (IL-7R) made up of CD127 and CD132, are crucial for T cell...

  8. Influence of genetic polymorphisms of IL23R, STAT3, IL12B, and STAT4 on the risk of aplastic anemia and the effect of immunosuppressive therapy.

    Science.gov (United States)

    Zhao, Li; Zhu, Huanling; Han, Bing; Wang, Lixin; Sun, Yuming; Lu, Xiaojun; Huang, Chunyan; Tan, Bin; Chen, Chunxia; Qin, Li

    2018-04-01

    Studies have suggested that IL-23/STAT3 and IL-12/STAT4 signaling pathways associate with aplastic anemia (AA) occurrence. Polymorphisms in pathway-related genes may contribute to AA risk. In the current study, we investigated the association between polymorphisms in genes of IL23R, STAT3, IL12B, and STAT4 and occurrence, severity, and immunosuppressive outcome of AA in the Han population in southwest China. In the current 164 AA cases and 211 controls study, we found T allele and TT genotype of rs7574865 were more frequent in the cases than that in the controls. In the additive model, individual carrying rs7574865 T allele demonstrated a 37% (OR (95% CI) = 1.37 (1.02-1.85), Pper = 0.036) increased AA risk. In the recessive model, carrier with rs7574865 TT genotype showed a 2.08-fold increased AA risk (OR (95% CI) = 2.08 (1.14-3.70), Pper = 0.017). Additionally, we showed that G allele and GG genotype of rs11209032 were more frequent in the 88 non-severe AA cases than that in the 76 severe AA ones. Our study also found G allele and GG genotype of rs11209032, and GG-genotype of rs744166 associated with the immunosuppressive therapy outcome in AA patients. Current study results support that functional STAT4 (rs7574865), IL23R (rs11209032), and STAT3 (rs744166) variants may associate with occurrence, severity, and immunosuppressive outcome of AA in the Han population in southwest China.

  9. Associação dos níveis de citocinas no pós-transplante de células-tronco hematopoiéticas com a Doença do Enxerto Contra o Hospedeiro aguda Association of cytokine levels with acute graft versus host disease following full match allogeneic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Jeane E. L. Visentainer

    2005-09-01

    group who developed acute GVHD than in the group without acute GVHD. Soluble IL-2R levels increased in direct correlation to engraftment and onset of acute GVHD, while IL-10 levels increased transiently following transplantation. The mean TNF-alpha concentration in the first weeks after transplantation was augmented in the group that developed acute GVHD. Furthermore, a drop in TGF-beta1 levels after the engraftment was significantly associated to acute GVHD. No correlation was found between acute GVHD and the other evaluated cytokines. These results support the idea that a balance between cytokines derived from type 1 and type 2 T-helper cells may be important in the development and control of acute GVHD. Although sIL-2R, TNF-alpha, IL-10, and TGF-beta1 levels, correlated with acute GVHD, sIL-2R levels at the engraftment may provide a better parameter for the early detection of acute GVHD after allogeneic stem cell transplantation.

  10. IL-1 family members IL-18 and IL-33 upregulate the inflammatory potential of differentiated human Th1 and Th2 cultures

    DEFF Research Database (Denmark)

    Blom, Lars; Poulsen, Lars K.

    2012-01-01

    The IL-1 family members IL-1ß, IL-18, and IL-33 are potent cytokines in relationship to amplifying the CD4(+) T cell cytokine production. To evaluate their impact on in vitro-differentiated human Th1 and Th2 cultures, such cultures were established from naive T cells, purified from healthy blood...... donors, and reactivated in the presence of IL-1ß, IL-18, or IL-33. Interestingly, we observe modifying responses in Th1 and Th2 cultures induced by IL-18 or IL-33 but not by IL-1ß, both contributing to amplify production of IL-5, IL-13, and IFN-¿. IL-18 or IL-33 stimulation of Th1 cultures resulted...... in increased IFN-¿ and IL-13 production concurrent with reduced IL-10 gene transcription and secretion even though Th1 cultures, in contrast to IL-18Ra, had low ST2L expression. Furthermore, adding IL-18 to Th1 cultures promoted Tbet mRNA expression and production. Th2 cultures stimulated with IL-18 or IL-33...

  11. Arsenite evokes IL-6 secretion, autocrine regulation of STAT3 signaling, and miR-21 expression, processes involved in the EMT and malignant transformation of human bronchial epithelial cells

    International Nuclear Information System (INIS)

    Luo, Fei; Xu, Yuan; Ling, Min; Zhao, Yue; Xu, Wenchao; Liang, Xiao; Jiang, Rongrong; Wang, Bairu; Bian, Qian; Liu, Qizhan

    2013-01-01

    Arsenite is an established human carcinogen, and arsenite-induced inflammation contributes to malignant transformation of cells, but the molecular mechanisms by which cancers are produced remain to be established. The present results showed that, evoked by arsenite, secretion of interleukin-6 (IL-6), a pro-inflammatory cytokine, led to the activation of STAT3, a transcription activator, and to increased levels of a microRNA, miR-21. Blocking IL-6 with anti-IL-6 antibody and inhibiting STAT3 activation reduced miR-21 expression. For human bronchial epithelial cells, cultured in the presence of anti-IL-6 antibody for 3 days, the arsenite-induced EMT and malignant transformation were reversed. Thus, IL-6, acting on STAT3 signaling, which up-regulates miR-21in an autocrine manner, contributes to the EMT induced by arsenite. These data define a link from inflammation to EMT in the arsenite-induced malignant transformation of HBE cells. This link, mediated through miRNAs, establishes a mechanism for arsenite-induced lung carcinogenesis. - Highlights: • Arsenite evokes IL-6 secretion. • IL-6 autocrine mediates STAT3 signaling and up-regulates miR-21expression. • Inflammation is involved in arsenite-induced EMT

  12. A Pilot Study of IL2 in Drug-Resistant Idiopathic Nephrotic Syndrome.

    Directory of Open Access Journals (Sweden)

    Alice Bonanni

    Full Text Available Tregs infusion reverts proteinuria and reduces renal lesions in most animal models of nephrotic syndrome (i.e. Buffalo/Mna, Adriamycin, Promycin, LPS. IL2 up-regulates Tregs and may be an alternative to cell-therapy in this setting. To evaluate a potential role of IL2 as Tregs inducer and proteinuria lowering agent in human nephrotic syndrome we treated 5 nephrotic patients with 6 monthly cycles of low-dose IL2 (1x106 U/m2 first month, 1.5x106 U/m2 following months. The study cohort consisted of 5 children (all boys, 11–17 years resistant to all the available treatments (i.e. steroids, calcineurin inhibitors, mycophenolate, Rituximab. Participants had Focal Segmental Glomerulosclerosis (3 cases or Minimal Change Nephropathy (2 cases. IL2 was safe in all but one patient who had an acute asthma attack after the first IL2 dose and did not receive further doses. Circulating Tregs were stably increased (>10% during the whole study period in 2 cases while were only partially modified in the other two children who started with very low levels and partially responded to single IL2 Proteinuria and renal function were not modified by IL2 at any phase of the study. We concluded that low-dose IL2 given in monthly pulses is safe and modifies the levels of circulating Tregs. This drug may not be able to lower proteinuria or affect renal function in children with idiopathic nephrotic syndrome. We were unable to reproduce in humans the effects of IL2 described in rats and mice reducing de facto the interest on this drug in nephrotic syndrome.ClinicalTrials.gov NCT02455908.

  13. Lysis of endogenously infected CD4+ T cell blasts by rIL-2 activated autologous natural killer cells from HIV-infected viremic individuals.

    Directory of Open Access Journals (Sweden)

    Manuela Fogli

    2008-07-01

    Full Text Available Understanding the cellular mechanisms that ensure an appropriate innate immune response against viral pathogens is an important challenge of biomedical research. In vitro studies have shown that natural killer (NK cells purified from healthy donors can kill heterologous cell lines or autologous CD4+ T cell blasts exogenously infected with several strains of HIV-1. However, it is not known whether the deleterious effects of high HIV-1 viremia interferes with the NK cell-mediated cytolysis of autologous, endogenously HIV-1-infected CD4+ T cells. Here, we stimulate primary CD4+ T cells, purified ex vivo from HIV-1-infected viremic patients, with PHA and rIL2 (with or without rIL-7. This experimental procedure allows for the significant expansion and isolation of endogenously infected CD4+ T cell blasts detected by intracellular staining of p24 HIV-1 core antigen. We show that, subsequent to the selective down-modulation of MHC class-I (MHC-I molecules, HIV-1-infected p24(pos blasts become partially susceptible to lysis by rIL-2-activated NK cells, while uninfected p24(neg blasts are spared from killing. This NK cell-mediated killing occurs mainly through the NKG2D activation pathway. However, the degree of NK cell cytolytic activity against autologous, endogenously HIV-1-infected CD4+ T cell blasts that down-modulate HLA-A and -B alleles and against heterologous MHC-I(neg cell lines is particularly low. This phenomenon is associated with the defective surface expression and engagement of natural cytotoxicity receptors (NCRs and with the high frequency of the anergic CD56(neg/CD16(pos subsets of highly dysfunctional NK cells from HIV-1-infected viremic patients. Collectively, our data demonstrate that the chronic viral replication of HIV-1 in infected individuals results in several phenotypic and functional aberrancies that interfere with the NK cell-mediated killing of autologous p24(pos blasts derived from primary T cells.

  14. Intravenously delivered graphene nanosheets and multiwalled carbon nanotubes induce site-specific Th2 inflammatory responses via the IL-33/ST2 axis.

    Science.gov (United States)

    Wang, Xiaojia; Podila, Ramakrishna; Shannahan, Jonathan H; Rao, Apparao M; Brown, Jared M

    2013-01-01

    Carbon-based nanomaterials (CBN), such as graphene nanosheets (GNS) and multiwalled carbon nanotubes (MWCNT), have been proposed for potential nanomedicine applications such as biomedical devices and carriers for drug delivery. However, our current understanding regarding the systemic toxicity of these CBN through intravenous (iv) injection is limited. In this study, we compare the immune response resulting from GNS and MWCNT exposure. We hypothesize that iv administration of GNS and MWCNT would result in divergent systemic inflammatory responses due to physicochemical differences between these two CBN. In the lungs of C57BL/6 mice, GNS actuate a Th2 immune response 1 day following iv administration, which consists of neutrophilic influx and a significant increase in interleukin (IL)-5, IL-13, IL-33, and its soluble receptor (sST2) in the bronchoalveolar lavage fluid. MWCNT elicited a significant increase in the messenger ribonucleic acid expression of cytokines in the spleen including IL-4 and IL-33, which are associated with an increase in splenic cell differentiation (CD)4(+) and CD8(+) T-cells in C57BL/6 mice following iv injection. The observed Th2 responses in both the lung and spleen are absent in ST2(-/-) mice administrated GNS or MWCNT, suggesting a critical role for IL-33. In conclusion, the use of GNS or MWCNT as nanocarriers for drug delivery may result in Th2 immune responses that are mediated through the IL-33/ST2 axis and therefore may promote adverse allergic reactions.

  15. Polycyclic aromatic hydrocarbons reciprocally regulate IL-22 and IL-17 cytokines in peripheral blood mononuclear cells from both healthy and asthmatic subjects.

    Directory of Open Access Journals (Sweden)

    Coline Plé

    Full Text Available Pollution, including polycyclic aromatic hydrocarbons (PAH, may contribute to increased prevalence of asthma. PAH can bind to the Aryl hydrocarbon Receptor (AhR, a transcription factor involved in Th17/Th22 type polarization. These cells produce IL17A and IL-22, which allow neutrophil recruitment, airway smooth muscle proliferation and tissue repair and remodeling. Increased IL-17 and IL-22 productions have been associated with asthma. We hypothesized that PAH might affect, through their effects on AhR, IL-17 and IL-22 production in allergic asthmatics. Activated peripheral blood mononuclear cells (PBMCs from 16 nonallergic nonasthmatic (NA and 16 intermittent allergic asthmatic (AA subjects were incubated with PAH, and IL-17 and IL-22 productions were assessed. At baseline, activated PBMCs from AA exhibited an increased IL-17/IL-22 profile compared with NA subjects. Diesel exhaust particle (DEP-PAH and Benzo[a]Pyrene (B[a]P stimulation further increased IL-22 but decreased IL-17A production in both groups. The PAH-induced IL-22 levels in asthmatic patients were significantly higher than in healthy subjects. Among PBMCs, PAH-induced IL-22 expression originated principally from single IL-22- but not from IL-17- expressing CD4 T cells. The Th17 transcription factors RORA and RORC were down regulated, whereas AhR target gene CYP1A1 was upregulated. IL-22 induction by DEP-PAH was mainly dependent upon AhR whereas IL-22 induction by B[a]P was dependent upon activation of PI3K and JNK. Altogether, these data suggest that DEP-PAH and B[a]P may contribute to increased IL22 production in both healthy and asthmatic subjects through mechanisms involving both AhR -dependent and -independent pathways.

  16. The Association of Circulating MiR-29b and Interleukin-6 with Subclinical Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Yu-qing Huang

    2017-12-01

    Full Text Available Background/Aims: Although it is widely acknowledged that atherosclerosis is mainly a chronic inflammatory process, in which both miR-29b and interleukin-6 (IL-6 play multifaceted roles, the association between miR-29b and IL-6 remains unknown. The aim of the present study was to explore the relationship between miR-29b and IL-6 and to test whether circulating levels of miR-29b and IL-6 could predict atherosclerosis. Methods: A total of 170 participants were divided into two groups according to carotid intima-media thickness (CIMT: study group (CIMT ≥ 0.9mm and control group (CIMT < 0.9mm. Levels of circulating miR-29b and IL-6 were measured by quantitative real-time polymerase chain reaction (qRT-PCR and enzyme-linked immunosorbent assay (ELISA, respectively. The association of miR-29b and IL-6 levels with CIMT was assessed using Spearman correlation analysis and multiple linear regression analysis. Results: The study group showed higher miR-29b levels (31.61 ± 3.05 vs. 27.91 ± 1.71 Ct, p < 0.001 and IL-6 levels (3.40 ± 0.67 vs. 2.99 ± 0.37 pg/ml, p < 0.001, compared with the control group. CIMT was positively correlated with miR-29b (r = 0.587, p < 0.001 and IL-6 (r = 0.410, p < 0.001, and miR-29b levels were also correlated with IL-6 (r = 0.242, p = 0.001. Multiple linear regression analysis also showed that CIMT was positively correlated with miR-29b and IL-6. After adjustment for age, body mass index, systolic blood pressure, total cholesterol and C-reactive protein, CIMT was still closely correlated with miR-29b and IL-6. The combination of miR-29b and IL-6 (AUC = 0.901, p < 0.001 offered a better predictive index for atherosclerosis than either miR-29b (AUC = 0.867, p < 0.001 or IL-6 (AUC = 0.747, p < 0.001 alone. Conclusion: Circulating levels of miR-29b and IL-6 may be independently correlated with subclinical atherosclerosis, and may serve as novel biomarkers for the identification of atherosclerosis.

  17. Increased systemic and epidermal levels of IL-17A and IL-1β promotes progression of non-segmental vitiligo.

    Science.gov (United States)

    Bhardwaj, Supriya; Rani, Seema; Srivastava, Niharika; Kumar, Ravinder; Parsad, Davinder

    2017-03-01

    Non-segmental vitiligo (NSV) results from autoimmune destruction of melanocytes. The altered levels of various cytokines have been proposed in the pathogenesis of vitiligo. However, the exact immune mechanisms have not yet been fully elucidated. To investigate the role of epidermal and systemic cytokines in active and stable NSV patients. Serum levels of inflammatory cytokines were checked in 42 active and 30 stable NSV patients with 30 controls. The lesional, perilesional and normal skin sections were subjected to H&E staining. The mRNA expression of inflammatory cytokines and their respective receptors were assessed by quantitative PCR in lesional skin of both active and stable NSV skin. The MITF and IL-17A were immunolocalized in lesional, perilesional and normal skin tissue. Significant increase in the expression of inflammatory cytokines, IL-17A, IL-1β and TGF-β was observed in active patients, whereas no change was observed in stable patients. A marked reduction in epidermal thickness was observed in lesional skin sections. Significant increase in IL-17A and significant decrease in microphthalmia associated transcription factor (MITF) expression was observed in lesional and perilesional skin sections. Moreover, qPCR analysis showed significant alterations in the mRNA levels of IL-17A, IL-1β, IFN-γ, TGF-β and their respective receptors in active and stable vitiligo patient samples. Increased levels of IL-17A and IL-1β cytokines and decreased expression of MITF suggested a possible role of these cytokines in dysregulation of melanocytic activity in the lesional skin and hence might be responsible for the progression of active vitiligo. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. IL-27 Induced by Select Candida spp. via TLR7/NOD2 Signaling and IFN-β Production Inhibits Fungal Clearance

    Science.gov (United States)

    Patin, Emmanuel C.; Jones, Adam V.; Thompson, Aiysha; Clement, Mathew; Liao, Chia-Te; Griffiths, James S.; Wallace, Leah E.; Bryant, Clare E.; Lang, Roland; Rosenstiel, Philip; Humphreys, Ian R.; Taylor, Philip R.

    2016-01-01

    Candida spp. elicit cytokine production downstream of various pathogen recognition receptors, including C-type lectin-like receptors, TLRs, and nucleotide oligomerization domain (NOD)–like receptors. IL-12 family members IL-12p70 and IL-23 are important for host immunity against Candida spp. In this article, we show that IL-27, another IL-12 family member, is produced by myeloid cells in response to selected Candida spp. We demonstrate a novel mechanism for Candida parapsilosis–mediated induction of IL-27 in a TLR7-, MyD88-, and NOD2-dependent manner. Our data revealed that IFN-β is induced by C. parapsilosis, which in turn signals through the IFN-α/β receptor and STAT1/2 to induce IL-27. Moreover, IL-27R (WSX-1)–deficient mice systemically infected with C. parapsilosis displayed enhanced pathogen clearance compared with wild-type mice. This was associated with increased levels of proinflammatory cytokines in the serum and increased IFN-γ and IL-17 responses in the spleens of IL-27R–deficient mice. Thus, our data define a novel link between C. parapsilosis, TLR7, NOD2, IFN-β, and IL-27, and we have identified an important role for IL-27 in the immune response against C. parapsilosis. Overall, these findings demonstrate an important mechanism for the suppression of protective immune responses during infection with C. parapsilosis, which has potential relevance for infections with other fungal pathogens. PMID:27259855

  19. The Relationship Between Serum Levels of Total IgE, IL-18, IL-12, IFN- γ and Disease Severity in Children With Atopic Dermatitis

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available Studies about the role of cytokines on the immunopathogenesis of atopic dermatitis (AD are generally based on in vitro observations and this role has not been completely clarified yet. Serum levels of total IgE, IL-18, IL-12, IFN- γ and the relationship between these parameters and disease severity, determined using the SCORAD index, in a group of atopic patients were investigated in this study. Serum levels of total IgE were measured by the nephelometric method and serum levels of IL-18, IL-12/p40 and IFN- γ were measured by ELISA method. Serum levels of total IgE and IL-18 were found significantly higher in study group than in controls ( p<.001 . There was no statistically significant difference between patients and controls in respect of serum levels of IL-12/p40 ( p=.227 . A statistically significant relationship between SCORAD values and serum levels of total IgE ( p<.001 , IL-18 ( p<.001 , and IL-12/p40 ( p<.001 was determined. These results show that serum levels of IL-18 can be a sensitive parameter that importantly correlates with clinical severity of AD, can play a role in the immunopathogenesis of AD, and furthermore may be used in the diagnosis and follow-up of the disease in addition to other parameters.

  20. The diagnostic role of serum inflammatory and soluble proteins on dementia subtypes: correlation with cognitive and functional decline.

    Science.gov (United States)

    Oztürk, Candan; Ozge, Aynur; Yalin, Osman Ozgür; Yilmaz, I Arda; Delialioglu, Nuran; Yildiz, Cilem; Tesdelen, Bahar; Kudiaki, Cigdem

    2007-01-01

    In the past years, the possible involvement of inflammation in the pathogenesis of dementia has been the subject of several investigations. However there are restricted data about the profile of the inflammatory and soluble proteins in well evaluated Alzheimer's disease (AD), vascular dementia (VD), mild cognitive impairment (MCI) and healthy controls. There are also no reliable data regarding the relationship between the overlapping protein levels and cognitive or functional decline. We measured levels of IL-1beta, IL-2, IL-6, IL-18, TNF-alpha, beta-Amlyloid 1-40 and alpha1-antichymotrypsin levels in plasma in groups of total 82 subjects with AD, MCI, VD and controls using enzyme-linked immunosorbent assay (ELISA) method. Our study samples showed high levels of proinflammatory cytokine levels (especially IL-18) in all patient groups but only high levels of alpha1-antichymotrypsine in VD patients compared to controls. There is no significant correlation between the laboratory and clinical variables except for a link between IL-1beta and NPI scores of AD. In conclusion, this study yielded evidence of some shared mechanisms underlying AD and VD and thus motivates further studies of inflammatory markers in various types of dementia and MCI.

  1. The HLA-G genotype is associated with IL-10 levels in activated PBMCs

    DEFF Research Database (Denmark)

    Rizzo, Roberta; Hviid, Thomas Vauvert F; Stignani, Marina

    2005-01-01

    ) in lipopolysaccharide (LPS)-activated peripheral blood mononuclear lymphocytes (PBMCs) in relation to the HLA-G 14 bp genotype. No HLA-G5/sHLA-G1 could be detected in the non-activated control PBMC culture media, and there were no significant differences among the three HLA-G 14 bp genotypes regarding IL-10...... concentrations. In LPS-activated PBMC cultures, no significant differences among the three HLA-G 14 bp genotypes regarding HLA-G5/sHLA-G1 concentrations were observed. However, this was in contrast to the IL-10 levels (P=0.0004, Kruskal-Wallis test). The +14/+14 bp PBMC samples expressed higher levels of IL-10...... when compared to the -14/+14 bp genotype and the -14/-14 bp genotype. Interestingly, the IL-10 G/G polymorphism at position -1082 was more frequent in the +14/+14 bp genotype (P=0.024, chi2 test). These results support an autocrine loop between HLA-G5/sHLA-G1 and IL-10 expression in activated PBMCs...

  2. Issues concerning the determination of solubility products of sparingly soluble crystalline solids. Solubility of HfO2(cr)

    International Nuclear Information System (INIS)

    Rai, Dhanpat; Kitamura, Akira; Rosso, Kevin M.; Sasaki, Takayuki; Kobayashi, Taishi

    2016-01-01

    Solubility studies were conducted with HfO 2 (cr) solid as a function HCl and ionic strength ranging from 2.0 to 0.004 mol kg -1 . These studies involved (1) using two different amounts of the solid phase, (2) acid washing the bulk solid phase, (3) preheating the solid phase to 1400 C, and (4) heating amorphous HfO 2 (am) suspensions to 90 C to ascertain whether the HfO 2 (am) converts to HfO 2 (cr) and to determine the solubility from the oversaturation direction. Based on the results of these treatments it is concluded that the HfO 2 (cr) contains a small fraction of less crystalline, but not amorphous, material [HfO 2 (lcr)] and this, rather than the HfO 2 (cr), is the solubility-controlling phase in the range of experimental variables investigated in this study. The solubility data are interpreted using both the Pitzer and SIT models and they provide log 10 K 0 values of -(59.75±0.35) and -(59.48±0.41), respectively, for the solubility product of HfO 2 (lcr)[HfO 2 (lcr) + 2H 2 O ↔ Hf 4+ + 4OH - ]. The log 10 of the solubility product of HfO 2 (cr) is estimated to be < -63. The observation of a small fraction of less crystalline higher solubility material is consistent with the general picture that mineral surfaces are often structurally and/or compositionally imperfect leading to a higher solubility than the bulk crystalline solid. This study stresses the urgent need, during interpretation of solubility data, of taking precautions to make certain that the observed solubility behavior for sparingly-soluble solids is assigned to the proper solid phase.

  3. Urinary excretion levels of water-soluble vitamins in pregnant and lactating women in Japan.

    Science.gov (United States)

    Shibata, Katsumi; Fukuwatari, Tsutomu; Sasaki, Satoshi; Sano, Mitsue; Suzuki, Kahoru; Hiratsuka, Chiaki; Aoki, Asami; Nagai, Chiharu

    2013-01-01

    Recent studies have shown that the urinary excretion levels of water-soluble vitamins can be used as biomarkers for the nutritional status of these vitamins. To determine changes in the urinary excretion levels of water-soluble vitamins during pregnant and lactating stages, we surveyed and compared levels of nine water-soluble vitamins in control (non-pregnant and non-lactating women), pregnant and lactating women. Control women (n=37), women in the 2nd (16-27 wk, n=24) and 3rd trimester of pregnancy (over 28 wk, n=32), and early- (0-5 mo, n=54) and late-stage lactating (6-11 mo, n=49) women took part in the survey. The mean age of subjects was ~30 y, and mean height was ~160 cm. A single 24-h urine sample was collected 1 d after the completion of a validated, self-administered comprehensive diet history questionnaire to measure water-soluble vitamins or metabolites. The average intake of each water-soluble vitamin was ≍ the estimated average requirement value and adequate intake for the Japanese Dietary Reference Intakes in all life stages, except for vitamin B6 and folate intakes during pregnancy. No change was observed in the urinary excretion levels of vitamin B2, vitamin B6, vitamin B12, biotin or vitamin C among stages. Urine nicotinamide and folate levels were higher in pregnant women than in control women. Urine excretion level of vitamin B1 decreased during lactation and that of pantothenic acid decreased during pregnancy and lactation. These results provide valuable information for setting the Dietary Reference Intakes of water-soluble vitamins for pregnant and lactating women.

  4. IL-21-secreting hUCMSCs combined with miR-200c inhibit tumor growth and metastasis via repression of Wnt/β-catenin signaling and epithelial-mesenchymal transition in epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2018-04-01

    Full Text Available Yunxia Zhang,1,2 Jing Wang,2 Di Wu,1 Miao Li,1 Fenshu Zhao,1 Mulan Ren,2 Yunlong Cai,2 Jun Dou1 1Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Department of Gynecology & Obstetrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China Background: Epithelial ovarian cancer (EOC with insidious characteristic manifests no symptoms in its early onset but most patients have advanced and distant cancer metastasis at diagnosis. Innovative early diagnosis and effective treatment of EOC are urgently needed. Methods: In the study, we developed a novel agent of IL-21-secreting human umbilical cord mesenchymal stem cells (hUCMSCs combined with miR-200c to evaluate its effects on SKOV3 EOC in vitro and in vivo.Results: hUCMSCs-LV-IL-21 combined with miR-200c significantly inhibited the SKOV3 cell mobility and tumorigenesis compared with hUCMSCs-LV-IL-21, hUCMSCs- LV-vector, and hUCMSCs, respectively. These were reflected in decreasing the tumor sizes and elongating the tumor bearing nude mouse survival, accompanied with increasing the serum cytokine levels of IFN-γ, IL-21 and TNF-α as well as the splenocyte cytotoxicity. In addition, the expression of β-catenin, cyclin-D1, Gli1, Gli2, and ZEB1 was decreased but the E-cadherin expression was increased in tumor tissues of mice treated with hUCMSCs-LV-IL-21 plus miR-200c.Conclusion: We demonstrated that the synergistic effect of fighting SKOV3 EOC is attributable to repression of Wnt/β-catenin signaling and epithelial-mesenchymal transition in SKOV3 EOC. The findings may provide a new strategy for therapy of EOC. Keywords: epithelial ovarian cancer, umbilical cord mesenchymal stem cells, IL-21, miR-200c, Wnt/β-catenin signaling, epithelial–mesenchymal transition

  5. Obese with higher FNDC5/Irisin levels have a better metabolic profile, lower lipopolysaccharide levels and type 2 diabetes risk.

    Science.gov (United States)

    Bonfante, Ivan Luiz Padilha; Chacon-Mikahil, Mara Patricia Traina; Brunelli, Diego Trevisan; Gáspari, Arthur Fernandes; Duft, Renata Garbellini; Oliveira, Alexandre Gabarra; Araujo, Tiago Gomes; Saad, Mario Jose Abdalla; Cavaglieri, Cláudia Regina

    2017-12-01

    Thus, the aim of this study was to compare if higher or smaller fibronectin type 3 domain-containing protein 5 (FNDC5)/irisin levels are associated with inflammatory and metabolic markers, caloric/macronutrient intake, physical fitness and type 2 diabetes mellitus (T2DM) risk in obese middle-aged men, and also to correlate all variables analyzed with FNDC5/irisin. On the basis of a cluster study, middle-aged obese men (IMC: 31.01 ± 1.64 kg/m2) were divided into groups of higher and smaller levels of FNDC5/irisin. The levels of leptin, resistin, adiponectin, tumor necrosis factor alpha (TNFα), interleukin 6 and 10 (IL6, IL10), lipopolysaccharide (LPS), glucose, insulin, glycated hemoglobin, insulin resistance and sensibility, lipid profile, risk of T2DM development, body composition, rest energy expenditure, caloric/macronutrient intake and physical fitness were measured. The higher FNDC5/ irisin group presented improved insulin sensibility (homeostasis model assessment - sensibility (HOMA-S) (p = 0.01) and QUICKI index (p risk of T2DM development (p = 0.02), tendency to decrease serum resistin (p = 0.08) and significant lower LPS levels (p = 0.02). Inverse correlations between FNDC5/irisin and body weight (r -0.46, p = 0.04), neck circumference (r -0.51, p = 0.02), free fat mass (r -0.49, p = 0.02), triglycerides (r -0.43, p = 0.05) and risk of developing T2DM (r -0.61, p = 0.04) were observed. These results suggest that higher FNDC5/irisin levels in obese middle-aged men are related to a better metabolic profile and lower risk of T2DM development and serum LPS, a potential inducer of insulin resistance.

  6. High pressure solubility data of carbon dioxide in (tri-iso-butyl(methyl)phosphonium tosylate + water) systems

    Energy Technology Data Exchange (ETDEWEB)

    Ventura, Sonia P.M. [CICECO, Departamento de Quimica, Universidade de Aveiro, 3810-193 Aveiro (Portugal); Pauly, Jerome; Daridon, Jean L. [Laboratoire Haute Pression Centre Universitaire de Recherche Scientifique, Universite de Pau, Avenue de l' Universite, 64000 Pau (France); Lopes da Silva, J.A.; Marrucho, Isabel M. [CICECO, Departamento de Quimica, Universidade de Aveiro, 3810-193 Aveiro (Portugal); Dias, Ana. M.A. [IBB-Instituto de Biotecnologia e Bioengenharia, Centro de Engenharia Biologica, Universidade do Minho, Campus de Gualtar, 4710-553 Braga (Portugal); Coutinho, Joao A.P. [CICECO, Departamento de Quimica, Universidade de Aveiro, 3810-193 Aveiro (Portugal)], E-mail: jcoutinho@ua.pt

    2008-08-15

    Ionic liquids are attracting great attention nowadays due to their interesting properties which make them useful in a broad range of applications including reaction media or separation/capture of environmentally hazardous gases such as carbon dioxide. In many cases, for practical and/or economical reasons, the use of aqueous solutions of ILs would be preferable to their use as pure compounds. In this work, high pressure equilibrium data for the {l_brace}carbon dioxide (CO{sub 2}) + tri-iso-butyl(methyl)phosphonium tosylate [iBu{sub 3}MeP][TOS] + water system were measured at temperatures ranging from (276 to 370) K and pressures up to 100 MPa. Measurements were performed using a high-pressure cell with a sapphire window that allows direct observation of the liquid-vapour transition. Mixtures with different IL concentrations were studied in order to check the influence of the amount of IL on the solubility of CO{sub 2} in the aqueous mixture. The results show that the presence of IL enhances the solubility of CO{sub 2} in the (IL + water) system revealing a salting-in effect of the IL on the solubility of CO{sub 2}. The appearance of a three phase region was observed for IL concentrations higher than 4 mol% of IL in water when working at pressures between 4 and 8 MPa and temperatures between (280 and 305) K. In this range, the upper limit of the VLE region observed is shown to increase with the temperature being almost independent of the IL initial concentration in the mixture.

  7. Detection of levels of VEGF and IL-6 in the aqueous humor of patients with diabetic retinopathy and its clinical significance%糖尿病视网膜病变患者房水VEGF和IL-6水平的测定及其临床意义

    Institute of Scientific and Technical Information of China (English)

    周林; 康建芳; 冯军; 徐岬

    2011-01-01

    目的 探讨糖尿病视网膜病变(DR)程度与房水中血管内皮生长因子(VEGF)和白细胞介素-6(IL-6)含量之间的关系.方法 采用双抗体夹心酶联免疫吸附(EIISA)法,测定88例房水中VEGF和IL-6的含量,根据散瞳眼底检查和眼底荧光素血管造影检查后,实验组分为:无糖尿病视网膜病变组(NDR)21例、单纯型糖尿病性视网膜病变组(BDR)27例、增生型糖尿病性视网膜病变组(PDR)20例;对照组为健康的老年性白内障患者20例.结果 NDR组、BDR组、PDR组的房水VEGF含量分别为(240.29±26.14)pg/ml、(292.32±58.43)pg/ml、(477.65±90.08)pg/ml,IL-6含量分别为(160.81±33.40)pg/ml、(238.82±62.01)pg/ml、(389.42±90.08)pg/ml;对照组房水VEGF含量为(140.56±26.24)pg/ml、IL-6含量为(82.74±21.51)pg/ml,对照组与实验组比较差异均有统计学意义(F=113.67,P<0.01;F=106.53,P<0.01).各组房水VEGF和IL-6含量有明显增加的趋势.房水中的VEGF含量与相应的IL-6含量有统计学意义(r=0.995,P<0.01);房水中VEGF、IL-6含量与糖尿病患者的病程及糖尿病视网膜病变的严重程度差异有统计学意义(r=0.722,P=0.01;r=792,P<0.01)、(r 0.869,P<0.01;r=0.865,P<0.01).结论 VEGF、IL-6在糖尿病视网膜病变的形成过程中有重要作用,且两者之间有相关性.%Objective To explore the relationship between diabetic retinopathy (DR) and vascular endothelial growth factor (VEGF), interleukin-6 (IL-6) levels in the aqueous humor. Methods Aqueous humor samples were collected from diabetic patients with cataracts or without retinopathy, and aqueous humor samples from non-diabetic patients with cataracts were chosen as controls. The content of VEGF in the aqueous humor was determined by using the ELISA technique. Results The level of VEGF in the aqueous humor samples of diabetic patients without retinopathy (NDR), background diabetic retinopathy (BDR) and proliferative diabetic retinopathy (PDR) were (240.29± 26.14) pg/ml, (292.32

  8. Clinical significance of determination of changes of serum IGF-II, IL-6, IL-8 and hs-CRP levels after treatment in pediatric patients with bronchopneumonia

    International Nuclear Information System (INIS)

    Wang Guanghui; Chen Chuanbing; Wang Xianwu

    2009-01-01

    Objective: To explore the clinical significance of changes of serum IGF-II, IL-6, IL-8 and hs-CRP levels after treatment in pediatric patients with bronchopneumonia. Methods: Serum IGF-II, IL-6, IL-8 (with RIA) and hs-CRP (with immunoturbidity method) levels were determined in 36 pediatric patients with bronchopneumonia both before and after treatment as well as in 35 controls. Results: Before treatment, serum IGF-II, IL-6, IL-8 and hs-CRP levels in the patients were significantly higher than those in the controls (P 0.05). Conclusion: Determination of serum IGF-II, IL-6, IL-8 and hs-CRP levels in pediatric patients with bronchopneumonia was important for diagnosis and outcome prediction. (authors)

  9. DMPD: Pellino proteins: novel players in TLR and IL-1R signalling. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17635639 Pellino proteins: novel players in TLR and IL-1R signalling. Schauvliege R..., Janssens S, Beyaert R. J Cell Mol Med. 2007 May-Jun;11(3):453-61. (.png) (.svg) (.html) (.csml) Show Pellino proteins: novel player...s in TLR and IL-1R signalling. PubmedID 17635639 Title Pellino proteins: novel player...tml) CSML File (.csml) Open .csml file with CIOPlayer Open .csml file with CIOPlayer - ※CIO Playerのご利用上の注意 Open .csml file with CIO Open .csml file with CIO - ※CIOのご利用上の注意 ...

  10. Identification de Staphylococcus aureus : est-il possible de réduire ...

    African Journals Online (AJOL)

    SARAH

    31 janv. 2014 ... influencer la recherche de la staphylocoagulase libre ? 6027. Identification de Staphylococcus aureus : est-il possible de réduire le volume de plasma de lapin sans influencer la recherche de la staphylocoagulase libre ? Bankolé H.S., Dougnon T.V., Fiogbé E.P., Amoussou A.N., Baba-Moussa L.

  11. Airway delivery of soluble factors from plastic-adherent bone marrow cells prevents murine asthma.

    Science.gov (United States)

    Ionescu, Lavinia I; Alphonse, Rajesh S; Arizmendi, Narcy; Morgan, Beverly; Abel, Melanie; Eaton, Farah; Duszyk, Marek; Vliagoftis, Harissios; Aprahamian, Tamar R; Walsh, Kenneth; Thébaud, Bernard

    2012-02-01

    Asthma affects an estimated 300 million people worldwide and accounts for 1 of 250 deaths and 15 million disability-adjusted life years lost annually. Plastic-adherent bone marrow-derived cell (BMC) administration holds therapeutic promise in regenerative medicine. However, given the low cell engraftment in target organs, including the lung, cell replacement cannot solely account for the reported therapeutic benefits. This suggests that BMCs may act by secreting soluble factors. BMCs also possess antiinflammatory and immunomodulatory properties and may therefore be beneficial for asthma. Our objective was to investigate the therapeutic potential of BMC-secreted factors in murine asthma. In a model of acute and chronic asthma, intranasal instillation of BMC conditioned medium (CdM) prevented airway hyperresponsiveness (AHR) and inflammation. In the chronic asthma model, CdM prevented airway smooth muscle thickening and peribronchial inflammation while restoring blunted salbutamol-induced bronchodilation. CdM reduced lung levels of the T(H)2 inflammatory cytokines IL-4 and IL-13 and increased levels of IL-10. CdM up-regulated an IL-10-induced and IL-10-secreting subset of T regulatory lymphocytes and promoted IL-10 expression by lung macrophages. Adiponectin (APN), an antiinflammatory adipokine found in CdM, prevented AHR, airway smooth muscle thickening, and peribronchial inflammation, whereas the effect of CdM in which APN was neutralized or from APN knock-out mice was attenuated compared with wild-type CdM. Our study provides evidence that BMC-derived soluble factors prevent murine asthma and suggests APN as one of the protective factors. Further identification of BMC-derived factors may hold promise for novel approaches in the treatment of asthma.

  12. Low expression of IL-18 and IL-18 receptor in human skeletal muscle is associated with systemic and intramuscular lipid metabolism-Role of HIV lipodystrophy

    DEFF Research Database (Denmark)

    Lindegaard, Birgitte; Hvid, Thine; Wolsk Mygind, Helene

    2018-01-01

    receptor (R) expression would be altered in patients with HIV-lipodystrophy. DESIGN AND METHODS: Twenty-three HIV-infected patients with LD and 15 age-matched healthy controls were included in a cross-sectional study. Biopsies from the vastus lateralis muscle were obtained and IL-18 and IL-18R m......-18 mRNA is expressed in human skeletal muscle but a role for IL-18 in muscle has not been identified. Patients with HIV-infection and lipodystrophy (LD) are characterized by lipid and glucose disturbances and increased levels of circulating IL-18. We hypothesized that skeletal muscle IL-18 and IL-18......RNA expression were measured by real-time PCR and sphingolipids (ceramides, sphingosine, sphingosine-1-Phosphate, sphinganine) were measured by HPLC. Insulin resistance was assessed by HOMA and the insulin response during an OGTT. RESULTS: Patients with HIV-LD had a 60% and 54% lower level of muscular IL-18...

  13. Soluble ligands for the NKG2D receptor are released during endometriosis and correlate with disease severity.

    Directory of Open Access Journals (Sweden)

    Iñaki González-Foruria

    Full Text Available Endometriosis is a benign gynaecological disease. Abundant bulk of evidence suggests that patients with endometriosis have an immunity dysfunction that enables ectopic endometrial cells to implant and proliferate. Previous studies show that natural killer cells have a pivotal role in the immune control of endometriosis.This is a prospective laboratory study conducted in a tertiary-care university hospital between January 2011 and April 2013. We investigated non-pregnant, younger than 42-year-old patients (n= 202 during surgery for benign gynaecological conditions. After complete surgical exploration of the abdominopelvic cavity, 121 women with histologically proven endometriosis and 81 endometriosis-free controls women were enrolled. Patients with endometriosis were classified according to a surgical classification in three different types of endometriosis: superficial peritoneal endometriosis (SUP, ovarian endometrioma (OMA and deep infiltrating endometriosis (DIE. Peritoneal fluid samples were obtained from all study participants during the surgery in order to detect soluble NKG2D ligands (MICA, MICB and ULBP-2. When samples with undetectable peritoneal fluid levels of MICA, MICB and ULBP-2 were excluded, MICA ratio levels were significantly higher in endometriosis patients than in controls (median, 1.1 pg/mg; range, 0.1-143.5 versus median, 0.6 pg/mg; range, 0.1-3.5; p=0.003. In a similar manner peritoneal fluid MICB levels were also increased in endometriosis-affected patients compared with disease-free women (median, 4.6 pg/mg; range, 1.2-4702 versus median, 3.4 pg/mg; range, 0.7-20.1; p=0.001. According to the surgical classification, peritoneal fluid soluble MICA, MICB and ULBP-2 ratio levels were significantly increased in DIE as compared to controls (p=0.015, p=0.003 and p=0.045 respectively. MICA ratio levels also correlated with dysmenorrhea (r=0.232; p=0.029, total rAFS score (r=0.221; p=0.031 and adhesions rAFS score (r=0.221; p=0

  14. IL-21 Modulates Activation of NKT Cells in Patients with Stage IV Malignant Melanoma.

    Science.gov (United States)

    Coquet, Jonathan M; Skak, Kresten; Davis, Ian D; Smyth, Mark J; Godfrey, Dale I

    2013-10-01

    Interleukin-21 (IL-21) is a common γ-chain cytokine produced by T helper and natural killer T (NKT) cells. It has been shown to regulate the response of various lymphocyte subsets including NK, NKT, T and B cells. Owing to its potent anti-tumor function in preclinical studies and its ability to induce cytotoxicity and interferon-γ (IFN-γ) production in NK and CD8 T cells, recombinant IL-21 (rIL-21) was fast-tracked into early-phase clinical trials of patients with various malignancies. In a phase 2a trial of patients with metastatic melanoma, we analyzed the frequency and function of NKT cells in patients receiving rIL-21. NKT cells were present at a low frequency, but their levels were relatively stable in patients administered rIL-21. Unlike our observations in NK and CD8 T cells, rIL-21 appeared to reduce IFN-γ and TNF production by NKT cells, whereas it enhanced IL-4 production. It also modulated the expression of cell surface markers, specifically on CD4(-) NKT cells. In addition, an increase in CD3(+)CD56(+) NKT-like cells was observed over the course of rIL-21 administration. These results highlight that IL-21 is a potent regulator of NKT cell function in vivo.

  15. Role of the IL-12/IL-35 balance in patients with Sjögren syndrome.

    Science.gov (United States)

    Fogel, Olivier; Rivière, Elodie; Seror, Raphaèle; Nocturne, Gaetane; Boudaoud, Saida; Ly, Bineta; Gottenberg, Jacques-Eric; Le Guern, Véronique; Dubost, Jean-Jacques; Nititham, Joanne; Taylor, Kimberly E; Chanson, Philippe; Dieudé, Philippe; Criswell, Lindsey A; Jagla, Bernd; Thai, Alice; Mingueneau, Michael; Mariette, Xavier; Miceli-Richard, Corinne

    2017-09-12

    An interferon signature is involved in the pathogenesis of primary Sjögren syndrome (pSS), but whether the signature is type 1 or type 2 remains controversial. Mouse models and genetic studies suggest the involvement of T H 1 and type 2 interferon pathways. Likewise, polymorphisms of the IL-12A gene (IL12A), which encodes for IL-12p35, have been associated with pSS. The IL-12p35 subunit is shared by 2 heterodimers: IL-12 and IL-35. We sought to confirm genetic association of the IL12A polymorphism and pSS and elucidate involvement of the IL-12/IL-35 balance in patients with pSS by using functional studies. The genetic study involved 673 patients with pSS from 2 French pSS cohorts and 585 healthy French control subjects. Functional studies were performed on sorted monocytes, irrespective of whether they were stimulated. IL12A mRNA expression and IL-12 and IL-35 protein levels were assessed by using quantitative RT-PCR and ELISA and a multiplex kit for IL-35 and IL-12, respectively. We confirmed association of the IL12A rs485497 polymorphism and pSS and found an increased serum protein level of IL-12p70 in patients with pSS carrying the risk allele (P = .016). Serum levels of IL-12p70 were greater in patients than control subjects (P = .0001), especially in patients with more active disease (P = .05); conversely, IL-35 levels were decreased in patients (P = .0001), especially in patients with more active disease (P = .05). In blood cellular subsets both IL12p35 and EBV-induced gene protein 3 (EBI3) mRNAs were detected only in B cells, with a trend toward a lower level among patients with pSS. Our findings emphasize involvement of the IL-12/IL-35 balance in the pathogenesis of pSS. Serum IL-35 levels were associated with low disease activity, in contrast with serum IL-12p70 levels, which were associated with more active disease. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  16. Chronic administration of recombinant IL-6 upregulates lipogenic enzyme expression and aggravates high-fat-diet-induced steatosis in IL-6-deficient mice

    Directory of Open Access Journals (Sweden)

    Margarita Vida

    2015-07-01

    Full Text Available Interleukin-6 (IL-6 has emerged as an important mediator of fatty acid metabolism with paradoxical effects in the liver. Administration of IL-6 has been reported to confer protection against steatosis, but plasma and tissue IL-6 concentrations are elevated in chronic liver diseases, including fatty liver diseases associated with obesity and alcoholic ingestion. In this study, we further investigated the role of IL-6 on steatosis induced through a high-fat diet (HFD in wild-type (WT and IL-6-deficient (IL-6−/− mice. Additionally, HFD-fed IL-6−/− mice were also chronically treated with recombinant IL-6 (rIL-6. Obesity in WT mice fed a HFD associated with elevated serum IL-6 levels, fatty liver, upregulation of carnitine palmitoyltransferase 1 (CPT1 and signal transducer and activator of transcription-3 (STAT3, increased AMP kinase phosphorylation (p-AMPK, and downregulation of the hepatic lipogenic enzymes fatty acid synthase (FAS and stearoyl-CoA desaturase 1 (SCD1. The HFD-fed IL-6−/− mice showed severe steatosis, no changes in CPT1 levels or AMPK activity, no increase in STAT3 amounts, inactivated STAT3, and marked downregulation of the expression of acetyl-CoA carboxylase (ACCα/β, FAS and SCD1. The IL-6 chronic replacement in HFD-fed IL-6−/− mice restored hepatic STAT3 and AMPK activation but also increased the expression of the lipogenic enzymes ACCα/β, FAS and SCD1. Furthermore, rIL-6 administration was associated with aggravated steatosis and elevated fat content in the liver. We conclude that, in the context of HFD-induced obesity, the administration of rIL-6 might contribute to the aggravation of fatty liver disease through increasing lipogenesis.

  17. High pressure measurement and CPA equation of state for solubility of carbon dioxide and hydrogen sulfide in 1-butyl-3-methylimidazolium acetate

    International Nuclear Information System (INIS)

    Haghtalab, Ali; Kheiri, Alireza

    2015-01-01

    Highlights: • Solubility of carbon dioxide in pure [bmim][acetate] is measured. • Simultaneous solubility of CO 2 + H 2 S in [bmim][acetate] is measured. • Both physical and chemical models are applied to modelling the (acid gas + IL) systems. • The CPA EoS is used for phase equilibrium calculation. • A reaction thermodynamic equilibrium model is used in liquid phase. - Abstract: Removal of acid gases such as CO 2 and H 2 S from natural gas is essential for commercial, safety and environmental protection that demonstrate the importance of gas sweetening process. Ionic liquids (IL) have been highly demanded as a green solvent to remove acid gases from sour natural gas and capturing of CO 2 from flue gases. In this work, the solubility of CO 2 in 1-butyl-3-methylimidazolium acetate ([bmim][Ac]) is measured at temperatures (303.15, 328.15, 343.15) K and pressure range of (0.1 to 3.9) MPa. Moreover, the experiments are carried out for simultaneous measurements of (CO 2 + H 2 S) (70% + 30% on a mole basis) solubility in the same ionic liquid at T = (303.15, 323.15, 343.15) K and a pressure range of (0.1 to 2.2) MPa. To model the solubility of acid gases in IL, both physical and chemical equilibria are applied so that the (vapour + liquid) equilibrium calculation is carried out through Cubic-Plus-Association (CPA) EoS. The reaction equilibrium thermodynamic model is used in liquid phase so that the chemical reaction is taking place between IL and acid gasses. The Henry’s and reaction equilibrium constants are obtained though optimization of the solubility data. Using CPA EOS, the pure parameters of [bmim][acetate] are optimised and consequently using these parameters, gas partial pressure calculation is performed for the (CO 2 + IL) and (CO 2 + H 2 S + IL) systems. For the (CO 2 + IL) system, the percent average absolute deviation (AAD%) of 4.83 is resulted and for the (H 2 S + CO 2 + IL) system the values of 18.8 and 13.7 are obtained for H 2 S and CO 2

  18. Evaluation of IL-4, IL-17, and IFN-γ Levels in PatientsWith Breast Cancer

    Directory of Open Access Journals (Sweden)

    Mina Rohani Borj

    2017-03-01

    Full Text Available Introduction: Tumor growth depends on intrinsic properties of malignant tumor and tumor microenvironment. Cytokines are secreted substances of the tumor microenvironment which are widely produced by tumor and immune cells. The aim of this research was to evaluate concentrations of interleukin 4 (IL-4, interleukin 7 (IL-17 and interferon gamma (IFN-γ in the breast cancer microenvironment. Methods: One hundred sixteen women between 18-73 years of age (61.15 ± 24.39 were enrolled in this study. Based on pathologic diagnostic assessment, patients were divided into 2 categories: those affected with benign breast tumor, and the subjects suffering from malignant breast tumors. Biopsy specimens were collected. Following homogenization, IFN-γ, IL-17, and IL-4 concentrations were determined in tumor tissues, adjacent tissues of the tumor, and blood serum samples of these 2 groups of patients by enzyme-linked immunosorbent assay (ELISA method. Results: Concentrations of IFN-γ, IL-17, and IL-4 were measured in tumor tissue samples, adjacent tissues of the tumor, and blood serum samples in both groups. Malignant breast tumor samples had significantly higher concentrations of IL-4 and IL-17 compared with benign breast tumor samples. And also the concentration of IFN-γ in adjacent tissues of the tumor and in blood serums in patients with malignant breast tumors was significantly higher than that in the benign breast tumor samples. However, there was no significant difference between the concentration of IFN-γ in neoplastic breast tumor tissues and that in the benign breast tumor tissues (P > 0. 05. Conclusion: Our data indicated that IL-17 and IL-4 cytokines but not IFN-γ had higher concentrations in the subjects with malignant tumor compared with those with benign tumor. The present findings indicated that the concentrations of IL-4 and IL-17 in tumor tissues may be associated with the severity of breast malignancy.

  19. Transcriptional profiling of human familial longevity indicates a role for ASF1A and IL7R.

    Directory of Open Access Journals (Sweden)

    Willemijn M Passtoors

    Full Text Available The Leiden Longevity Study consists of families that express extended survival across generations, decreased morbidity in middle-age, and beneficial metabolic profiles. To identify which pathways drive this complex phenotype of familial longevity and healthy aging, we performed a genome-wide gene expression study within this cohort to screen for mRNAs whose expression changes with age and associates with longevity. We first compared gene expression profiles from whole blood samples between 50 nonagenarians and 50 middle-aged controls, resulting in identification of 2,953 probes that associated with age. Next, we determined which of these probes associated with longevity by comparing the offspring of the nonagenarians (50 subjects and the middle-aged controls. The expression of 360 probes was found to change differentially with age in members of the long-lived families. In a RT-qPCR replication experiment utilizing 312 controls, 332 offspring and 79 nonagenarians, we confirmed a nonagenarian specific expression profile for 21 genes out of 25 tested. Since only some of the offspring will have inherited the beneficial longevity profile from their long-lived parents, the contrast between offspring and controls is expected to be weak. Despite this dilution of the longevity effects, reduced expression levels of two genes, ASF1A and IL7R, involved in maintenance of chromatin structure and the immune system, associated with familial longevity already in middle-age. The size of this association increased when controls were compared to a subfraction of the offspring that had the highest probability to age healthily and become long-lived according to beneficial metabolic parameters. In conclusion, an "aging-signature" formed of 21 genes was identified, of which reduced expression of ASF1A and IL7R marked familial longevity already in middle-age. This indicates that expression changes of genes involved in metabolism, epigenetic control and immune function

  20. The effect of leptin, ghrelin, and neuropeptide-Y on serum Tnf-Α, Il-1β, Il-6, Fgf-2, galanin levels and oxidative stress in an experimental generalized convulsive seizure model.

    Science.gov (United States)

    Oztas, Berrin; Sahin, Deniz; Kir, Hale; Eraldemir, Fatma Ceyla; Musul, Mert; Kuskay, Sevinç; Ates, Nurbay

    2017-02-01

    The objective of this study is to examine the effects of the endogenous ligands leptin, ghrelin, and neuropeptide Y (NPY) on seizure generation, the oxidant/antioxidant balance, and cytokine levels, which are a result of immune response in a convulsive seizure model. With this goal, Wistar rats were divided into 5 groups-Group 1: Saline, Group 2: Saline+PTZ (65mg/kg), Group 3: leptin (4mg/kg)+PTZ, Group 4: ghrelin (80μg/kg)+PTZ, and Group 5: NPY (60μg/kg)+PTZ. All injections were delivered intraperitoneally, and simultaneous electroencephalography (EEG) records were obtained. Seizure activity was scored by observing seizure behavior, and the onset time, latency, and seizure duration were determined according to the EEG records. At the end of the experiments, blood samples were obtained in all groups to assess the serum TNF-α, IL-1β, IL-6, FGF-2, galanin, nitric oxide (NOֹ), malondialdehyde (MDA), and glutathione (GSH) levels. The electrophysiological and biochemical findings (p<0.05) of this study show that all three peptides have anticonvulsant effects in the pentylenetetrazol (PTZ)-induced generalized tonic-clonic convulsive seizure model. The reduction of the levels of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 caused by leptin, ghrelin, and NPY shows that these peptides may have anti-inflammatory effects in epileptic seizures. Also, leptin significantly increases the serum levels of the endogenous anticonvulsive agent galanin. The fact that each one of these endogenous peptides reduces the levels of MDA and increases the serum levels of GSH leads to the belief that they may have protective effects against oxidative damage that is thought to play a role in the pathogenesis of epilepsy. Our study contributes to the clarification of the role of these peptides in the brain in seizure-induced oxidative stress and immune system physiology and also presents new approaches to the etiology and treatment of tendency to epileptic seizures. Copyright

  1. The MHV68 M2 protein drives IL-10 dependent B cell proliferation and differentiation.

    Directory of Open Access Journals (Sweden)

    Andrea M Siegel

    2008-04-01

    Full Text Available Murine gammaherpesvirus 68 (MHV68 establishes long-term latency in memory B cells similar to the human gammaherpesvirus Epstein Barr Virus (EBV. EBV encodes an interleukin-10 (IL-10 homolog and modulates cellular IL-10 expression; however, the role of IL-10 in the establishment and/or maintenance of chronic EBV infection remains unclear. Notably, MHV68 does not encode an IL-10 homolog, but virus infection has been shown to result in elevated serum IL-10 levels in wild-type mice, and IL-10 deficiency results in decreased establishment of virus latency. Here we show that a unique MHV68 latency-associated gene product, the M2 protein, is required for the elevated serum IL-10 levels observed at 2 weeks post-infection. Furthermore, M2 protein expression in primary murine B cells drives high level IL-10 expression along with increased secretion of IL-2, IL-6, and MIP-1alpha. M2 expression was also shown to significantly augment LPS driven survival and proliferation of primary murine B cells. The latter was dependent on IL-10 expression as demonstrated by the failure of IL10-/- B cells to proliferate in response to M2 protein expression and rescue of M2-associated proliferation by addition of recombinant murine IL-10. M2 protein expression in primary B cells also led to upregulated surface expression of the high affinity IL-2 receptor (CD25 and the activation marker GL7, along with down-regulated surface expression of B220, MHC II, and sIgD. The cells retained CD19 and sIgG expression, suggesting differentiation to a pre-plasma memory B cell phenotype. These observations are consistent with previous analyses of M2-null MHV68 mutants that have suggested a role for the M2 protein in expansion and differentiation of MHV68 latently infected B cells-perhaps facilitating the establishment of virus latency in memory B cells. Thus, while the M2 protein is unique to MHV68, analysis of M2 function has revealed an important role for IL-10 in MHV68 pathogenesis

  2. The MHV68 M2 protein drives IL-10 dependent B cell proliferation and differentiation.

    Science.gov (United States)

    Siegel, Andrea M; Herskowitz, Jeremy H; Speck, Samuel H

    2008-04-04

    Murine gammaherpesvirus 68 (MHV68) establishes long-term latency in memory B cells similar to the human gammaherpesvirus Epstein Barr Virus (EBV). EBV encodes an interleukin-10 (IL-10) homolog and modulates cellular IL-10 expression; however, the role of IL-10 in the establishment and/or maintenance of chronic EBV infection remains unclear. Notably, MHV68 does not encode an IL-10 homolog, but virus infection has been shown to result in elevated serum IL-10 levels in wild-type mice, and IL-10 deficiency results in decreased establishment of virus latency. Here we show that a unique MHV68 latency-associated gene product, the M2 protein, is required for the elevated serum IL-10 levels observed at 2 weeks post-infection. Furthermore, M2 protein expression in primary murine B cells drives high level IL-10 expression along with increased secretion of IL-2, IL-6, and MIP-1alpha. M2 expression was also shown to significantly augment LPS driven survival and proliferation of primary murine B cells. The latter was dependent on IL-10 expression as demonstrated by the failure of IL10-/- B cells to proliferate in response to M2 protein expression and rescue of M2-associated proliferation by addition of recombinant murine IL-10. M2 protein expression in primary B cells also led to upregulated surface expression of the high affinity IL-2 receptor (CD25) and the activation marker GL7, along with down-regulated surface expression of B220, MHC II, and sIgD. The cells retained CD19 and sIgG expression, suggesting differentiation to a pre-plasma memory B cell phenotype. These observations are consistent with previous analyses of M2-null MHV68 mutants that have suggested a role for the M2 protein in expansion and differentiation of MHV68 latently infected B cells-perhaps facilitating the establishment of virus latency in memory B cells. Thus, while the M2 protein is unique to MHV68, analysis of M2 function has revealed an important role for IL-10 in MHV68 pathogenesis-identifying a

  3. Blocking IL-17A Alleviates Diabetic Retinopathy in Rodents.

    Science.gov (United States)

    Qiu, Ao-Wang; Liu, Qing-Huai; Wang, Jun-Ling

    2017-01-01

    Interleukin (IL)-17A, a proinflammatory cytokine, has been implicated in several autoimmune diseases. However, it is unclear whether IL-17A is involved in diabetic retinopathy (DR), one of the most serious complications of autoimmune diabetes. This study aimed to demonstrate that IL-17A exacerbates DR by affecting retinal Müller cell function. High glucose (HG)-treated rat Müller cell line (rMC-1) was exposed to IL-17A, anti-IL-17A-neutralizing monoclonal antibody (mAb) or/and anti-IL-17 receptor (R)A-neutralizing mAb for 24 h. For in vivo study, DR was induced by intraperitoneal injections of streptozotocin (STZ). DR model mice were treated with anti-IL-17A mAb or anti-IL-17RA mAb in the vitreous cavity. Mice that were prepared for retinal angiography were sacrificed two weeks after intravitreal injection, while the rest were sacrificed two days after intravitreal injection. IL-17A production and IL-17RA expression were increased in both HG-treated rMC-1 and DR retina. HG induced rMC-1 activation and dysfunction, as determined by the increased GFAP, VEGF and glutamate levels as well as the downregulated GS and EAAT1 expression. IL-17A exacerbated the HG-induced rMC-1 functional disorders, whereas either anti-IL-17A mAb or anti-IL-17RA mAb alleviated the HG-induced rMC-1 disorders. Intravitreal injections with anti-IL-17A mAb or anti-IL-17RA mAb in DR model mice reduced Müller cell dysfunction, vascular leukostasis, vascular leakage, tight junction protein downregulation and ganglion cell apoptosis in the retina. IL-17A aggravates DR-like pathology at least partly by impairing retinal Müller cell function. Blocking IL-17A is a potential therapeutic strategy for DR. © 2017 The Author(s)Published by S. Karger AG, Basel.

  4. The expression of GPR109A, NF-kB and IL-1β in peripheral blood leukocytes from patients with type 2 diabetes.

    Science.gov (United States)

    Liu, Fengxiu; Fu, Yucai; Wei, Chiju; Chen, Yongru; Ma, Shuhua; Xu, Wencan

    2014-01-01

    This study was designed to explore the association between the G protein-coupled receptor 109A (GPR109A) expression in peripheral blood leukocytes (PBLs) and type 2 diabetes (T2DM) and to discuss the regulation of inflammatory factors by GPR109A signaling. GPR109A signaling has been confirmed to be associated with homeostasis of glucose/lipid metabolism, but the role of signaling in T2DM is still poorly understood. Peripheral blood samples and biochemical data were collected from healthy individuals (normal controls) and T2DM patients. Immunocytochemical staining was used to detect the expression of GPR109A in PBLs. Reverse transcription polymerase chain reaction (RT-PCR) was used to measure mRNA levels of GPR109A, NF-κB, and IL-1β in PBLs. Immunocytochemical staining showed that the GPR109A protein is localized in the nucleus and cytoplasm of granulocytes, monocytes, and lymphocytes. RT-PCR showed that mRNA levels of GPR109A, NF-κB, and IL-1β were higher in the T2DM group than in the control group (P<0.05). Correlation analysis showed a positive correlation both between GPR109A/NF-κB (r=0.376, P<0.05), and GPR109A/IL-1β (r=501, P<0.05) and between GPR109A and fasting plasma glucose (FPG) (r=0.179, P<0.05) and NF-κB /FPG (r=0.358, p<0.05). Our results suggest that GPR109A signaling is associated with T2DM, playing a role in regulation of the inflammatory cytokines. © 2014 by the Association of Clinical Scientists, Inc.

  5. Duration and severity of symptoms and levels of plasma interleukin-1 receptor antagonist, soluble tumor necrosis factor receptor, and adhesion molecules in patients with common cold treated with zinc acetate.

    Science.gov (United States)

    Prasad, Ananda S; Beck, Frances W J; Bao, Bin; Snell, Diane; Fitzgerald, James T

    2008-03-15

    Zinc lozenges have been used for treatment of the common cold; however, the results remain controversial. Fifty ambulatory volunteers were recruited within 24 h of developing symptoms of the common cold for a randomized, double-blind, placebo-controlled trial of zinc. Participants took 1 lozenge containing 13.3 mg of zinc (as zinc acetate) or placebo every 2-3 h while awake. The subjective scores for common cold symptoms were recorded daily. Plasma zinc, soluble interleukin (IL)-1 receptor antagonist (sIL-1ra), soluble tumor necrosis factor receptor 1, soluble vascular endothelial cell adhesion molecule, and soluble intercellular adhesion molecule (sICAM)-1 were assayed on days 1 and 5. Compared with the placebo group, the zinc group had a shorter mean overall duration of cold (4.0 vs. 7.1 days; P cold symptoms. We related the improvement in cold symptoms to the antioxidant and anti-inflammatory properties of zinc.

  6. Serum TNF-α, IL-6 and Resistin Levels in Chronic Plaque Psoriasis

    Directory of Open Access Journals (Sweden)

    Yasemin Yıldırım

    2012-09-01

    Full Text Available Background and Design: Psoriasis is a chronic recurrent inflammatory disease of the skin. Despite previous extensive studies, etiology is still unclear. Obesity is a significant risk factor for psoriasis and body mass index (BMI correlates with the disease severity. In recent years, the relationship between psoriasis and adipose tissue cytokines has been reported. Therefore, in this study, we aimed to determine the levels of adipose tissue cytokines TNF-α, IL-6 and resistin in psoriasis patients and to evaluate their relation with disease severity.Material and Methods: Our study was performed between January 2010 and February 2010 on a total of 40 patients who were admitted to Abant Izzet Baysal University, Medical School Clinic of Dermatology with complaints of psoriasis. Additionally, forty healthy individuals whose age, gender and BMI did not differ from the patients’ ones formed the control group. TNF-α, IL-6, and resistin levels were measured in both the patients diagnosed with psoriasis and the control group using ELISA methods. The t-test and Mann-Whitney U test were performed to examine the differences between the two groups. Results: In our study, TNF-α, IL-6, and resistin levels were all significantly elevated in the patient group, and serum IL-6 and resistin correlated with disease severity. Psoriasis Area Severity Index (PASI score showed statistically significant association with IL-6 and resistin levels. Furthermore, it was detected that BMI did not correlate with serum TNF-α, IL-6, and resistin levels.Conclusion: The results of our study showed that TNF-α, IL-6, and resistin play a part in psoriasis etiopathogenesis, and IL-6 and resistin can be used as markers to assess the severity of the disease. Also, our study showed that the elevation in serum TNF-α, IL-6, and resistin levels is independent from the increase in adipose tissue. Larger studies are needed to support our findings.

  7. Seasonal influenza A/H3N2 virus infection and IL-1Β, IL-10, IL-17, and IL-28 polymorphisms in Iranian population.

    Science.gov (United States)

    Rogo, Lawal Dahiru; Rezaei, Farhad; Marashi, Seyed Mahdi; Yekaninejad, Mir Saeed; Naseri, Maryam; Ghavami, Nastaran; Mokhtari-Azad, Talat

    2016-12-01

    Increased blood cytokines is the main immunopathological process that were attributed to severe clinical outcomes in cases of influenza A/H3N2 virus infection. The study was aimed to investigate the polymorphisms of IL-1β, IL-10, IL-17, and IL-28 genes to find the possibility of their association with the clinical outcome of influenza A/H3N2 virus infection among the infected patients in Iran. This is a Case-Control study in which influenza A/H3N2 virus positive confirmed with real-time PCR were the cases. DNA samples from groups were genotyped for polymorphisms in rs16944 (IL-1β), rs1800872 (IL-10), rs2275913 (IL-17), and rs8099917 (IL-28). Confidence interval (95%CI) and Odds ratio (OR) were calculated. IL-17 rs2275913 (GG and AG) were associated with risk of infection with that were statistically significant (P rs16944) (GG) was associated with reduced risk of infection (P < 0.01, OR = 0.46). Genotype GG and GT of IL-10 (rs1800872) were associated with increased risk of infection with influenza A/H3N2 virus (P < 0.05, OR = 2.04-2.58). In addition, IL-28 (rs8099917) genotypes GG (P < 0.05, OR = 0.49) and TG (P < 0.05, OR = 0.59) were associated with reduced risk of ILI symptom while genotype TT (P < 0.01, OR = 4.31) was associated with increased risk of ILI symptom. The results of this study demonstrated that polymorphisms of genes involved in the inflammatory and anti-inflammatory process affect the outcome of disease caused by influenza A/H3N2 virus. Thorough insight on host immune response at the time of influenza A virus infection is required to ensure adequate patient care in the case of feature outbreaks. J. Med. Virol. 88:2078-2084, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Intestinal Epithelial Cell Tyrosine Kinase 2 Transduces IL-22 Signals To Protect from Acute Colitis.

    Science.gov (United States)

    Hainzl, Eva; Stockinger, Silvia; Rauch, Isabella; Heider, Susanne; Berry, David; Lassnig, Caroline; Schwab, Clarissa; Rosebrock, Felix; Milinovich, Gabriel; Schlederer, Michaela; Wagner, Michael; Schleper, Christa; Loy, Alexander; Urich, Tim; Kenner, Lukas; Han, Xiaonan; Decker, Thomas; Strobl, Birgit; Müller, Mathias

    2015-11-15

    In the intestinal tract, IL-22 activates STAT3 to promote intestinal epithelial cell (IEC) homeostasis and tissue healing. The mechanism has remained obscure, but we demonstrate that IL-22 acts via tyrosine kinase 2 (Tyk2), a member of the Jak family. Using a mouse model for colitis, we show that Tyk2 deficiency is associated with an altered composition of the gut microbiota and exacerbates inflammatory bowel disease. Colitic Tyk2(-/-) mice have less p-STAT3 in colon tissue and their IECs proliferate less efficiently. Tyk2-deficient primary IECs show reduced p-STAT3 in response to IL-22 stimulation, and expression of IL-22-STAT3 target genes is reduced in IECs from healthy and colitic Tyk2(-/-) mice. Experiments with conditional Tyk2(-/-) mice reveal that IEC-specific depletion of Tyk2 aggravates colitis. Disease symptoms can be alleviated by administering high doses of rIL-22-Fc, indicating that Tyk2 deficiency can be rescued via the IL-22 receptor complex. The pivotal function of Tyk2 in IL-22-dependent colitis was confirmed in Citrobacter rodentium-induced disease. Thus, Tyk2 protects against acute colitis in part by amplifying inflammation-induced epithelial IL-22 signaling to STAT3. Copyright © 2015 by The American Association of Immunologists, Inc.

  9. Issues concerning the determination of solubility products of sparingly soluble crystalline solids. Solubility of HfO{sub 2}(cr)

    Energy Technology Data Exchange (ETDEWEB)

    Rai, Dhanpat [Rai Enviro-Chem, LLC, Yachats, OR (United States); Kitamura, Akira [Japan Atomic Energy Agency, Ibaraki (Japan); Rosso, Kevin M. [Pacific Northwest National Laboratory, Richland, WA (United States); Sasaki, Takayuki; Kobayashi, Taishi [Kyoto Univ. (Japan)

    2016-11-01

    Solubility studies were conducted with HfO{sub 2}(cr) solid as a function HCl and ionic strength ranging from 2.0 to 0.004 mol kg{sup -1}. These studies involved (1) using two different amounts of the solid phase, (2) acid washing the bulk solid phase, (3) preheating the solid phase to 1400 C, and (4) heating amorphous HfO{sub 2}(am) suspensions to 90 C to ascertain whether the HfO{sub 2}(am) converts to HfO{sub 2}(cr) and to determine the solubility from the oversaturation direction. Based on the results of these treatments it is concluded that the HfO{sub 2}(cr) contains a small fraction of less crystalline, but not amorphous, material [HfO{sub 2}(lcr)] and this, rather than the HfO{sub 2}(cr), is the solubility-controlling phase in the range of experimental variables investigated in this study. The solubility data are interpreted using both the Pitzer and SIT models and they provide log{sub 10} K{sup 0} values of -(59.75±0.35) and -(59.48±0.41), respectively, for the solubility product of HfO{sub 2}(lcr)[HfO{sub 2}(lcr) + 2H{sub 2}O ↔ Hf{sup 4+} + 4OH{sup -}]. The log{sub 10} of the solubility product of HfO{sub 2}(cr) is estimated to be < -63. The observation of a small fraction of less crystalline higher solubility material is consistent with the general picture that mineral surfaces are often structurally and/or compositionally imperfect leading to a higher solubility than the bulk crystalline solid. This study stresses the urgent need, during interpretation of solubility data, of taking precautions to make certain that the observed solubility behavior for sparingly-soluble solids is assigned to the proper solid phase.

  10. Increased Interleukin-6 Activity Associated with Painful Chemotherapy-Induced Peripheral Neuropathy in Women after Breast Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Angela Starkweather

    2010-01-01

    Full Text Available Accumulating evidence suggests that neural-immune interactions are involved in the development of painful chemotherapy-induced peripheral neuropathy, particularly through the increased release of proinflammatory cytokines. The purpose of this study was used to evaluate levels of interleukin [IL]-6 and IL-6 receptors in women with breast cancer after the conclusion of chemotherapy who either had painful symptoms of chemotherapy-induced peripheral neuropathy (CIPN group, N=20 or did not experience CIPN symptoms (Comparison group, N=20. CIPN participants had significantly higher levels of IL-6 and soluble IL-6R (sIL-6R compared to women without CIPN symptoms (P<.001 for both. In addition, soluble gp130, which blocks the IL-6/sIL-6R complex from binding to gp130 within the cellular membrane, was significantly lower (P<.01. Circulating concentrations of sIL-6R were inversely correlated with the density of IL-6R on the cell surface of monocytes in the total sample (r=−.614,P=.005. These findings suggest that IL-6 transsignaling may be an important biological mechanism associated with the persistence of painful CIPN symptoms, with potential implications for symptom management and research.

  11. [Correlation of IL-8 and IL-6 in prostatic fluid with serum prostate-specific antigen level in patients with benign prostatic hyperplasia complicated by prostatitis].

    Science.gov (United States)

    Ren, Xingfei; Wu, Chunlei; Yu, Qinnan; Zhu, Feng; Liu, Pei; Zhang, Huiqing

    2016-01-01

    To investigate the correlation of the levels of interleukin-8 (IL-8) and IL-6 in the prostatic fluid with serum levels of serum prostate-specific antigen (PSA) in patients with benign prostatic hyperplasia (BPH) complicated by prostatitis. A series of 211 patients undergoing surgery of BPH were divided into BPH group (n=75) and BPH with prostatitis group (n=136) according to the white blood cell count in the prostatic fluid. The clinical and laboratory findings were compared between the two groups, and stepwise regression analysis was used to assess the association of IL-8 and IL-6 with serum PSA level. No significant differences were found in age, BMI, blood pressure, blood glucose, blood lipids, IPSS score, PSA-Ratio, or prostate volume between the two groups (Pprostatitis had significantly increased serum PSA and prostate fluid IL-8 and IL-6 levels compared with those without prostatitis (Pprostatic fluid were all positively correlated with serum PSA level. Prostatitis is an important risk factor for elevated serum PSA level in patients with BPH, and both IL-8 and IL-6 levels in the prostatic fluid are correlated with serum PSA level.

  12. IL-7 Enhances Thymic Human T Cell Development in "Human Immune System" Rag2-/-IL-2R{gamma}c-/- Mice without Affecting Peripheral T Cell Homeostasis

    NARCIS (Netherlands)

    van Lent, Anja U.; Dontje, Wendy; Nagasawa, Maho; Siamari, Rachida; Bakker, Arjen Q.; Pouw, Stephan M.; Maijoor, Kelly A.; Weijer, Kees; Cornelissen, Jan J.; Blom, Bianca; Di Santo, James P.; Spits, Hergen; Legrand, Nicolas

    2009-01-01

    IL-7 is a central cytokine in the development of hematopoietic cells, although interspecies discrepancies have been reported. By coculturing human postnatal thymus hematopoietic progenitors and OP9-huDL1 stromal cells, we found that murine IL-7 is approximately 100-fold less potent than human IL-7

  13. ST2 suppresses IL-6 production via the inhibition of IκB degradation induced by the LPS signal in THP-1 cells

    International Nuclear Information System (INIS)

    Takezako, Naoki; Hayakawa, Morisada; Hayakawa, Hiroko; Aoki, Shinsuke; Yanagisawa, Ken; Endo, Hitoshi; Tominaga, Shin-ichi

    2006-01-01

    LPS induces the production of inflammatory cytokines via the stimulation of Toll-like receptors. In this study, we demonstrated that a soluble secreted form of the ST2 gene product (ST2), a member of the interleukin-1 receptor family, suppressed the production of IL-6 in an LPS-stimulated human monocytic leukemia cell line, THP-1. Immunofluorescence confocal microscopy revealed the binding of ST2 to the surface of the THP-1 cells, in which ST2 led to decreased binding of nuclear factor-κB to the IL-6 promoter. Furthermore, the degradation of IκB in the cytoplasm after LPS stimulation was reduced by pretreatment with ST2. These results demonstrated that ST2 negatively regulates LPS-induced IL-6 production via the inhibition of IκB degradation in THP-1 cells

  14. Angiopoietin-2 and soluble Tie-2 receptor plasma levels in children with obstructive sleep apnea and obesity.

    Science.gov (United States)

    Gozal, David; Khalyfa, Abdelnaby; Qiao, Zhuanghong; Smith, Dale L; Philby, Mona F; Koren, Dorit; Kheirandish-Gozal, Leila

    2017-06-01

    Obstructive sleep apnea (OSA) is a prevalent condition, especially in children with obesity, and is associated with increased risk for metabolic syndrome (MetS). Angiopoietins have been identified as potential biomarkers of endothelial dysfunction and MetS. In adults, angiopoietin-2 (Ang-2) and its soluble receptor (sTie-2) are associated with diabetes, hypertension, and obesity and could be increased in children with OSA and obesity, particularly those with evidence of cardiometabolic alterations. One hundred twenty-six children (7.4 ± 2.0 years) were consecutively recruited and underwent overnight polysomnography, as well as endothelial function and BMI z score assessments and a fasting blood draw the morning after the sleep study. In addition to lipid profile, glucose and insulin levels, and homeostatic model assessment of insulin resistance (HOMA-IR), Ang-2 and sTie-2 concentrations were determined. Children with obesity and OSA had significantly elevated plasma Ang-2 and sTie-2 levels compared to corresponding controls with and without obesity. Furthermore, endothelial function (Tmax) and HOMA-IR were linearly and independently associated with Ang-2 and sTie-2 levels. In a small subset of children (n = 14), treatment of OSA by adenotonsillectomy resulted in reductions of Ang-2 and sTie-2 (P obesity, particularly when endothelial dysfunction or insulin resistance is detectable, and appear to decrease upon OSA treatment. © 2017 The Obesity Society.

  15. The SNP at −592 of human IL-10 gene is associated with serum IL-10 levels and increased risk for human papillomavirus cervical lesion development

    Directory of Open Access Journals (Sweden)

    Torres-Poveda Kirvis

    2012-11-01

    Full Text Available Abstract Background Women with Human Papilloma Virus (HPV persistence are characterized by high levels of IL-10 at cervix. We have determined whether polymorphisms of IL-10 gene promoter might be associated with increased risk of squamous intraepithelial cervical lesions (SICL and whether exist significative differences of IL-10 mRNA expression at cervix and systemic and serum IL-10 protein between SICL cases and non-Cervical Lesions (NCL. Methods Peripheral blood samples from SICL (n = 204 and NCL (n = 166 were used to detect IL-10 promoter polymorphisms at loci -592A/C (rs1800872, -819C/T (rs1800871, -1082A/G (rs1800896, -1352A/G (rs1800893, by allelic discrimination and to evaluate serum IL-10 protein. Cervical epithelial scrapings from NCL and biopsies from SICLs were used for HPV-typing and to evaluate IL-10 mRNA expression level. The systemic and local IL-10 mRNA expression levels were measured by real time-PCR. Genotypic and allelic frequencies of the selected polymorphisms were analyzed by logistic regression, adjusting by age and HPV-genotype, to determine the association with SICL. Results No significant differences were found between genotype frequencies at loci −819, -1082, and −1352. Individuals carrying at least one copy of risk allele A of polymorphism −592 had a two-fold increased risk of developing SICL [adjusted odds ratio (OR, 2.02 (95% CI, 1.26-3.25, p = 0.003], compared to NCL. The IL-10 mRNA expression and serum IL-10 protein, were significantly higher in SICL cases (p  Conclusions The −592 polymorphism is associated with increased risk of SICL and can serve as a marker of genetic susceptibility to SICL among Mexican women. According to IL-10 levels found in SICL, IL-10 can be relevant factor for viral persistence and progression disease.

  16. The Impact of MicroRNA-223-3p on IL-17 Receptor D Expression in Synovial Cells.

    Directory of Open Access Journals (Sweden)

    Nozomu Moriya

    Full Text Available Rheumatoid arthritis (RA is an autoimmune inflammatory disease affecting joints. Elevated plasma levels of microRNA-223-3p (miR-223-3p in patients with RA are implicated in the pathogenesis of the disease. This study aimed to analyze the functional role of miR-223-3p in the pathogenesis of RA by overexpressing miR-223-3p in synovial cell lines.Arthritis was induced in the RA model of SKG mice by injection of ß-glucan. The histopathologic features of joints were examined using hematoxylin and eosin and immunohistochemical staining. Plasma levels of miRNA were determined by panel real-time PCR analysis. Target genes of the differentially expressed miRNAs in SKG mice were analyzed using miRNA target prediction algorithms. The dual-luciferase reporter system was used to evaluate the relationship between miR-223-3p and IL-17 receptor D (IL-17RD. The activity of miR-223-3p was analyzed by transfection of plasmid vectors overexpressing miR-223-3p into IL-17RD-expressing NIH3T3 and MH7A cell lines. Il6 and Il17rd mRNA expression was analyzed by quantitative real-time PCR. IL-17RD protein expression was analyzed by western blot analysis.We identified 17 upregulated miRNAs (fold change > 2.0 in plasma of SKG mice injected with ß-glucan relative to untreated SKG mice. Il17rd was identified as the candidate target gene of miR-223-3p using five miRNA target prediction algorithms. The transfection of plasmid vectors overexpressing miR-223-3p into NIH3T3 and MH7A cells resulted in the downregulation of Il17rd expression and upregulation of Il6 expression. Expression of miR-223-3p and Il6 mRNA in MH7A cells was upregulated; however, that of Il17rd mRNA was downregulated following TNF-α stimulation. IL-17RD expression in synovial tissues from SKG mice and RA patients was inversely correlated with the severity of arthritis.This study is the first to demonstrate that miR-223-3p downregulates IL-17RD in both mouse and human cells; miR-223-3p may contribute to

  17. Split2 Protein-Ligation Generates Active IL-6-Type Hyper-Cytokines from Inactive Precursors.

    Science.gov (United States)

    Moll, Jens M; Wehmöller, Melanie; Frank, Nils C; Homey, Lisa; Baran, Paul; Garbers, Christoph; Lamertz, Larissa; Axelrod, Jonathan H; Galun, Eithan; Mootz, Henning D; Scheller, Jürgen

    2017-12-15

    Trans-signaling of the major pro- and anti-inflammatory cytokines Interleukin (IL)-6 and IL-11 has the unique feature to virtually activate all cells of the body and is critically involved in chronic inflammation and regeneration. Hyper-IL-6 and Hyper-IL-11 are single chain designer trans-signaling cytokines, in which the cytokine and soluble receptor units are trapped in one complex via a flexible peptide linker. Albeit, Hyper-cytokines are essential tools to study trans-signaling in vitro and in vivo, the superior potency of these designer cytokines are accompanied by undesirable stress responses. To enable tailor-made generation of Hyper-cytokines, we developed inactive split-cytokine-precursors adapted for posttranslational reassembly by split-intein mediated protein trans-splicing (PTS). We identified cutting sites within IL-6 (E 134 /S 135 ) and IL-11 (G 116 /S 117 ) and obtained inactive split-Hyper-IL-6 and split-Hyper-IL-11 cytokine precursors. After fusion with split-inteins, PTS resulted in reconstitution of active Hyper-cytokines, which were efficiently secreted from transfected cells. Our strategy comprises the development of a background-free cytokine signaling system from reversibly inactivated precursor cytokines.

  18. A level-set method for two-phase flows with soluble surfactant

    Science.gov (United States)

    Xu, Jian-Jun; Shi, Weidong; Lai, Ming-Chih

    2018-01-01

    A level-set method is presented for solving two-phase flows with soluble surfactant. The Navier-Stokes equations are solved along with the bulk surfactant and the interfacial surfactant equations. In particular, the convection-diffusion equation for the bulk surfactant on the irregular moving domain is solved by using a level-set based diffusive-domain method. A conservation law for the total surfactant mass is derived, and a re-scaling procedure for the surfactant concentrations is proposed to compensate for the surfactant mass loss due to numerical diffusion. The whole numerical algorithm is easy for implementation. Several numerical simulations in 2D and 3D show the effects of surfactant solubility on drop dynamics under shear flow.

  19. Plasma uric acid levels correlate with inflammation and disease severity in Malian children with Plasmodium falciparum malaria.

    Directory of Open Access Journals (Sweden)

    Tatiana M Lopera-Mesa

    Full Text Available Plasmodium falciparum elicits host inflammatory responses that cause the symptoms and severe manifestations of malaria. One proposed mechanism involves formation of immunostimulatory uric acid (UA precipitates, which are released from sequestered schizonts into microvessels. Another involves hypoxanthine and xanthine, which accumulate in parasitized red blood cells (RBCs and may be converted by plasma xanthine oxidase to UA at schizont rupture. These two forms of 'parasite-derived' UA stimulate immune cells to produce inflammatory cytokines in vitro.We measured plasma levels of soluble UA and inflammatory cytokines and chemokines (IL-6, IL-10, sTNFRII, MCP-1, IL-8, TNFα, IP-10, IFNγ, GM-CSF, IL-1β in 470 Malian children presenting with uncomplicated malaria (UM, non-cerebral severe malaria (NCSM or cerebral malaria (CM. UA levels were elevated in children with NCSM (median 5.74 mg/dl, 1.21-fold increase, 95% CI 1.09-1.35, n = 23, p = 0.0007 and CM (median 5.69 mg/dl, 1.19-fold increase, 95% CI 0.97-1.41, n = 9, p = 0.0890 compared to those with UM (median 4.60 mg/dl, n = 438. In children with UM, parasite density and plasma creatinine levels correlated with UA levels. These UA levels correlated with the levels of seven cytokines [IL-6 (r = 0.259, p<0.00001, IL-10 (r = 0.242, p<0.00001, sTNFRII (r = 0.221, p<0.00001, MCP-1 (r = 0.220, p<0.00001, IL-8 (r = 0.147, p = 0.002, TNFα (r = 0.132, p = 0.006 and IP-10 (r = 0.120, p = 0.012]. In 39 children, UA levels were 1.49-fold (95% CI 1.34-1.65; p<0.0001 higher during their malaria episode [geometric mean titer (GMT 4.67 mg/dl] than when they were previously healthy and aparasitemic (GMT 3.14 mg/dl.Elevated UA levels may contribute to the pathogenesis of P. falciparum malaria by activating immune cells to produce inflammatory cytokines. While this study cannot identify the cause of elevated UA levels, their association with parasite density and creatinine levels suggest that parasite-derived UA

  20. Low prevalence of antibodies and other plasma factors binding to CC chemokines and IL-2 in HIV-positive patients

    DEFF Research Database (Denmark)

    Meyer, C N; Svenson, M; Schade Larsen, C

    2000-01-01

    of HIV-infected patients were therefore assessed by radioimmunoassay and radioreceptor assay. IgG from 4/505 HIV patients and 9/2000 healthy controls (p>0.05) bound rMIP-1alpha and rMIP-1beta, but not rRANTES. No other plasma factors bound the chemokines. The antibodies inhibited receptor binding of both...... chemokines. There was no association between presence of antibodies and disease stage or HIV progression rate. Three of 11 patients treated with rIL-2 developed IgG antibodies suppressing cellular binding and growth promotion of rIL-2. Hence, circulating factors, including antibodies MIP-1alpha/MIP-1beta...

  1. Correlation between IL-10 and microRNA-187 expression in epileptic rat hippocampus and patients with temporal lobe epilepsy

    Directory of Open Access Journals (Sweden)

    Walid A. Alsharafi

    2015-12-01

    Full Text Available Accumulating evidence is emerging that microRNAs (miRs are key regulators controlling neuroinflammatory processes, which are known to play a potential role in the pathogenesis of temporal lobe epilepsy (TLE. The aim of the present study was to investigate the dynamic expression pattern of interleukin (IL–10 as an anti-inflammatory cytokine and miR-187 and post-transcriptional inflammation-related miRNA in the hippocampus of a rat model of status epilepticus (SE and patients with TLE. We performed a real-time quantitative PCR and western blot on rat hippocampus (2 hours, 7 days, 21 days and 60 days following pilocarpine-induced SE, and on hippocampus obtained from TLE patients and normal controls. To detect the relationship between IL-10 and miR-187 on neurons, lipopolysaccharide (LPS and IL-10-stimulated neurons were prepared. Furthermore, we identified the effect of antagonizing of miR-187 by its antagomir on IL-10 secretion. Here we reported that that IL-10 secretion and miR-187 expression levels are inversely correlated after SE.. In patients with TLE, the expression levels of IL-10 was also significantly upregulated, whereas miR-187 expression was significantly downregulated. Moreover, miR-187 expression was significantly reduced following IL-10 stimulation in an IL-10–dependent manner. On the other hand, antagonizing miR-187 reduced the production of IL-10 in hippocampal tissues of rat model of SE. Our findings demonstrate a critical role of miR-187 in the physiological regulation of IL-10 anti-inflammatory responses and elucidate the role of neuro-inflammation in the pathogenesis of TLE. Therefore, modulation of the IL-10 / miR-187 axis may be a new therapeutic approach for TLE.

  2. Clinical significance of determination of serum L-2, SL-2R and TNF-α levels in patients with diabetic-2 nephrosis

    International Nuclear Information System (INIS)

    Wang Jinsong

    2007-01-01

    Objective: To investigate the clinical significance of changes of serum L-2, SL-2R and TNF-α were significantly higher -α levels in patients with diabetic-2 nephrosis. Methods: Serum L-2, TNF 2R (with ELISA) levels in 42 patients with diabetic-2 nephrosis were measured, and 35 controls. Results: Serum levels of SL-2R and TNF-α were significantly higher in patients with diabetic-2 nephrosis than those in controls (P < 0.01), but serum L-2 levels were significantly lower in the patients (P < 0.01). Conclusion: These cytokines participated in the pathogenesis of diabetic-2 nephrosis and monitoring the changes of their serum levels was helpful to the management of the diseases. (authors)

  3. Decreased IL-33 Production Contributes to Trophoblast Cell Dysfunction in Pregnancies with Preeclampsia

    Directory of Open Access Journals (Sweden)

    Hong Chen

    2018-01-01

    Full Text Available Preeclampsia (PE is a life-threatening pregnancy complication which is related to aggradation of risk regarding fetal and maternal morbidity and mortality. Dysregulation of systemic inflammatory response and dysfunction of trophoblast cells have been proposed to be involved in the development and progression of PE. Some studies have demonstrated that interleukin-33 (IL-33 is an immunomodulatory cytokine that is associated with the immune regulation of tumor cells. However, little is known whether IL-33 and its receptor ST2/IL-1 R4 could regulate trophoblast cells, which are associated with the pathogenesis of PE. In this study, our target is to explore the impact of IL-33 on trophoblast cells and elucidate its underlying pathophysiological mechanisms. Placental tissues from the severe PE group (n=11 and the normotensive pregnant women’s group (n=11 were collected for the protein expression and distribution of IL-33 along with its receptor ST2/IL-1 R4 via Western blot analysis and immunohistochemistry, respectively. We discovered that the level of IL-33 was decreased in placental tissues of pregnant women with PE, while no distinction was observed in the expression of ST2/IL-1 R4. These results were further verified in villous explants which were treated with sodium nitroprusside with different concentrations, to simulate the pathological environment of PE. To investigate IL-33 effects on trophoblast cells separately, IL-33 shRNA was introduced into HTR8/SVneo cells and villi. IL-33 shRNA weakened the proliferation, migration, and invasion capacity of HTR8/SVneo cells. The migration distance of villous explants was also markedly decreased. The reduced invasion of trophoblast cells is a result of IL-33 knockdown which could be related to the decline of MMP2/9 activity and the increased utterance of TIMP1/2. Overall, our findings demonstrated that the reduction of IL-33 production was connected with the reduced functional capability of

  4. IL-2 absorption affects IFN-gamma and IL-5, but not IL-4 producing memory T cells in double color cytokine ELISPOT assays.

    Science.gov (United States)

    Quast, Stefan; Zhang, Wenji; Shive, Carey; Kovalovski, Damian; Ott, Patrick A; Herzog, Bernhard A; Boehm, Bernhard O; Tary-Lehmann, Magdalena; Karulin, Alexey Y; Lehmann, Paul V

    2005-09-01

    Cytokine assays are gaining increasing importance for human immune monitoring because they reliably detect antigen-specific T cells in primary PBMC, even at low clonal sizes. Double color ELISPOT assays permit the simultaneous visualization of cells producing two different cytokines. Permitting the simultaneous assessment of type 1 and 2 immunity and due to the limited numbers of PBMC available from human study subjects, double color assays should be particularly attractive for clinical trials. Since the performance of double color assays has not yet been validated, we set out to compare them to single color measurements. Testing the recall antigen-induced cytokine response of PBMC, we found that double color assays regularly provided lower numbers of IFN-gamma and IL-5 spots than single color measurements when IL-2 detection was part of the double color assay. We showed that the inhibitory effect resulted from IL-2 absorption and could be overcome by either antibody free preactivation cultures or by inclusion of anti-CD28 antibody. In contrast, the simultaneous detection of IL-2 did not affect the numbers of IL-4 spots. Therefore, unlike IL-2/IL-4 and IFN-gamma/IL-5 assays, IL-2/IFN-gamma, and IL-2/IL-5 assays require compensation for the IL-2 capture to provide accurate numbers for the frequencies of cytokine producing memory T cells.

  5. Measurement of biologically active interleukin-1 by a soluble receptor binding assay

    International Nuclear Information System (INIS)

    Riske, F.; Chizzonite, R.; Nunes, P.; Stern, A.S.

    1990-01-01

    A soluble receptor binding assay has been developed for measuring human interleukin-1 alpha (IL-1 alpha), human IL-1 beta, and mouse IL-1 alpha. The assay is based on a competition between unlabeled IL-1 and 125I-labeled mouse recombinant IL-1 alpha for binding to soluble IL-1 receptor prepared from mouse EL-4 cells. The assay measures only biologically active IL-1 folded in its native conformation. The ratio of human IL-1 alpha to human IL-1 beta can be measured in the same sample by a pretreatment step which removes human IL-1 beta from samples prior to assay. This technique has been used to monitor the purification of recombinant IL-1, and may be utilized to specifically and accurately measure bioactive IL-1 in human serum and cell culture supernatants

  6. Microvascular abnormalities in capillaroscopy correlate with higher serum IL-18 and sE-selectin levels in patients with type 1 diabetes complicated by microangiopathy

    Directory of Open Access Journals (Sweden)

    Maria Górska

    2011-04-01

    Full Text Available Microvascular abnormalities are one of the most important causes of persistent diabetic complications. The aim of this study was to compare microvascular changes examined by nailfold capillaroscopy with serum concentrations of soluble E-selectin (sE-selectin and IL-18 in type 1 diabetic patients with and without microangiopathy. Serum levels of sE-selectin and IL-18 were determined by an enzyme-linked immunosorbent assay in 106 patients with type 1 diabetes and in 40 healthy controls. All diabetic patients were evaluated by extensive clinical, laboratory and capillaroscopic studies. Morphological changes were observed by nailfold capillaroscopy in 86 out of 106 (81% diabetic patients. Severe capillaroscopic changes were seen in 32 out of 54 (59% patients with microangiopathy, but in only seven out of 52 (13% patients without microangiopathy. Higher serum levels of sE-selectin (p < 0.001 and IL-18 (p < 0.05 were demonstrated in diabetic patients compared to controls. Significant differences of sE-selectin (p < 0.001 and IL-18 (p < 0.01 serum concentrations were observed between diabetic patients with microangiopathy and controls. Moreover, comparison between patients with and without microangiopathic complications showed a significantly higher capillaroscopic score and sE-selectin serum concentration in the group with microangiopathy (p < 0.001. Furthermore, diabetic patients with severe microvascular changes in capillaroscopy showed significantly higher IL-18 (p < 0.001 and sE-selectin (p < 0.05 serum levels than subgroups without changes or with mild abnormalities. Our findings suggest that abnormalities in nailfold capillaroscopy may reflect the extent of microvascular involvement and are associated with higher sE-selectin and IL-18 serum levels, as well as with microangiopathic complications in diabetic patients. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 1, pp. 104–110

  7. Comparative analysis of the lambda-interferons IL-28A and IL-29 regarding their transcriptome and their antiviral properties against hepatitis C virus.

    Directory of Open Access Journals (Sweden)

    Julia Diegelmann

    Full Text Available BACKGROUND: Specific differences in signaling and antiviral properties between the different Lambda-interferons, a novel group of interferons composed of IL-28A, IL-28B and IL-29, are currently unknown. This is the first study comparatively investigating the transcriptome and the antiviral properties of the Lambda-interferons IL-28A and IL-29. METHODOLOGY/PRINCIPAL FINDINGS: Expression studies were performed by microarray analysis, quantitative PCR (qPCR, reporter gene assays and immunoluminometric assays. Signaling was analyzed by Western blot. HCV replication was measured in Huh-7 cells expressing subgenomic HCV replicon. All hepatic cell lines investigated as well as primary hepatocytes expressed both IFN-λ receptor subunits IL-10R2 and IFN-λR1. Both, IL-28A and IL-29 activated STAT1 signaling. As revealed by microarray analysis, similar genes were induced by both cytokines in Huh-7 cells (IL-28A: 117 genes; IL-29: 111 genes, many of them playing a role in antiviral immunity. However, only IL-28A was able to significantly down-regulate gene expression (n = 272 down-regulated genes. Both cytokines significantly decreased HCV replication in Huh-7 cells. In comparison to liver biopsies of patients with non-viral liver disease, liver biopsies of patients with HCV showed significantly increased mRNA expression of IL-28A and IL-29. Moreover, IL-28A serum protein levels were elevated in HCV patients. In a murine model of viral hepatitis, IL-28 expression was significantly increased. CONCLUSIONS/SIGNIFICANCE: IL-28A and IL-29 are up-regulated in HCV patients and are similarly effective in inducing antiviral genes and inhibiting HCV replication. In contrast to IL-29, IL-28A is a potent gene repressor. Both IFN-λs may have therapeutic potential in the treatment of chronic HCV.

  8. Genetic regulation ofmethylation and IL1RL1-a protein levels in asthma

    NARCIS (Netherlands)

    Dijk, F Nicole; Xu, Chengjian; Melén, Erik; Carsin, Anne-Elie; Kumar, Asish; Nolte, Ilja M; Gruzieva, Olena; Pershagen, Goran; Grotenboer, Neomi S; Savenije, Olga E M; Antó, Josep Maria; Lavi, Iris; Dobaño, Carlota; Bousquet, Jean; van der Vlies, Pieter; van der Valk, Ralf J P; de Jongste, Johan C; Nawijn, Martijn C; Guerra, Stefano; Postma, Dirkje S; Koppelman, Gerard H

    2018-01-01

    Interleukin-1 receptor-like 1 (IL1RL1) is an important asthma gene. (Epi)genetic regulation ofIL1RL1protein expression has not been established. We assessed the association betweenIL1RL1single nucleotide polymorphisms (SNPs),IL1RL1methylation and serum IL1RL1-a protein levels, and aimed to identify

  9. 25-Hydroxyvitamin D, IL-31, and IL-33 in Children with Allergic Disease of the Airways

    Directory of Open Access Journals (Sweden)

    Anna Bonanno

    2014-01-01

    Full Text Available Low vitamin D is involved in allergic asthma and rhinitis. IL-31 and IL-33 correlate with Th2-associated cytokines in allergic disease. We investigated whether low vitamin D is linked with circulating IL-31 and IL-33 in children with allergic disease of the airways. 25-Hydroxyvitamin D [25(OH Vit D], IL-31, and IL-33 plasma levels were measured in 28 controls (HC, 11 allergic rhinitis (AR patients, and 35 allergic asthma with rhinitis (AAR patients. We found significant lower levels of 25(OH Vit D in AR and in AAR than in HC. IL-31 and IL-33 plasma levels significantly increased in AAR than HC. IL-31 and IL-33 positively correlated in AR and AAR. 25(OH Vit D deficient AAR had higher levels of blood eosinophils, exacerbations, disease duration, and total IgE than patients with insufficient or sufficient 25(OH Vit D. In AAR 25(OH Vit D levels inversely correlated with total allergen sIgE score and total atopy index. IL-31 and IL-33 did not correlate with 25(OH Vit D in AR and AAR. In conclusion, low levels of 25(OH Vit D might represent a risk factor for the development of concomitant asthma and rhinitis in children with allergic disease of the airways independently of IL-31/IL-33 Th2 activity.

  10. Changes of serum procalcitonin (PCT) and IL-6 levels in patients with sepsis

    International Nuclear Information System (INIS)

    Wang Jinjiang

    2007-01-01

    Objective: To investigate the importance of determination of changes of serum procalcitonin (PCT) and IL-6 levels in patients with sepsis. Methods: Serum PCT (with double-sandwich immunofluorescence assay) and IL-6 (with ELISA) levels were measured repeatedly in 130 patients with sepsis on d1, d3, d5, d7 after admission. Values in 130 healthy individuals were also measured as control. Results: The serum levels of PCT and IL-6 in the patients with sepsis of admission were significantly higher than those in controls. The levels dropped markedly in the survivors by d7. Among the septic patients, the levels in the succumbed patients were significantly higher those in the survivors (P<0.05). Conclusion: Serum PCT and IL-6 values appeared to be of prognostic value in patients with sepsis. (authors)

  11. Fish oil affects immune function in 9 to 12 month old infants

    DEFF Research Database (Denmark)

    Damsgaard, Camilla Trab; Lauritzen, Lotte; Kjær, Tanja

    2006-01-01

    /day) or no fish oil and cow’s milk or infant formula from 9 to 12 month of age in 64 healthy Danish infants. Before and after the intervention we measured the fatty acid composition of erythrocyte (RBC) membranes, plasma IgE levels, C-reactive protein and soluble IL-2 receptors (sIL-2R) as well as cytokine...

  12. Carbon monoxide releasing molecule-2 ameliorates IL-1β-induced IL-8 in human gastric cancer cells

    International Nuclear Information System (INIS)

    Lian, Sen; Xia, Yong; Ung, Trong Thuan; Khoi, Pham Ngoc; Yoon, Hyun Joong; Kim, Nam Ho; Kim, Kyung Keun; Jung, Young Do

    2016-01-01

    Carbon monoxide (CO), a byproduct of heme oxygenase (HO), presents antioxidant, anti-inflammatory, and anti-tumor properties. Accumulating evidence supports that interleukin (IL)-8 contribute to the vascularity of human gastric cancer. However, the inhibition of IL-8 expression by CO is yet to be elucidated. Here, we utilized CO releasing molecule-2 (CORM-2) to investigate the effect of CO on IL-1β-induced IL-8 expression and the underlying molecular mechanisms in human gastric cancer AGS cells. CORM-2 dose-dependently suppressed IL-1β-induced IL-8 mRNA and protein expression as well as IL-8 promoter activity. IL-1β induced the translocation of p47 phox to activate reactive oxygen species (ROS)-producing NADPH oxidase (NOX). Moreover, IL-1β activated MAPKs (Erk1/2, JNK1/2, and p38 MAPK) and promoted nuclear factor (NF)-kB and activator protein (AP)-1 binding activities. Pharmacological inhibition and mutagenesis studies indicated that NOX, ROS, Erk1/2, and p38 MAPK are involved in IL-1β-induced IL-8 expression. Transient transfection of deletion mutant constructs of the IL-8 promoter in cells suggested that NF-kB and AP-1 are critical for IL-1β-induced IL-8 transcription. NOX-derived ROS and MAPKs (Erk1/2 and p38 MAPK) functioned as upstream activators of NF-κB and AP-1, respectively. CORM-2 pretreatment significantly mitigated IL-1β-induced activation of ROS/NF-kB and Erk1/2/AP-1 cascades, blocking IL-8 expression and thus significantly reducing endothelial cell proliferation in the tumor microenvironment.

  13. Changes in serum interleukin-6, C-reactive protein and thrombomodulin levels under periodontal ultrasonic debridement.

    Science.gov (United States)

    Ushida, Yuka; Koshy, Geena; Kawashima, Yoko; Kiji, Makoto; Umeda, Makoto; Nitta, Hiroshi; Nagasawa, Toshiyuki; Ishikawa, Isao; Izumi, Yuichi

    2008-11-01

    This study aimed to compare the effect of single-visit full-mouth mechanical debridement (FMD) and quadrant-wise mechanical debridement (QMD) on the levels of serum interleukin (IL)-6, C-reactive protein (CRP) and soluble thrombomodulin. Thirty-six subjects with chronic periodontitis were randomly allocated to three groups: undergoing QMD, single-visit FMD with povidone iodine or with water. Serum IL-6 and soluble thrombomodulin were measured by enzyme-linked immunosorbent assay, and serum CRP was measured by the latex-enhanced nephelometric method. Serum IL-6 level increased significantly immediately after debridement in all the three groups, with this increase being greatest in the full-mouth groups. However, the increase in the full-mouth groups was not significantly higher than that of quadrant-wise group. In the quadrant-wise group, serum IL-6 level decreased significantly 1 month after debridement compared with baseline. Serum-soluble thrombomodulin decreased significantly in the full-mouth groups but not in the quadrant-wise group. Changes in CRP level were not significant at baseline or after debridement in all the three groups. FMD increased serum IL-6 and reduced serum-soluble thrombomodulin to a greater extent than QMD, suggesting that the former technique has stronger transient effects on systemic vascular endothelial functions than the latter.

  14. Vitamin D level and peculiarities of IFN-γ and IL-4 production in young children with recurrent broncho-obstructive syndrome

    Directory of Open Access Journals (Sweden)

    Yu.K. Bolbot

    2018-02-01

    0.05. API was negative in 78.3 % of patients of group II. The severe course of BOS was observed among children of group II two times more often than in group I (23.3 and 10.0 %, respectively, c2 = 4.50, p = 0.034. The mean of 25(OHD in the blood serum in children of group I was 33.0 (28.19; 41.97 ng/ml and group II — 13.68 (7.96; 19.51 ng/ml (p < 0.001. The level of VD in 75 % of children in group II was considered as deficiency while in group I this indicator was 6.6 % (c2 = 57.98, p < 0.001. The inverse correlation was found between VD level and the incidence (r = 0.27, p = 0.002 and severity of BOS (r = 0.24, p = 0.008. The level of total Ca in the blood serum in both groups was within the normal range. The mean level of IFN-g in children of group I was 22.69 (8.98; 41.44 pg/ml and in group II — 21.08 (8.57; 37.03 pg/ml, both of which were higher than in the control group (12.18 (5.31; 12.92 pg/ml (p = 0.016 for both parameters. We revealed that the study groups differed by the level of VD supplementation, which was 60 % in group I and only 5 % in children of group II (p < 0.001. The mean serum level of IL-4 in group I was significantly higher in comparison to the corresponding parameters of group II and control group (p = 0.012 according to the Mann-Whitney U test for both indicators. The inverse correlation between the incidence of BOS and IFN-g level in the blood was found in children of group I (r = –0.45, p < 0.001, and between severity of BOS and the serum IL-4 concentration — in group II (r = –0.28, р = 0.030. Direct correlation between IL-4 and IFN-g (r = 0.41, p < 0.001 was revealed in patients with recurrent BOS. No correlation between VD and immunological indicators was found. Conclusions. BOS has predominantly viral etiology in young children. The severe course of the disease is more common in children with recurrent episodes of BOS although most of them have negative asthma predictive index. In 3/4 of patients with recurrent BOS, the

  15. Decreased placental and maternal serum TRAIL-R2 levels are associated with placenta accreta.

    Science.gov (United States)

    Oztas, Efser; Ozler, Sibel; Ersoy, Ali Ozgur; Ersoy, Ebru; Caglar, Ali Turhan; Uygur, Dilek; Yucel, Aykan; Ergin, Merve; Danisman, Nuri

    2016-03-01

    TNF-related apoptosis-inducing ligand receptor-2 (TRAIL-R2) is produced both by decidual and trophoblast cells during pregnancy and known to participate in apoptosis. In this study, we aimed to determine and to compare maternal serum and placental TRAIL-R2 levels in patients with placenta accreta, non-adherent placenta previa and in healthy pregnancies. We also aimed to analyze the association of placenta accreta with the occurrence of previous C-sections. A total of 82 pregnant women were enrolled in this case-control study (27 placenta accreta patients, 26 non-adherent placenta previa patients and 29 age-, and BMI-matched healthy, uncomplicated pregnant controls). TRAIL-R2 levels were studied in both maternal serum and placental tissue homogenates. Determining the best predictor(s) which discriminate placenta accreta was analyzed by multiple logistic regression analyses. Adjusted odds ratios and 95% confidence intervals were also calculated. Both placental and serum TRAIL-R2 levels were significantly lower in placenta accreta group (median 34.82 pg/mg and 19.85 pg/mL, respectively) when compared with both non-adherent placenta previa (median 39.24 pg/mg and 25.99 pg/mL, respectively) and the control groups (median 41.62 pg/mg and 25.87 pg/mL, respectively) (p Placental TRAIL-R2 levels and previous cesarean section were found to be significantly associated with placenta accreta (OR: 0.934 95% CI 0.883-0.987, p = 0.016 and OR:7.725 95% CI: 2.717-21.965, p Placental and serum TRAIL-R2 levels were positively correlated. Decreased levels of placental TRAIL-R2 and previous history of cesarean section were found to be significantly associated with placenta accreta, suggesting a possible role of apoptosis in abnormal trophoblast invasion. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Expression of fusion IL2-B7.1(IgV+C) and effects on T lymphocytes.

    Science.gov (United States)

    Kong, Linghong; Li, Yaochen; Yang, Ye; Li, Kangsheng

    2007-12-01

    The search for an effective immunotherapeutic treatment for tumors is an important area of cancer research. To prepare a more effective form of the bifunctional fusion protein IL2-B7.1(IgV+C) and analyze its effect on the stimulation of T lymphocyte proliferation, we used DNAStar 5.03 software to predict the structural diversity and biochemical character of IL2-B7.1(IgV+C). We then prepared fusion protein IL2-B7.1(IgV+C) by establishing its prokaryotic expression system, and tested its effect on the stimulation of T lymphocytes in vitro. The results indicated that IL2-B7.1(IgV+C) correctly formed a secondary structure in which both IL2 and B7.1(IgV+C) maintained their original hydrophilicity and epitopes. Western blot analysis revealed that IL2-B7.1(IgV+C) was efficiently expressed. Our analysis of CTLL-2 and T-cell proliferation showed that recombinant human (rh) IL2-B7.1(IgV+C) exerted the combined stimulating effects of both rhIL2 and rh B7.1(IgV+C) on cell proliferation, and that these effects could be blocked by adding either anti-IL2 or anti-B7.1 monoclonal antibodies. A >2-fold increase in [3H]TdR incorporation compared with that of cells treated with recombinant protein IL2, or B7.1(IgV+C) alone, revealed that rhIL2-B7.1(IgV+C) had dose-dependent synergetic effects on T-cell activation in the presence of anti-CD3 monoclonal antibody. We concluded that the augmented potency of rhIL2-B7.1(IgV+C) resulted in a stronger stimulation of T-cell proliferation than either rhB7.1(IgV+C) or rhIL2 alone.

  17. Effect of flurbiprofen aretilon on serum hs-CRP, IL-6 levels in patients undergoing esophageal cancer surgery

    International Nuclear Information System (INIS)

    Li Jiakai

    2011-01-01

    Objective: To investigate the effect of flurbiprofen axetil on serum high sensitivity C reactive protein (hs-CRP) and interleukin-6 (IL-6) in the patients undergoing esophageal cancer surgery. Methods: Thirty patients were divided into 2 groups with 15 cases each. The patients in groups A were given flurbiprofen axetil and those in group B were not as the controls. Serum hs-CRP (immuno-turbidity method) and IL-6 (RIA) levels were determined before anesthesia induction and after extubation. Results: The levels of serum hs-CRP, IL-6 were significantly higher in group B than those in group A (P<0.05). Conclusion: Flurbiprofen axetil could reduce serum hs-CRP, IL-6 levels in patients undergoing Esophageal cancer surgery. (authors)

  18. Counterbalancing of TH2-driven allergic airway inflammation by IL-12 does not require IL-10.

    Science.gov (United States)

    Tournoy, K G; Kips, J C; Pauwels, R A

    2001-03-01

    Asthma is characterized by allergen-induced airway inflammation orchestrated by TH2 cells. The TH1-promoting cytokine IL-12 is capable of inhibiting the TH2-driven allergen-induced airway changes in mice and is therefore regarded as an interesting strategy for treating asthma. The antiallergic effects of IL-12 are only partially dependent of IFN-gamma. Because IL-12 is a potent inducer of the anti-inflammatory cytokine IL-10, the aim of the present study was to investigate in vivo whether the antiallergic effects of IL-12 are mediated through IL-10. C57BL/6J-IL-10 knock-out (IL-10(-/-)) mice were sensitized intraperitoneally to ovalbumin (OVA) and subsequently exposed from day 14 to day 21 to aerosolized OVA (1%). IL-12 was administered intraperitoneally during sensitization, subsequent OVA exposure, or both. IL-12 inhibited the OVA-induced airway eosinophilia, despite the absence of IL-10. Moreover, a shift from a TH2 inflammatory pattern toward a TH1 reaction was observed, with concomitant pronounced mononuclear peribronchial inflammation after IL-12 treatment. Allergen-specific IgE synthesis was completely suppressed only when IL-12 was administered along with the allergen sensitization. Furthermore, treating the animals with IL-12 at the time of the secondary allergen challenge resulted not only in a significant suppression of the airway responsiveness but also in an important IFN-gamma-associated toxicity. These results indicate that IL-12 is able to inhibit allergen-induced airway changes, even in the absence of IL-10. In addition, our results raise concerns regarding the redirection of TH2 inflammation by TH1-inducing therapies because treatment with IL-12 resulted not only in a disappearance of the TH2 inflammation but also in a TH1-driven inflammatory pulmonary pathology.

  19. Anti-Inflammatory Activity of Water-Soluble Polysaccharide of Agaricus blazei Murill on Ovariectomized Osteopenic Rats

    Directory of Open Access Journals (Sweden)

    Peng Wang

    2013-01-01

    Full Text Available In the present study, we investigated the anti-inflammatory activity of water-soluble polysaccharide of Agaricus blazei Murill (WSP-AbM on ovariectomized osteopenic rats. The rats were administered orally WSP-AbM (200 mg/kg BW for 8 weeks. Subsequent serum maleic dialdehyde (MDA level, total antioxidant status (TAOS, nuclear factor kappa B (NF-κB level, polymorphonuclear (PMN cells level, interleukin-1β (IL-1β level, inducible nitric oxide synthase (iNOS level, tumor necrosis factor-α (TNF-α level, adhesion molecule (ICAM-1, and cyclooxygenase-2 (COX-2 were determined by enzyme linked immunosorbent assay (ELISA and immunohistochemistry, respectively. WSP-AbM administration markedly (P<0.05 decreased serum IL-1β and TNF-α levels and the expressions of ICAM-1, COX-2, and iNOS NF-κB compared with OVX rats. WSP-AbM administration alsomarkedly (P<0.05 decreased PMN infiltration. In conclusion, we observed that WSP-AbM supplementation had anti-inflammatory effects in a model of osteoporosis disease.

  20. Inhibition of HIF-1α decreases expression of pro-inflammatory IL-6 and TNF-α in diabetic retinopathy.

    Science.gov (United States)

    Gao, Xiuhua; Li, Yonghua; Wang, Hongxia; Li, Chuanbao; Ding, Jianguang

    2017-12-01

    Recent studies demonstrate that pro-inflammatory cytokines (PICs, i.e. IL-1β, IL-6 and TNF-α) in retinal tissues are likely involved in the development of diabetic retinopathy (DR). In this report, we particularly examined contributions of hypoxia inducible factor subtype 1α (HIF-1α) to the expression of PICs and their receptors in diabetic retina. Streptozotocin (STZ) was systemically injected to induce hyperglycaemia in rats. ELISA and Western blot analysis were employed to determine the levels of HIF-1α and PICs as well as PIC receptors in retinal tissues of control rats and STZ rats. The levels of retinal HIF-1α were significantly increased in STZ rats 4-10 weeks after induction of hyperglycaemia as compared with control animals. With increasing HIF-1α retinal PICs including IL-1β, IL-6 and TNF-α, their respective receptors, namely IL-1R, IL-6R and TNFR1, were also elevated in STZ rats. Moreover, inhibition of HIF-1α by injection of 2-methoxyestradiol (2-MET) significantly decreased the amplified expression IL-6, TNF-α, IL-6R and TNFR1 in diabetic retina, but did not modify IL-1β pathway. In addition, we examined protein expression of Caspase-3 indicating cell apoptosis in the retina of STZ rats after infusing 2-MET, demonstrating that 2-MET attenuated an increase in Caspase-3 evoked by STZ. Hypoxia inducible factor subtype 1α (HIF-1α) activated in diabetic retina is likely to play a role in regulating pathophysiological process via IL-6 and TNF-α mechanism. This has pharmacological implications to target specific HIF-1α, IL-6 and TNF-α signalling pathway for dysfunction and vulnerability related to DR. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  1. Conditional IL-2 gene deletion: consequences for T cell proliferation

    Directory of Open Access Journals (Sweden)

    Kendall A Smith

    2012-05-01

    Full Text Available To explore the role of interleukin-2 (IL-2 in T cell proliferation, and to circumvent the IL-2 deficiency autoimmune syndrome of conventional il2 gene deletion, mice were created to allow conditional il2 gene deletion when treated with the estrogen analogue, tamoxifen (TAM as adults. Splenocytes from four different mouse strains, C57Bl/6 wild type (WT, conventional IL-2 (-/-, TAM-treated Cre recombinase negative (Cre-/IL2fl/fl, and Cre+/IL-2fl/fl (Cre+, were activated with anti-CD3 and anti-CD28, and monitored for CD4+ and CD8+ T cell lymphocyte blastogenesis, aerobic glycolysis, BrdU incorporation into newly synthesized DNA, and CFSE dye dilution to monitor cell division. IL-2 production was monitored by quantitative ELISA and multiple additional cytokines were monitored by protein-bead arrays. Splenocytes from conventional IL-2 (-/- and TAM-treated Cre+ mice resulted in undetectable IL-2 production, so that both strains were IL-2 deficient. As monitored by flow cytometry, activated CD4+ and CD8+ T cells from WT, Cre+ and Cre- mice all underwent blastogenesis, whereas far fewer cells from conventional IL-2 (-/- mice did so. By comparison, only cells from IL-2 sufficient WT and Cre- switched to aerobic glycolysis as evidenced by a drop in media pH. Blastogenesis was mirrored by BrdU incorporation and CFSE dye dilution by CD4+ and CD8+ T cells from WT, Cre+ and Cre- mice, which were all equivalent, while proliferation of cells from conventional IL-2 (-/- mice was compromised. Splenocytes from IL-2 deficient conventional IL-2 (-/- mice produced low or undetectable other γc-chain cytokines (IL-4, IL-7, IL-9, IL-13, IL-15, and IL-21, whereas production of these γc-chain cytokines from IL-2-deficient conditional IL-2 (-/- Cre+ mice were comparable with WT and Cre- mice. These results indicate that CD4+ and CD8+ T cell blastogenesis cannot be attributable to IL-2 alone, but a switch to aerobic glycolysis is attributable to IL-2, and proliferation

  2. Structural Characterisation Reveals Mechanism of IL-13-Neutralising Monoclonal Antibody Tralokinumab as Inhibition of Binding to IL-13Rα1 and IL-13Rα2.

    Science.gov (United States)

    Popovic, B; Breed, J; Rees, D G; Gardener, M J; Vinall, L M K; Kemp, B; Spooner, J; Keen, J; Minter, R; Uddin, F; Colice, G; Wilkinson, T; Vaughan, T; May, R D

    2017-01-20

    Interleukin (IL)-13 is a pleiotropic T helper type 2 cytokine frequently associated with asthma and atopic dermatitis. IL-13-mediated signalling is initiated by binding to IL-13Rα1, which then recruits IL-4Rα to form a heterodimeric receptor complex. IL-13 also binds to IL-13Rα2, considered as either a decoy or a key mediator of fibrosis. IL-13-neutralising antibodies act by preventing IL-13 binding to IL-13Rα1, IL-4Rα and/or IL-13Rα2. Tralokinumab (CAT-354) is an IL-13-neutralising human IgG4 monoclonal antibody that has shown clinical benefit in patients with asthma. To decipher how tralokinumab inhibits the effects of IL-13, we determined the structure of tralokinumab Fab in complex with human IL-13 to 2 Å resolution. The structure analysis reveals that tralokinumab prevents IL-13 from binding to both IL-13Rα1 and IL-13Rα2. This is supported by biochemical ligand-receptor interaction assay data. The tralokinumab epitope is mainly composed of residues in helices D and A of IL-13. It is mostly light chain complementarity-determining regions that are driving paratope interactions; the variable light complementarity-determining region 2 plays a key role by providing residue contacts for a network of hydrogen bonds and a salt bridge in the core of binding. The key residues within the paratope contributing to binding were identified as Asp50, Asp51, Ser30 and Lys31. This study demonstrates that tralokinumab prevents the IL-13 pharmacodynamic effect by binding to IL-13 helices A and D, thus preventing IL-13 from interacting with IL-13Rα1 and IL-13Rα2. Copyright © 2016 AstraZeneca. Published by Elsevier Ltd.. All rights reserved.

  3. Soluble CD30 serum level--an adequate marker for allograft rejection of solid organs?

    Science.gov (United States)

    Schlaf, G; Altermann, W W; Rothhoff, A; Seliger, B

    2007-11-01

    The CD30 molecule, a 120 kDa cell surface glycoprotein, is a member of the tumor necrosis factor receptor (TNF-R) superfamily and was originally identified on the surface of Reed-Sternberg cells and anaplastic large cell lymphomas in Hodgkin's disease patients. In addition to lymphoproliferative disorders the expression of CD30 was found in both activated CD8+ and CD4+ Th2 cells which lead to the activation of B-cells and consequently to the inhibition of the Th1-type cellular immunity. The membrane-bound CD30 molecule can be proteolytically cleaved, thereby generating a soluble form (sCD30) of about 85 kDa. Low serum levels of soluble CD30 were found in healthy humans, whereas increased sCD30 serum concentrations were detected under pathophysiological situations such as systemic lupus erythematosus, rheumatoid arthritis, certain viral infections and adult T cell leukaemia/lymphoma. In addition, it has recently been suggested that pre- or post-transplant levels of sCD30 represent a biomarker for graft rejection associated with an impaired outcome for transplanted patients. We here review (i) the current knowledge of the clinical significance of sCD30 serum levels for solid organ transplantations and (ii) our own novel data regarding inter- and intra-individual variations as well as time-dependent alterations of sCD30 levels in patients. (iii) Based on this information the implementation of sCD30 as predictive pre-transplant or post-transplant parameter for solid organ transplantation is critically discussed.

  4. Azilsartan increases levels of IL-10, down-regulates MMP-2, MMP-9, RANKL/RANK, Cathepsin K and up-regulates OPG in an experimental periodontitis model.

    Directory of Open Access Journals (Sweden)

    Aurigena Antunes de Araújo

    Full Text Available AIMS: The aim of this study was to evaluate the effects of azilsartan (AZT on bone loss, inflammation, and the expression of matrix metallo proteinases (MMPs, receptor activator of nuclear factor κB ligand (RANKL, receptor activator of nuclear factor κB (RANK, osteoprotegerin (OPG, cyclooxygenase-2 (COX-2, and cathepsin K in periodontal tissue in a rat model of ligature-induced periodontitis. MATERIALS AND METHODS: Male Wistar albino rats were randomly divided into 5 groups of 10 rats each: (1 nonligated, water; (2 ligated, water; (3 ligated, 1 mg/kg AZT; (4 ligated, 5 mg/kg AZT; and (5 ligated, 10 mg/kg AZT. All groups were treated with saline or AZT for 10 days. Periodontal tissues were analyzed by histopathology and immunohistochemical detection of MMP-2, MMP-9, COX-2, RANKL, RANK, OPG, and cathepsin K. Levels of IL-1β, IL-10, TNF-α, myeloperoxidase (MPO, and glutathione (GSH were determined by ELISA. RESULTS: Treatment with 5 mg/kg AZT resulted in reduced MPO (p<0.05 and IL-1β (p<0.05, increased levels of IL-10 (p<0.05, and reduced expression of MMP-2, MMP-9, COX-2, RANK, RANKL, cathepsin K, and increased expression of OPG. CONCLUSIONS: These findings reveal that AZT increases anti-inflammatory cytokines and GSH and decreases bone loss in ligature-induced periodontitis in rats.

  5. Effect of IL-6 on the insulin sensitivity in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Harder-Lauridsen, N M; Krogh-Madsen, R; Holst, Jens Juul

    2014-01-01

    increase the insulin-mediated glucose uptake. Men with type 2 diabetes not treated with insulin [n = 9, age 54.9 ± 9.7 (mean ± SD) yr, body mass index 34.8 ± 6.1 kg/m(2), HbA1c 7.0 ± 1.0%] received continuous intravenous infusion with either recombinant human IL-6 (rhIL-6) or placebo. After 1 h......Elevated interleukin-6 (IL-6) levels are associated with type 2 diabetes, but its role in glucose metabolism is controversial. We investigated the effect of IL-6 on insulin-stimulated glucose metabolism in type 2 diabetes patients and hypothesized that an acute, moderate IL-6 elevation would...

  6. Effects of the interleukin-6 (IL-6) polymorphism on toxic metal and trace element levels in placental tissues

    International Nuclear Information System (INIS)

    Kayaalti, Zeliha; Tekin, Deniz; Aliyev, Vugar; Yalcin, Serap; Kurtay, Guelay; Soeylemezoglu, Tuelin

    2011-01-01

    The placenta is a crucial organ of fetal origin that functions in providing nutrients to the fetus from the mother. During pregnancy, the need for essential micronutrients, such as Fe and Zn, increases due to the requirements of the growing fetus. Maternal Fe deficiency induces an increase in Cu levels and can also affect cytokine levels in the placenta. On the other hand, Cu deficiency, although not as common, can also have destructive effects on the fetus. Interleukin-6 (IL-6) is a pleiotropic cytokine with a wide range of biological activities, including such as immune responses, acute-phase reactions, and inflammation. The placenta produces a significant amount of IL-6 during pregnancy. The effects of the IL-6 -174 G/C single nucleotide polymorphism (SNP) on IL-6 gene transcription and on plasma cytokine levels were assessed in the present study. We investigated the association between the IL-6 -174 G/C polymorphism and trace element/toxic metal levels in placental tissues. For the purposes of this study, 95 healthy volunteers were evaluated. Presence of the IL-6 polymorphism was determined using the standard polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique, and metal levels were analyzed by atomic absorption spectrometry (AAS). Based on our data, there were no significant associations between the IL-6 -174 G/C polymorphism and Pb, Cd, Fe, or Zn levels in the placental tissues (p > 0.05), but a statistically significant association was detected between the polymorphism and Cu levels (p = 0.016). We determined that the mean Cu levels in the placental tissues from individuals with GG, GC and CC genotypes were 5.62 ± 1.98, 6.22 ± 3.22 and 8.00 ± 1.32 ppm, respectively, whereas the overall mean Cu level from the placental tissues was 5.98 ± 2.51 ppm. - Highlights: → We studied between the association of IL-6 polymorphism and metal levels in the placenta tissues. → It was the first report evaluating the association

  7. The Role of Serum Leptin and IL-6 Levels in Post Viral Hepatitis Cirrhotic patients

    International Nuclear Information System (INIS)

    Mohamed, S.K.

    2010-01-01

    Chronic liver disease is characterized by numerous metabolic alterations resulting in the clinical picture of malnutrition or even cachexia and contributing to complications such as hepatic encephalopathy and ascites. Leptin is a hormone that plays an important role in regulating energy intake and expenditure including appetite and metabolism. Interleukin-6 (IL-6), on the other hand, is generally considered to be one of the important cytokines that regulate immunologic and metabolic actions. The aim of the present study was to investigate serum leptin and IL-6 levels in liver cirrhosis, as well as to determine their levels in relation to liver functions and lipid profile. This study was conducted on 25 patients with post- viral hepatic cirrhosis compared to 20 healthy matched individuals served as controls with the same age and sex. The severity of the disease assessed with Child-Pugh criteria yielded 8 patients (3 women, 5 men) with stage A, 10 patients (4 women, 6 men) with stage B and 7 patients (2 women, 5 men) with stage C. Compared to controls, body mass index (BMI) was decreased and reached statistical significance in group C liver cirrhosis (P< 0.05). Also, serum leptin level was highly significantly decreased in the three groups, while IL-6 level showed highly significant increase. Leptin level negatively correlated with aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin and positively correlated with serum albumin, triglycerides (TG), cholesterol and low density lipoprotein (LDL). In contrast, serum IL-6 level positively correlated with parameters of liver functions and negatively correlated with parameters of lipid profile. Additionally, there was highly significant negative correlation between serum leptin and IL-6 levels (P < 0.001) in post-hepatic cirrhotic patients. We concluded that leptin and IL-6 have important role in diagnosis and prognosis of patients with post-hepatic liver cirrhosis

  8. The Role of Serum Leptin and IL-6 Levels in Post Viral Hepatitis Cirrhotic patients

    Energy Technology Data Exchange (ETDEWEB)

    Mohamed, S.K., E-mail: Safaa-K-mohamed@hotmail.co [Health Radiation Research Department, National Center for Radiation Research and Technology, P. O. Box:29 Nasr City, Cairo (Egypt)

    2010-07-01

    Chronic liver disease is characterized by numerous metabolic alterations resulting in the clinical picture of malnutrition or even cachexia and contributing to complications such as hepatic encephalopathy and ascites. Leptin is a hormone that plays an important role in regulating energy intake and expenditure including appetite and metabolism. Interleukin-6 (IL-6), on the other hand, is generally considered to be one of the important cytokines that regulate immunologic and metabolic actions. The aim of the present study was to investigate serum leptin and IL-6 levels in liver cirrhosis, as well as to determine their levels in relation to liver functions and lipid profile. This study was conducted on 25 patients with post- viral hepatic cirrhosis compared to 20 healthy matched individuals served as controls with the same age and sex. The severity of the disease assessed with Child-Pugh criteria yielded 8 patients (3 women, 5 men) with stage A, 10 patients (4 women, 6 men) with stage B and 7 patients (2 women, 5 men) with stage C. Compared to controls, body mass index (BMI) was decreased and reached statistical significance in group C liver cirrhosis (P< 0.05). Also, serum leptin level was highly significantly decreased in the three groups, while IL-6 level showed highly significant increase. Leptin level negatively correlated with aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin and positively correlated with serum albumin, triglycerides (TG), cholesterol and low density lipoprotein (LDL). In contrast, serum IL-6 level positively correlated with parameters of liver functions and negatively correlated with parameters of lipid profile. Additionally, there was highly significant negative correlation between serum leptin and IL-6 levels (P < 0.001) in post-hepatic cirrhotic patients. We concluded that leptin and IL-6 have important role in diagnosis and prognosis of patients with post-hepatic liver cirrhosis

  9. Multiple Myeloma-Derived Exosomes Regulate the Functions of Mesenchymal Stem Cells Partially via Modulating miR-21 and miR-146a

    Directory of Open Access Journals (Sweden)

    Qian Cheng

    2017-01-01

    Full Text Available Exosomes derived from cancer cells can affect various functions of mesenchymal stem cells (MSCs via conveying microRNAs (miRs. miR-21 and miR-146a have been demonstrated to regulate MSC proliferation and transformation. Interleukin-6 (IL-6 secreted from transformed MSCs in turn favors the survival of multiple myeloma (MM cells. However, the effects of MM exosomes on MSC functions remain largely unclear. In this study, we investigated the effects of OPM2 (a MM cell line exosomes (OPM2-exo on regulating the proliferation, cancer-associated fibroblast (CAF transformation, and IL-6 secretion of MSCs and determined the role of miR-21 and miR-146a in these effects. We found that OPM2-exo harbored high levels of miR-21 and miR-146a and that OPM2-exo coculture significantly increased MSC proliferation with upregulation of miR-21 and miR-146a. Moreover, OPM2-exo induced CAF transformation of MSCs, which was evidenced by increased fibroblast-activated protein (FAP, α-smooth muscle actin (α-SMA, and stromal-derived factor 1 (SDF-1 expressions and IL-6 secretion. Inhibition of miR-21 or miR-146a reduced these effects of OPM2-exo on MSCs. In conclusion, MM could promote the proliferation, CAF transformation, and IL-6 secretion of MSCs partially through regulating miR21 and miR146a.

  10. CCL2/CCL5 secreted by the stroma induce IL-6/PYK2 dependent chemoresistance in ovarian cancer.

    Science.gov (United States)

    Pasquier, Jennifer; Gosset, Marie; Geyl, Caroline; Hoarau-Véchot, Jessica; Chevrot, Audrey; Pocard, Marc; Mirshahi, Massoud; Lis, Raphael; Rafii, Arash; Touboul, Cyril

    2018-02-19

    Minimal residual disease is the main issue of advanced ovarian cancer treatment. According to the literature and previous results, we hypothesized that Mesenchymal Stromal Cells (MSC) could support this minimal residual disease by protecting ovarian cancer cells (OCC) from chemotherapy. In vitro study confirmed that MSC could induce OCC chemoresistance without contact using transwell setting. Further experiments showed that this induced chemoresistance was dependent on IL-6 OCC stimulation. We combined meticulous in vitro profiling and tumor xenograft models to study the role of IL-6 in MSC/OCC intereactions. We demonstrated that Tocilizumab® (anti-IL-6R therapy) in association with chemotherapy significantly reduced the peritoneal carcinosis index (PCI) than chemotherapy alone in mice xenografted with OCCs+MSCs. Further experiments showed that CCL2 and CCL5 are released by MSC in transwell co-culture and induce OCCs IL-6 secretion and chemoresistance. Finally, we found that IL-6 induced chemoresistance was dependent on PYK2 phosphorylation. These findings highlight the potential key role of the stroma in protecting minimal residual disease from chemotherapy, thus favoring recurrences. Future clinical trials targeting stroma could use anti-IL-6 therapy in association with chemotherapy.

  11. Serum 25-OH vitamin D level in treatment-naïve systemic lupus erythematosus patients: Relation to disease activity, IL-23 and IL-17.

    Science.gov (United States)

    Shahin, D; El-Farahaty, R M; Houssen, M E; Machaly, S A; Sallam, M; ElSaid, T O; Neseem, N O

    2017-08-01

    Objectives The aim of this study was to assess the vitamin D status in treatment-naïve SLE patients and its association with clinical and laboratory markers of disease activity, including serum levels of IL-17 and IL-23. Methods Fifty-seven treatment-naïve SLE patients along with 42 matched controls were included. SLEDAI score was used to estimate disease activity. Serum levels of 25(OH) D, IL-17 and IL-23 were measured. Results The median level of 25(OH) D in SLE patients (40.8; 4-70 ng/ml) was significantly lower than in the controls (47; 25-93 ng/ml) ( P = 0.001). A total of 38.6% of SLE cases had 25 (OH) D levels < 30 ng/ml (hypovitaminosis D) vs. 4.8% of the controls ( P < 0.0001). Apart from thrombocytopenia, vitamin D was not associated with clinical signs of SLE. There were negative correlations between serum 25(OH) D and serum levels of IL-17, IL-23 and ANA (rho = -0.5, -0.8, -0.5, P ≤ 0.05) in SLE patients. Conclusion Hypovitaminosis D is prevalent in treatment naïve SLE patients. It contributes to ANA antibody production and is associated with high serum levels of IL-23 and IL-17; thus they may trigger the inflammatory process in SLE.

  12. Water-soluble, triflate-based, pyrrolidinium ionic liquids

    International Nuclear Information System (INIS)

    Moreno, M.; Montanino, M.; Carewska, M.; Appetecchi, G.B.; Jeremias, S.; Passerini, S.

    2013-01-01

    Highlights: • Water-soluble, pyrrolidinium triflate ILs as solvents for extraction processes. • Electrolyte components for high safety, electrochemical devices. • Effect of the oxygen atom in the alkyl main side chain of pyrrolidinium cation. -- Abstract: The physicochemical and electrochemical properties of the water-soluble, N-methoxyethyl-N-methylpyrrolidinium trifluoromethanesulfonate (PYR 1(2O1) OSO 2 CF 3 ) ionic liquid (IL) were investigated and compared with those of commercial N-butyl-N-methylpyrrolidinium trifluoromethanesulfonate (PYR 14 OSO 2 CF 3 ). The results have shown that the transport properties are well correlated with the rheological and thermal behavior. The incorporation of an oxygen atom in the pyrrolidinium cation aliphatic side chain resulted in enhanced flexibility of the ether side chain, this supporting for the higher ionic conductivity, self-diffusion coefficient and density of PYR 1(2O1) OSO 2 CF 3 with respect to PYR 14 OSO 2 CF 3 , whereas no relevant effect on the crystallization of the ionic liquid was found. Finally, the presence of the ether side chain material in the pyrrolidinium cation led to a reduction in electrochemical stability, particularly on the cathodic verse

  13. Effect of Helicobacter pylori infection on IL-8, IL-1beta and COX-2 expression in patients with chronic gastritis and gastric cancer.

    Science.gov (United States)

    Bartchewsky, Waldemar; Martini, Mariana Rocha; Masiero, Mariana; Squassoni, Aline Candido; Alvarez, Marisa Claudia; Ladeira, Marcelo Sady; Salvatore, Daisy; Trevisan, Miriam; Pedrazzoli, José; Ribeiro, Marcelo Lima

    2009-01-01

    Helicobacter pylori infection is related to gastric cancer development, and chronic inflammation is presumed to be the main cause. The aim of the present study was to evaluate the influence of H. pylori cagA, vacA, iceA, and babA genotypes on COX-2, IL-1beta, and IL-8 expression. Of the 217 patients included in the study, 26 were uninfected, 127 had chronic gastritis and were H. pylori-positive, and 64 had gastric cancer. Bacterial genotypes were evaluated by polymerase chain reaction (PCR), and the expression values were determined by quantitative real-time PCR and immunohistochemistry. An association was found between the infection with cagA, vacA s1m1 strains and gastric cancer development. Regarding the 3' region of the cagA gene, we also found an association between the infection with cagA EPIYA-ABCCC strains and clinical outcome. Higher levels of IL-8, IL-1beta, and COX-2 were detected in gastric mucosa from infected patients with chronic gastritis, and they were also associated with the infection by cagA, vacA s1m1 strains. The IL-8 and IL-1beta levels decrease significantly from chronic gastritis to gastric cancer, while the relative expression remained unaltered when COX-2 expression was analyzed among patients with gastritis and cancer. Since inflammatory response to H. pylori infection plays an important role in cellular proliferation and gastric mucosal damage, the up-regulation of IL-1beta, IL-8, and COX-2 in patients with chronic gastritis has an important clinical implication in gastric carcinogenesis.

  14. Role of periostin, FENO, IL-13, lebrikzumab, other IL-13 antagonist and dual IL-4/IL-13 antagonist in asthma.

    Science.gov (United States)

    Agrawal, Swati; Townley, Robert G

    2014-02-01

    Asthma markedly diminishes quality of life due to limited activity, absences from work or school and hospitalizations. Patients with severe asthma which are not controlled despite taking effective therapy are most in need of new treatment approaches. IL-13 was demonstrated as 'central mediator of allergic asthma'. IL-13 has been implicated in the pathogenesis of asthma, idiopathic pulmonary fibrosis and COPD. IL-13 levels in the sputum and bronchial biopsy samples remain elevated in severe asthma despite the use of inhaled and systemic corticosteroids. Thus, IL-13 is a mediator involved in corticosteroid resistance. Periostin enhances profibrotic TGF-β signaling in subepithelial fibrosis associated with asthma. IL-13 induces bronchial epithelial cells to secrete periostin. Periostin may be a biomarker for Th2 induced airway inflammation. Lebrikizumab is a monoclonal antibody against IL-13. Lebrikizumab improved lung function in asthmatics who were symptomatic despite treatment with long acting beta agonist and inhaled corticosteroids and provided benefit in the treatment of severe uncontrolled asthma. Lebrikizumab block IL-13 signaling through the IL-13Rα1/IL-4Rα receptor. There was a larger reduction in FENO in the high periostin subgroup than in the low periostin subgroup (34.4 vs 4.3%). Serum CCL17, CCL13 and total IgE levels decreased in the lebrikizumab group.

  15. Lack of association between rheumatoid arthritis and genetic variants rs10889677, rs11209026 and rs2201841 of IL-23R gene.

    Science.gov (United States)

    Paradowska-Gorycka, Agnieszka; Malinowski, Damian; Haladyj, Ewa; Olesinska, Marzena; Safranow, Krzysztof; Pawlik, Andrzej

    2018-01-19

    Rheumatoid arthritis (RA) is an autoimmune diseases, where different genetic variants in cytokine genes may play a pathogenic role. A GWAS in autoimmune diseases highlighted the IL-23R gene as a one of the susceptibility factors. We examined three candidate single nucleotide polymorphisms (SNPs) rs10889677, rs11209026 and rs2201841 of the IL-23R gene, as well as determined their possible association with RA in a Polish population. The IL-23R gene polymorphisms were genotyped for 422 RA patients and 348 healthy individuals using TaqMan SNP genotyping assay. The genotypes frequency did not deviate from HWE in each examined group. A comparison of the allele as well as genotype frequencies of the IL-23R polymorphisms under codominant, dominant and recessive genetic model revealed no significant differences between RA patients and healthy subjects. We also demonstrated that IL-23R rs2201841 and rs11209026 as well as rs11209026 and rs10889677 were in complete linkage disequilibrium (D'=1.0). Our genotype-phenotype analysis demonstrated that in carriers of rs10889677C and/or rs2201841A allele the RF, extra-articular manifestations and erosion were more frequent present than in patients with rs10889677A and/or rs2201841A allele, although this association was not significant. Present findings indicated that the autoimmune disease-associated genetic variants in IL-23R gene are not associated with RA in the Polish population. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  16. T helper 2 (Th2) cell differentiation, type 2 innate lymphoid cell (ILC2) development and regulation of interleukin-4 (IL-4) and IL-13 production.

    Science.gov (United States)

    Zhu, Jinfang

    2015-09-01

    Interleukin-4 (IL-4), IL-5 and IL-13, the signature cytokines that are produced during type 2 immune responses, are critical for protective immunity against infections of extracellular parasites and are responsible for asthma and many other allergic inflammatory diseases. Although many immune cell types within the myeloid lineage compartment including basophils, eosinophils and mast cells are capable of producing at least one of these cytokines, the production of these "type 2 immune response-related" cytokines by lymphoid lineages, CD4 T helper 2 (Th2) cells and type 2 innate lymphoid cells (ILC2s) in particular, are the central events during type 2 immune responses. In this review, I will focus on the signaling pathways and key molecules that determine the differentiation of naïve CD4 T cells into Th2 cells, and how the expression of Th2 cytokines, especially IL-4 and IL-13, is regulated in Th2 cells. The similarities and differences in the differentiation of Th2 cells, IL-4-producing T follicular helper (Tfh) cells and ILC2s as well as their relationships will also be discussed. Published by Elsevier Ltd.

  17. T helper 2 (Th2) cell differentiation, type 2 innate lymphoid cell (ILC2) development and regulation of interleukin-4 (IL-4) and IL-13 production

    Science.gov (United States)

    Zhu, Jinfang

    2015-01-01

    Interleukin-4 (IL-4), IL-5 and IL-13, the signature cytokines that are produced during type 2 immune responses, are critical for protective immunity against infections of extracellular parasites and are responsible for asthma and many other allergic inflammatory diseases. Although many immune cell types within the myeloid lineage compartment including basophils, eosinophils and mast cells are capable of producing at least one of these cytokines, the production of these “type 2 immune response-related” cytokines by lymphoid lineages, CD4 T helper 2 (Th2) cells and type 2 innate lymphoid cells (ILC2s) in particular, are the central events during type 2 immune responses. In this review, I will focus on the signaling pathways and key molecules that determine the differentiation of naïve CD4 T cells into Th2 cells, and how the expression of Th2 cytokines, especially IL-4 and IL-13, is regulated in Th2 cells. The similarities and differences in the differentiation of Th2 cells, IL-4-producing T follicular helper (Tfh) cells and ILC2s as well as their relationships will also be discussed. PMID:26044597

  18. Association of the IL4R single-nucleotide polymorphism I50V with recurrent spontaneous abortion (RSA).

    Science.gov (United States)

    Tavasolian, Fataneh; Abdollahi, Elham; Samadi, Morteza

    2014-07-01

    Recurrent spontaneous abortion (RSA) is defined as three or more consecutive abortions before the 20th week of gestation. There is increasing evidence to support an immunological mechanism for the occurrence of RSA. The purpose of our study was to examine whether single-nucleotide polymorphisms (SNPs) of the interleukin-4 receptor gene IL4R influence susceptibility to, recurrent spontaneous abortion. This is a case-control study. We recruited 200 patients with RSA (case group) using established diagnostic criteria and 200, normal individuals (control group) at the fertility and infertility center in Yazd city and Isfahan city during 2012 to 2013. We screened the I50V variant in IL-4R in patients and controls by PCR-RFLF method, and we performed an association analysis between I50V variant and RSA.the data was analyzed by spss 16 software using Chi-square test. No differences in the genotype and allele frequencies of the I50V SNPs were identified between patients with RSA and healthy controls. The frequency of SNP in IL-4 receptor (I50V) in patients with recurrent spontaneous abortion did not differ significantly compared with the control group. Analysis of IL4R SNP haplotypes or complex alleles suggested no dominant protection in patients with RSA.

  19. Cannabinoid inhibition of adenylate cyclase-mediated signal transduction and interleukin 2 (IL-2) expression in the murine T-cell line, EL4.IL-2.

    Science.gov (United States)

    Condie, R; Herring, A; Koh, W S; Lee, M; Kaminski, N E

    1996-05-31

    Cannabinoid receptors negatively regulate adenylate cyclase through a pertussis toxin-sensitive GTP-binding protein. In the present studies, signaling via the adenylate cyclase/cAMP pathway was investigated in the murine thymoma-derived T-cell line, EL4.IL-2. Northern analysis of EL4.IL-2 cells identified the presence of 4-kilobase CB2 but not CB1 receptor-subtype mRNA transcripts. Southern analysis of genomic DNA digests for the CB2 receptor demonstrated identical banding patterns for EL4.IL-2 cells and mouse-derived DNA, both of which were dissimilar to DNA isolated from rat. Treatment of EL4.IL-2 cells with either cannabinol or Delta9-THC disrupted the adenylate cyclase signaling cascade by inhibiting forskolin-stimulated cAMP accumulation which consequently led to a decrease in protein kinase A activity and the binding of transcription factors to a CRE consensus sequence. Likewise, an inhibition of phorbol 12-myristate 13-acetate (PMA)/ionomycin-induced interleukin 2 (IL-2) protein secretion, which correlated to decreased IL-2 gene transcription, was induced by both cannabinol and Delta9-THC. Further, cannabinoid treatment also decreased PMA/ionomycin-induced nuclear factor binding to the AP-1 proximal site of the IL-2 promoter. Conversely, forskolin enhanced PMA/ionomycin-induced AP-1 binding. These findings suggest that inhibition of signal transduction via the adenylate cyclase/cAMP pathway induces T-cell dysfunction which leads to a diminution in IL-2 gene transcription.

  20. Targeted sequencing identifies associations between IL7R-JAK mutations and epigenetic modulators in T-cell acute lymphoblastic leukemia

    Science.gov (United States)

    Vicente, Carmen; Schwab, Claire; Broux, Michaël; Geerdens, Ellen; Degryse, Sandrine; Demeyer, Sofie; Lahortiga, Idoya; Elliott, Alannah; Chilton, Lucy; La Starza, Roberta; Mecucci, Cristina; Vandenberghe, Peter; Goulden, Nicholas; Vora, Ajay; Moorman, Anthony V.; Soulier, Jean; Harrison, Christine J.; Clappier, Emmanuelle; Cools, Jan

    2015-01-01

    T-cell acute lymphoblastic leukemia is caused by the accumulation of multiple oncogenic lesions, including chromosomal rearrangements and mutations. To determine the frequency and co-occurrence of mutations in T-cell acute lymphoblastic leukemia, we performed targeted re-sequencing of 115 genes across 155 diagnostic samples (44 adult and 111 childhood cases). NOTCH1 and CDKN2A/B were mutated/deleted in more than half of the cases, while an additional 37 genes were mutated/deleted in 4% to 20% of cases. We found that IL7R-JAK pathway genes were mutated in 27.7% of cases, with JAK3 mutations being the most frequent event in this group. Copy number variations were also detected, including deletions of CREBBP or CTCF and duplication of MYB. FLT3 mutations were rare, but a novel extracellular mutation in FLT3 was detected and confirmed to be transforming. Furthermore, we identified complex patterns of pairwise associations, including a significant association between mutations in IL7R-JAK genes and epigenetic regulators (WT1, PRC2, PHF6). Our analyses showed that IL7R-JAK genetic lesions did not confer adverse prognosis in T-cell acute lymphoblastic leukemia cases enrolled in the UK ALL2003 trial. Overall, these results identify interconnections between the T-cell acute lymphoblastic leukemia genome and disease biology, and suggest a potential clinical application for JAK inhibitors in a significant proportion of patients with T-cell acute lymphoblastic leukemia. PMID:26206799

  1. Urinary water-soluble vitamins and their metabolite contents as nutritional markers for evaluating vitamin intakes in young Japanese women.

    Science.gov (United States)

    Fukuwatari, Tsutomu; Shibata, Katsumi

    2008-06-01

    Little information is available to estimate water-soluble vitamin intakes from urinary vitamins and their metabolite contents as possible nutritional markers. Determination of the relationships between the oral dose and urinary excretion of water-soluble vitamins in human subjects contributes to finding valid nutrition markers of water-soluble vitamin intakes. Six female Japanese college students were given a standard Japanese diet in the first week, the same diet with a synthesized water-soluble vitamin mixture as a diet with approximately onefold vitamin mixture based on Dietary Reference Intakes (DRIs) for Japanese in the second week, with a threefold vitamin mixture in the third week, and a sixfold mixture in the fourth week. Water-soluble vitamins and their metabolites were measured in the 24-h urine collected each week. All urinary vitamins and their metabolite levels except vitamin B(12) increased linearly in a dose-dependent manner, and highly correlated with vitamin intake (r=0.959 for vitamin B(1), r=0.927 for vitamin B(2), r=0.965 for vitamin B(6), r=0.957 for niacin, r=0.934 for pantothenic acid, r=0.907 for folic acid, r=0.962 for biotin, and r=0.952 for vitamin C). These results suggest that measuring urinary water-soluble vitamins and their metabolite levels can be used as good nutritional markers for assessing vitamin intakes.

  2. IL-33 is related to innate immune activation and sensitization to HDM in mild steroid-free asthma

    DEFF Research Database (Denmark)

    Porsbjerg, Celeste; Baines, Katie; Gibson, Peter

    2015-01-01

    = 0.04; TLR4: 0.68, P HDMs). CONCLUSION: In mild untreated asthma, the expression of IL-33 mRNA in bronchial mucosa is related to innate immune activation and allergic sensitization to HDM, rather than epithelial damage, and correlates with Fe.......04). There was a positive correlation between IL-33 mRNA expression and the level of FeNO (r = 0.56, P = 0.01), whereas there was no association with airway or blood eosinophils. IL-33 expression was unrelated to loss of epithelial integrity, but correlated with an increased expression of TLR2 and TLR4 (TLR2: r = 0.47, P...

  3. Clinical significance of determination of changes of serum HA, IL-2 and TNF-α contents in patients with psoriasis

    International Nuclear Information System (INIS)

    Ren Hong

    2006-01-01

    Objective: To investigate the changes of serum HA, IL-2 and TNF-α contents in patients with psoriasis. Methods: Serum HA, TNF-α levels were measured with RIA and IL-2 levels was measured with ELISA in 47 patients with psoriasis as well as 35 controls. Results: The serum HA, TNF-α levels were significantly higher in the patients than those in controls (P < 0. 01), while the serum IL-2 levels were significantly lower (P<0.01). Conclusion: Determination of serum HA, IL-2 and TNF-α contents would be clinically useful for understanding the disturbances of immunomodulation in these patients. (authors)

  4. Cytokine profile and nitric oxide levels in sera from patients with brucellosis

    Directory of Open Access Journals (Sweden)

    Refik M.

    2004-01-01

    Full Text Available The aims of this study were to investigate the serum levels of some cytokines [tumor necrosis factor-alpha (TNF-alpha, interleukin 1ß (IL-1ß, IL-2R, IL-6, and IL-8] and nitric oxide (NO levels in patients with untreated brucellosis and to test the correlation of these parameters with each other. The study was conducted on 67 subjects, 37 patients with brucellosis and 30 healthy individuals with no history of Brucella infection. Brucellosis was identified by a positive blood culture and/or increased Brucella antibodies in serological tests in addition to compatible clinical symptoms. Cytokine profile analysis was performed by the immulite chemiluminescent enzyme immunometric assay whose inter- and intra-assay coefficients of variance were 2.6-3.6 and 4.4-8.5%, respectively. The levels of nitrites/nitrates, which are representative of NO levels, were measured by the Griess method. Patients with brucellosis had significantly elevated serum levels of nitrites/nitrates, IL-2R, IL-6 and IL-8 (mean ± SD, 102.8 ± 23.8 µmol/l, 806.1 ± 58.5 U/ml, 21.1 ± 2.3 pg/ml, and 8.8 ± 1.6 pg/ml, respectively compared to healthy controls, whereas TNF-alpha and IL-1ß levels were unchanged. No statistically significant correlation was detected between any of the studied cytokine levels and nitrate/nitrite concentrations according to Pearson's linear correlation test. We conclude that only IL-6, IL-8 and IL-2R are elevated in brucellosis and the extent of elevation depends on the severity and clinical pattern of the disease. Moderate elevation in serum NO was comparable to that observed in previous studies. This explains the absence or very rare occurrence of septic shock in brucellosis.

  5. Circulating levels of TNF-alpha and IL-6-relation to truncal fat mass and muscle mass in healthy elderly individuals and in patients with type-2 diabetes

    DEFF Research Database (Denmark)

    Pedersen, Maria; Bruunsgaard, Helle; Weis, Nina

    2003-01-01

    The purpose of the current study was to test the hypothesis that an altered fat distribution in elderly healthy subjects and in patients with type-2 diabetes contributes to high circulating levels of interleukin (IL)-6 and tumor necrotic factor (TNF)-alpha, which secondly is related to lower muscle...... mass. Twenty young controls, (20-35 yr), 20 healthy elderly subjects (65-80 yr) and 16 elderly patients with type 2 diabetes (65-80 yr) were included in a cross sectional study. Plasma levels of TNF-alpha and IL-6 were measured after an overnight fast. Dual-energy X-ray absorptiometry and total body...... to lower ASM and BCM in elderly men both in a univariate regression analysis and a multivariate regression analysis. In conclusion, high plasma levels of TNF-alpha and IL-6 in elderly healthy people and in patients with type 2 diabetes are associated with increased truncal fat mass, suggesting...

  6. IL-8 Expression in Granulocytic Epithelial Lesions of Idiopathic Duct-centric Pancreatitis (Type 2 Autoimmune Pancreatitis).

    Science.gov (United States)

    Ku, Yuna; Hong, Seung-Mo; Fujikura, Kohei; Kim, Sung Joo; Akita, Masayuki; Abe-Suzuki, Shiho; Shiomi, Hideyuki; Masuda, Atsuhiro; Itoh, Tomoo; Azuma, Takeshi; Kim, Myung-Hwan; Zen, Yoh

    2017-08-01

    Type 2 autoimmune pancreatitis (type 2 AIP) develops in isolation or sometimes in association with ulcerative colitis. Its diagnosis requires the histologic confirmation of granulocytic epithelial lesions (GELs) with no diagnostic biomarker currently available. This study aimed to elucidate the tissue expression of cytokines and their diagnostic value in this condition. In quantitative polymerase chain reaction for multiple cytokines using tissue-derived mRNA, the expression level of interleukin (IL)-8 was markedly higher in type 2 AIP than in type 1 AIP (Ppancreatitis adjacent to pancreatic cancers (peritumoral pancreatitis) exhibited IL-8 expression in the epithelium (3/12; 25%) and inflammatory cells (10/12; 83%), expression levels were significantly lower than those in type 2 AIP (Ppancreatitis with 92% sensitivity and 92% to 100% specificity. Furthermore, CD3/IL-8-coexpressing lymphocytes were almost restricted to type 2 AIP. Interestingly, a similar pattern of IL-8 expression was also observed in colonic biopsies of ulcerative colitis. In conclusion, the overexpression of IL-8 may underlie the development of GELs in type 2 AIP, and IL-8 immunostaining or IL-8/CD3 double staining may become an ancillary method for its diagnosis. The similar expression pattern of IL-8 in ulcerative colitis also suggests a pathogenetic link between the 2 conditions.

  7. Blockade of the IL-6 trans-signalling/STAT3 axis suppresses cachexia in Kras-induced lung adenocarcinoma.

    Science.gov (United States)

    Miller, A; McLeod, L; Alhayyani, S; Szczepny, A; Watkins, D N; Chen, W; Enriori, P; Ferlin, W; Ruwanpura, S; Jenkins, B J

    2017-05-25

    Lung cancer is the leading cause of cancer death worldwide, and is frequently associated with the devastating paraneoplastic syndrome of cachexia. The potent immunomodulatory cytokine interleukin (IL)-6 has been linked with the development of lung cancer as well as cachexia; however, the mechanisms by which IL-6 promotes muscle wasting in lung cancer cachexia are ill-defined. In this study, we report that the gp130 F/F knock-in mouse model displaying hyperactivation of the latent transcription factor STAT3 via the common IL-6 cytokine family signalling receptor, gp130, develops cachexia during Kras-driven lung carcinogenesis. Specifically, exacerbated weight loss, early mortality and reduced muscle and adipose tissue mass were features of the gp130 F/F :Kras G12D model, but not parental Kras G12D mice in which STAT3 was not hyperactivated. Gene expression profiling of muscle tissue in cachectic gp130 F/F :Kras G12D mice revealed the upregulation of IL-6 and STAT3-target genes compared with Kras G12D muscle tissue. These cachectic features of gp130 F/F :Kras G12D mice were abrogated upon the genetic normalization of STAT3 activation or ablation of IL-6 in gp130 F/F :Kras G12D :Stat3 -/+ or gp130 F/F :Kras G12D :Il6 -/- mice, respectively. Furthermore, protein levels of the soluble IL-6 receptor (sIL-6R), which is the central facilitator of IL-6 trans-signalling, were elevated in cachectic muscle from gp130 F/F :Kras G12D mice, and the specific blockade of IL-6 trans-signalling, but not classical signalling, with an anti-IL-6R antibody ameliorated cachexia-related characteristics in gp130 F/F :Kras G12D mice. Collectively, these preclinical findings identify trans-signalling via STAT3 as the signalling modality by which IL-6 promotes muscle wasting in lung cancer cachexia, and therefore support the clinical evaluation of the IL-6 trans-signalling/STAT3 axis as a therapeutic target in advanced lung cancer patients presenting with cachexia.

  8. IL-1 receptor antagonism and muscle gene expression in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Berchtold, L. A.; Larsen, C. M.; Vaag, A.

    2009-01-01

    ). To investigate the effects of IL-1Ra in insulin-sensitive tissue, gene expression levels in skeletal muscle from type 2 diabetic patients treated with IL-1Ra were analysed. Methods. Gene expression profiles in vastus lateralis muscle biopsies from five obese patients (BMI>27) were determined before and after 13......RT-PCR, were significantly altered when comparing the number of transcripts before and after treatment for each individual. Conclusion. Treatment with IL-1Ra did not significantly affect gene expression levels in skeletal muscle in this limited and selected sample of obese patients with type 2 diabetes. Larger...

  9. Effect of IL-2 on recovery of proliferation ability of irradiated T lymphocytes

    International Nuclear Information System (INIS)

    Wang Ninghai; Zhang Lansheng

    1989-01-01

    3 H-thymidine incorporation assay was used to evaluated the proliferation ability of normal human peripheral blood T lymphocytes irradiated with or without exogenous IL-2 by 60 Co γ-ray at various doses after exposure to 1, 2.5, 5, 10, 20 and 40 Gy γ-ray, the DNA synthesis is blocked. It indicated IL-2 has damage effect on the proliferation ability of T cells. 3 H-thymidine incorporation rate in cells decreases with increasing dose of irradiation. Incorporation of 3 H-Tdk in irradiated groups in the dose range of 1 to 40 Gy was compared with that in the control group. The incorporation rate 3 H-TdR in these irradiated groups is 27 to 82 % of that in control group. The inhibition of lymphocyte proliferation was partially enhanced by adding IL-2, but the inhibiting effect on proliferation of human peripheral blood lymphocytes exposed to irradiation at more than 10 Gy is not reversible

  10. Macrophages as IL-25/IL-33-responsive cells play an important role in the induction of type 2 immunity.

    Directory of Open Access Journals (Sweden)

    Zhonghan Yang

    Full Text Available Type 2 immunity is essential for host protection against nematode infection but is detrimental in allergic inflammation or asthma. There is a major research focus on the effector molecules and specific cell types involved in the initiation of type 2 immunity. Recent work has implicated an important role of epithelial-derived cytokines, IL-25 and IL-33, acting on innate immune cells that are believed to be the initial sources of type 2 cytokines IL-4/IL-5/IL-13. The identities of the cell types that mediate the effects of IL-25/IL-33, however, remain to be fully elucidated. In the present study, we demonstrate that macrophages as IL-25/IL-33-responsive cells play an important role in inducing type 2 immunity using both in vitro and in vivo approaches. Macrophages produced type 2 cytokines IL-5 and IL-13 in response to the stimulation of IL-25/IL-33 in vitro, or were the IL-13-producing cells in mice administrated with exogenous IL-33 or infected with Heligmosomoides bakeri. In addition, IL-33 induced alternative activation of macrophages primarily through autocrine IL-13 activating the IL-4Rα-STAT6 pathway. Moreover, depletion of macrophages attenuated the IL-25/IL-33-induced type 2 immunity in mice, while adoptive transfer of IL-33-activated macrophages into mice with a chronic Heligmosomoides bakeri infection induced worm expulsion accompanied by a potent type 2 protective immune response. Thus, macrophages represent a unique population of the innate immune cells pivotal to type 2 immunity and a potential therapeutic target in controlling type 2 immunity-mediated inflammatory pathologies.

  11. Neurocognitive function, brain-derived neurotrophic factor (BDNF) and IL-6 levels in cancer patients with depression.

    Science.gov (United States)

    Jehn, C F; Becker, B; Flath, B; Nogai, H; Vuong, L; Schmid, P; Lüftner, D

    2015-10-15

    Increased IL-6 and decreased brain-derived neurotrophic factor (BDNF) levels have been implicated in the pathophysiology of depression. The objective was to assess the influence of BDNF and IL-6 on cognitive function and depression in patients with cancer. Serum BDNF and plasma IL-6 were measured in patients with metastatic cancer. Diagnosis of depression was established according to DSM-IV criteria. Cognitive function was assessed by the Verbal Learning and Memory Test (VLMT). A total of 59 patients were recruited in this study. Only IL-6 levels were significantly elevated in patients with clinical depression (35.7 vs. 6.9 pg/ml; pBDNF levels (p=0.16). Patients with clinical depression showed significant impairment of short-term memory (STM) (24.4 vs. 37.5; p=0.01), but not of long-term memory (LTM) (3.9 vs. 2.8; p=0.3). STM was dependent on the level of BDNF and younger age (b=0.60; p=0.001; b= -0.63; p=0.003, respectively). IL-6 was not only strongly associated with depression, but was an independent predictor of BDNF level as well (b= -0.50; p=0.01). LTM was associated only with a good KPS (b=0.47; p=0.037). Hemoglobin levels and the prior number of chemotherapy lines were not predictive of memory performance. Low BDNF is associated with cognitive impairment, STM, in patients with cancer, however no influence on depression could be found. IL-6 is strongly associated with depression and an independent predictor of BDNF levels. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. The Suppression of Adjuvant-induced Inflammation and the Inhibition of the Serum and Tissue IL-17, TNF-α and IL-1β levels by Thymol and Carvacrol

    Directory of Open Access Journals (Sweden)

    Nasser Gholijani

    2017-06-01

    Full Text Available Background and Aim: Thymol and carvacrol are two important components of thyme that have multiple medicinal uses. This study investigates the in vivo effects of these natural products on adjuvant-induced inflammation and secretion of interleukin (IL-17 and key inflammatory cytokines in rats. Materials and Methods: We injected complete Freund’s adjuvant (CFA into the hind paws of rats in order to induce inflammation. Each of the CFA-treated rat groups received gavages of thymol, carvacrol, or vehicle (CFA-only group. Rats’ paws and ankle edema were measured and then we were able to determine an inflammatory score based on the results. After 72 h of inflammation induction, sera were collected and subsequently inflamed tissue extracts were prepared for cytokine assay by ELISA. Results: Both components significantly decreased paw edema in rats (p<0.01. Thymol decreased ankle edema to 61.6% of edema in CFA-only rats (p<0.001. We observed a decreased inflammatory score in the thymol and carvacrol-treated rats. The evaluation of the tissue and serum inflammatory cytokine levels showed that both components decreased tumor necrosis factor (TNF-α levels (p<0.05. Thymol and carvacrol reduced interleukin (IL-1β serum and tissue levels, respectively. These components reduced tissue levels of IL-17 from 148.4±13.4pg/ml in CFA-only rats to 90.1±18.9pg/ml (thymol and 82.3±9.2pg/ml (carvacrol. Both components decreased serum IL-17 levels in rats (p<0.05. In comparison, the anti-inflammatory drug, indomethacin, reduced the inflammatory score and decreased tissue TNF-α and IL-1β levels but did not affect IL-17 production. Conclusion: Carvacrol and thymol could relieve inflammation symptoms possibly by downregulating serum and tissue IL-17 expression in addition to key pro-inflammatory cytokines, TNFα and IL-1β.

  13. The protein pheromone Er-1 of the ciliate Euplotes raikovi stimulates human T-cell activity: Involvement of interleukin-2 system

    Energy Technology Data Exchange (ETDEWEB)

    Cervia, Davide, E-mail: d.cervia@unitus.it [Department for Innovation in Biological, Agro-food and Forest systems (DIBAF), University of Tuscia, Viterbo (Italy); Department of Biomedical and Clinical Sciences, “Luigi Sacco” University Hospital, University of Milan, Milano (Italy); Catalani, Elisabetta; Belardinelli, Maria Cristina [Department for Innovation in Biological, Agro-food and Forest systems (DIBAF), University of Tuscia, Viterbo (Italy); Perrotta, Cristiana [Department of Biomedical and Clinical Sciences, “Luigi Sacco” University Hospital, University of Milan, Milano (Italy); Picchietti, Simona [Department for Innovation in Biological, Agro-food and Forest systems (DIBAF), University of Tuscia, Viterbo (Italy); Alimenti, Claudio [Department of Environmental and Natural Sciences, University of Camerino, Camerino (Italy); Casini, Giovanni; Fausto, Anna Maria [Department for Innovation in Biological, Agro-food and Forest systems (DIBAF), University of Tuscia, Viterbo (Italy); Vallesi, Adriana [Department of Environmental and Natural Sciences, University of Camerino, Camerino (Italy)

    2013-02-01

    Water-soluble protein signals (pheromones) of the ciliate Euplotes have been supposed to be functional precursors of growth factors and cytokines that regulate cell–cell interaction in multi-cellular eukaryotes. This work provides evidence that native preparations of the Euplotes raikovi pheromone Er-1 (a helical protein of 40 amino acids) specifically increases viability, DNA synthesis, proliferation, and the production of interferon-γ, tumor necrosis factor-α, interleukin (IL)-1β, IL-2, and IL-13 in human Jurkat T-cells. Also, Er-1 significantly decreases the mRNA levels of the β and γ subunits of IL-2 receptor (IL-2R), while the mRNA levels of the α subunit appeared to be not affected. Jurkat T-cell treatments with Er-1 induced the down-regulation of the IL-2Rα subunit by a reversible and time-dependent endocytosis, and increased the levels of phosphorylation of the extracellular signal-regulated kinases (ERK). The cell-type specificity of these effects was supported by the finding that Er-1, although unable to directly influence the growth of human glioma U-373 cells, induced Jurkat cells to synthesize and release factors that, in turn, inhibited the U-373 cell proliferation. Overall, these findings imply that Er-1 coupling to IL-2R and ERK immuno-enhances T-cell activity, and that this effect likely translates to an inhibition of glioma cell growth. -- Highlights: ► Euplotes pheromone Er-1 increases the growth of human Jurkat T-cells. ► Er-1 increases the T-cell production of specific cytokines. ► Er-1 activates interleukin-2 receptor and extracellular signal-regulated kinases. ► The immuno-enhancing effect of Er-1 on Jurkat cells translates to an inhibition of human glioma cell growth.

  14. Associations of vascular endothelial growth factor (VEGF gene and cytokine (IL-1B, IL-4, IL-6, IL-10, TNFA genes combinations with type 2 diabetes mellitus in women

    Directory of Open Access Journals (Sweden)

    Vladimir Iosifovich Konenkov

    2012-09-01

    Full Text Available Aim. To study the association between vascular endothelial growth factor (VEGF and cytokine (IL1B, IL4, IL6, IL10 and TNFAgene polymorphism combinations with type 2 diabetes mellitus (T2DM in women. Materials and methods. 374 Caucasian women without carbohydrate metabolism disorders from 23 to 68 years of age and 212 womenwith T2DM from 28 to 69 years of age were included in the study. The combinations of polymorphism А-2578С, С+936Т in VEGFgene with polymorphism in IL1B С-31Т, IL4 С-590Т, IL6 G-174C, IL10 A-592C and А-1082G, TNFA А-238G, A-308G and A-863Cwere studied. Results. Analysis revealed 52 combined genetic variations with different rate of occurrence between diabetic and control groups(р

  15. IL-6 and IL-10 levels in the umbilical cord blood of newborns with a history of crack/cocaine exposure in utero: a comparative study

    Directory of Open Access Journals (Sweden)

    Victor Mardini

    2016-03-01

    Full Text Available Introduction Prenatal cocaine exposure (PCE is associated with neurobehavioral problems during childhood and adolescence. Early activation of the inflammatory response may contribute to such changes. Our aim was to compare inflammatory markers (IL-6 and IL-10 both in umbilical cord blood and in maternal peripheral blood at delivery between newborns with history of crack/cocaine exposure in utero and non-exposed newborns. Methods In this cross-sectional study, 57 newborns with a history of crack/cocaine exposure in utero (EN and 99 non-exposed newborns (NEN were compared for IL-6 and IL-10 levels. Sociodemographic and perinatal data, maternal psychopathology, consumption of nicotine and other substances were systematically collected in cases and controls. Results After adjusting for potential confounders, mean IL-6 was significantly higher in EN than in NEN (10,208.54, 95% confidence interval [95%CI] 1,328.54-19,088.55 vs. 2,323.03, 95%CI 1,484.64-3,161.21; p = 0.007; generalized linear model [GLM]. Mean IL-10 was also significantly higher in EN than in NEN (432.22, 95%CI 51.44-812.88 vs. 75.52, 95%CI 5.64-145.39, p = 0.014; GLM. Adjusted postpartum measures of IL-6 were significantly higher in mothers with a history of crack/cocaine use (25,160.05, 95%CI 10,958.15-39,361.99 vs. 8,902.14, 95%CI 5,774.97-12,029.32; p = 0.007; GLM, with no significant differences for IL-10. There was no correlation between maternal and neonatal cytokine levels (Spearman test, p ≥ 0.28 for all measures. Conclusions IL-6 and IL-10 might be early biomarkers of PCE in newborns. These findings could help to elucidate neurobiological pathways underlying neurodevelopmental changes and broaden the range of possibilities for early intervention.

  16. IL-5 promotes induction of antigen-specific CD4+CD25+ T regulatory cells that suppress autoimmunity.

    Science.gov (United States)

    Tran, Giang T; Hodgkinson, Suzanne J; Carter, Nicole M; Verma, Nirupama D; Plain, Karren M; Boyd, Rochelle; Robinson, Catherine M; Nomura, Masaru; Killingsworth, Murray; Hall, Bruce M

    2012-05-10

    Immune responses to foreign and self-Ags can be controlled by regulatory T cells (Tregs) expressing CD4 and IL-2Rα chain (CD25). Defects in Tregs lead to autoimmunity, whereas induction of Ag-specific CD4+CD25+ Tregs restores tolerance. Ag-specific CD4+CD25+ FOXP3+Tregs activated by the T helper type 2 (Th2) cytokine, IL-4, and specific alloantigen promote allograft tolerance. These Tregs expressed the specific IL-5Rα and in the presence of IL-5 proliferate to specific but not third-party Ag. These findings suggest that recombinant IL-5 (rIL-5) therapy may promote Ag-specific Tregs to mediate tolerance. This study showed normal CD4+CD25+ Tregs cultured with IL-4 and an autoantigen expressed Il-5rα. Treatment of experimental autoimmune neuritis with rIL-5 markedly reduced clinical paralysis, weight loss, demyelination, and infiltration of CD4+ (Th1 and Th17) CD8+ T cells and macrophages in nerves. Clinical improvement was associated with expansion of CD4+CD25+FOXP3+ Tregs that expressed Il-5rα and proliferated only to specific autoantigen that was enhanced by rIL-5. Depletion of CD25+ Tregs or blocking of IL-4 abolished the benefits of rIL-5. Thus, rIL-5 promoted Ag-specific Tregs, activated by autoantigen and IL-4, to control autoimmunity. These findings may explain how Th2 responses, especially to parasitic infestation, induce immune tolerance. rIL-5 therapy may be able to induce Ag-specific tolerance in autoimmunity.

  17. Soluble CD163 levels are elevated in cerebrospinal fluid and serum in people with Type 2 diabetes mellitus and are associated with impaired peripheral nerve function

    DEFF Research Database (Denmark)

    Kallestrup, M; Møller, Holger Jon; Tankisi, H

    2015-01-01

    and serum in participants with neuropathy than in those without neuropathy [cerebrospinal fluid: median (range) 131 (86-173) vs 101 (70-190) μg/l, P = 0.08 and serum: 3725 (920-7060) vs 2220 (1130-4780), P = 0.06). CONCLUSIONS: Cerebrospinal fluid soluble CD163 level is associated with impaired peripheral......AIMS: To measure soluble CD163 levels in the cerebrospinal fluid and serum of people with Type 2 diabetes, with and without polyneuropathy, and to relate the findings to peripheral nerve function. METHODS: A total of 22 people with Type 2 diabetes and 12 control subjects without diabetes were...... included in this case-control study. Participants with diabetes were divided into those with neuropathy (n = 8) and those without neuropathy (n = 14) based on clinical examination, vibratory perception thresholds and nerve conduction studies. Serum and cerebrospinal fluid soluble CD163 levels were analysed...

  18. Clinical significance of determination of serum IGF-I and SIL-2R levels in patients with prostatic cancer

    International Nuclear Information System (INIS)

    Zhang Zaigao; Lv Yuliang; Li Jiacheng

    2006-01-01

    Objective: To investigate the significance of changes of serum IGF-I and SIL-2R levels in patients with prostatic cancer. Methods: Serum IGF-I levels (with RIA) and SIL-2R levels (with ELISA) were measured in 31 patients with prostatic cancer and 30 controls. Results: Serum levels of IGF-I and SIL-2R in the 31 patients were significantly higher than those in controls (P<0.01), serum IGF-I and SIL-2R levels were mutually positively correlated (r=0.6182, P<0.01). Conclusion: Serum IGF-I and SIL-2R were useful markers for prostatic cancer. (authors)

  19. IL-4 and IL-13 mediated down-regulation of CD8 expression levels can dampen anti-viral CD8⁺ T cell avidity following HIV-1 recombinant pox viral vaccination.

    Science.gov (United States)

    Wijesundara, Danushka K; Jackson, Ronald J; Tscharke, David C; Ranasinghe, Charani

    2013-09-23

    We have shown that mucosal HIV-1 recombinant pox viral vaccination can induce high, avidity HIV-specific CD8(+) T cells with reduced interleukin (IL)-4 and IL-13 expression compared to, systemic vaccine delivery. In the current study how these cytokines act to regulate anti-viral CD8(+) T, cell avidity following HIV-1 recombinant pox viral prime-boost vaccination was investigated. Out of a panel of T cell avidity markers tested, only CD8 expression levels were found to be enhanced on, KdGag197-205 (HIV)-specific CD8(+) T cells obtained from IL-13(-/-), IL-4(-/-) and signal transducer and, activator of transcription of 6 (STAT6)(-/-) mice compared to wild-type (WT) controls following, vaccination. Elevated CD8 expression levels in this instance also correlated with polyfunctionality, (interferon (IFN)-γ, tumour necorsis factor (TNF)-α and IL-2 production) and the avidity of HIVspecific CD8(+) T cells. Furthermore, mucosal vaccination and vaccination with the novel adjuvanted IL-13 inhibitor (i.e. IL-13Rα2) vaccines significantly enhanced CD8 expression levels on HIV-specific CD8(+), T cells, which correlated with avidity. Using anti-CD8 antibodies that blocked CD8 availability on CD8(+), T cells, it was established that CD8 played an important role in increasing HIV-specific CD8(+) T cell avidity and polyfunctionality in IL-4(-/-), IL-13(-/-) and STAT6(-/-) mice compared to WT controls, following vaccination. Collectively, our data demonstrate that IL-4 and IL-13 dampen CD8 expression levels on anti-viral CD8(+) T cells, which can down-regulate anti-viral CD8(+) T cell avidity and, polyfunctionality following HIV-1 recombinant pox viral vaccination. These findings can be exploited to, design more efficacious vaccines not only against HIV-1, but many chronic infections where high, avidity CD8(+) T cells help protection. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. The insulin receptor substrate-1-related 4PS substrate but not the interleukin-2R gamma chain is involved in interleukin-13-mediated signal transduction.

    Science.gov (United States)

    Wang, L M; Michieli, P; Lie, W R; Liu, F; Lee, C C; Minty, A; Sun, X J; Levine, A; White, M F; Pierce, J H

    1995-12-01

    Interleukin-13 (IL-13) induced a potent mitogenic response in IL-3-dependent TF-1 cells and DNA synthesis to a lesser extent in MO7E and FDC-P1 cells. IL-13 stimulation of these lines, like IL-4 and insulin-like growth factor-1 (IGF-1), resulted in tyrosine phosphorylation of a 170-kD substrate. The tyrosine-phosphorylated 170-kD substrate strongly associated with the 85-kD subunit of phosphoinositol-3 (PI-3) kinase and with Grb-2. Anti-4PS serum readily detected the 170-kD substrate in lysates from both TF-1 and FDC-P1 cells stimulated with IL-13 or IL-4. These data provide evidence that IL-13 induces tyrosine phosphorylation of the 4PS substrate, providing an essential interface between the IL-13 receptor and signaling molecules containing SH2 domains. IL-13 and IL-4 stimulation of murine L cell fibroblasts, which endogenously express the IL-4 receptor (IL-4R alpha) and lack expression of the IL-2 receptor gamma subunit (IL-2R gamma), resulted in tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1)/4PS. Enhanced tyrosine phosphorylation of IRS-1/4PS was observed in response to IL-4, but not IL-13 treatment of L cells transfected with the IL-2R gamma chain. These results indicate that IL-13 does not use the IL-2R gamma subunit in its receptor complex and that expression of IL-2R gamma enhances, but is not absolutely required for mediating IL-4-induced tyrosine phosphorylation of IRS-1/4PS.

  1. Modeling solubility of CO2/hydrocarbon gas in ionic liquid ([emim][FAP]) using Aspen Plus simulations.

    Science.gov (United States)

    Bagchi, Bishwadeep; Sati, Sushmita; Shilapuram, Vidyasagar

    2017-08-01

    The Peng-Robinson equation of state with quadratic van der Waals (vdW) mixing rule model was chosen to perform the thermodynamic calculations in Flash3 column of Aspen Plus to predict the solubility of CO 2 or any one of the hydrocarbons (HCs) among methane, ethane, propane, and butane in an ionic liquid 1-ethyl-3-methylimidazolium tris(pentafluoroethyl)trifluorophosphate ([emim][FAP]). Bubble point pressure, solubility, bubble point temperature, fugacity, and partial molar volume at infinite dilution were obtained from the simulations, and enthalpy of absorption, Gibbs free energy of solvation, and entropy change of absorption were estimated by thermodynamic relations. Results show that carbon chain length has a significant effect on the bubble point pressure. Methane has the highest bubble point pressure among all the considered HCs and CO 2 . The bubble point pressure and fugacity variation with temperature is different for CO 2 as compared to HCs for mole fractions above 0.2. Two different profiles are noticed for enthalpy of absorption when plotted as a function of mole fraction of gas soluble in IL. Partial molar volume of CO 2 decreases with increase in temperature in [emim][FAP], while it is increased for HCs. Bubble point temperature decreases with increase in the mole fraction of the solute. Entropy of solvation increases with temperature till a particular value followed by a decrease with further increase in temperature. Gibbs free energy change of solvation showed that the process of solubility was spontaneous.

  2. Time dependent transition of the levels of protein-conjugated acrolein (PC-Acro), IL-6 and CRP in plasma during stroke.

    Science.gov (United States)

    Yoshida, Madoka; Kato, Naoki; Uemura, Takeshi; Mizoi, Mutsumi; Nakamura, Mizuho; Saiki, Ryotaro; Hatano, Keisuke; Sato, Kunitomo; Kakizaki, Shota; Nakamura, Aya; Ishii, Takuya; Terao, Tohru; Murayama, Yuichi; Kashiwagi, Keiko; Igarashi, Kazuei

    2017-06-01

    Measurement of plasma levels of protein-conjugated acrolein (PC-Acro) together with IL-6 and CRP can be used to identify silent brain infarction (SBI) with high sensitivity and specificity. The aim of this study was to determine how these biomarkers vary during stroke. Levels of PC-Acro, IL-6 and CRP in plasma were measured on day 0, 2, 7 and 14 after the onset of ischemic or hemorrhagic stroke. After the onset of stroke, the level of PC-Acro in plasma was elevated corresponding to the size of stroke. It returned to near control levels by day 2, and remained similar through day 14. The degree of the decrease in PC-Acro on day 2 was greater when the size of brain infarction or hemorrhage was larger. An increase in IL-6 and CRP occurred after the increase in PC-Acro, and it was well correlated with the size of the injury following infarction or hemorrhage. The results suggest that acrolein becomes a trigger for the production of IL-6 and CRP, as previously observed in a mouse model of stroke and in cell culture systems. The increase in IL-6 and CRP was also correlated with poor outcome judging from mRS. The results indicate that the degree of the decrease in PC-Acro and the increase in IL-6 and CRP from day 0 to day 2 was correlated with the size of brain infarction, and the increase in IL-6 and CRP with poor outcome at discharge.

  3. The expression and significance of serum IP-10 and IL-8 in patients with recently diagnosed type 2 diabetes mellitus

    International Nuclear Information System (INIS)

    Feng Zhengui; Yang Shijun

    2005-01-01

    Objective: To investigate the significance of IP-10 and IL-8 in the pathogenesis of type 2 diabetes mellitus (DM2). Methods: The serum levels of IP-10 and IL-8 were measured in 37 patients with recently diagnosed type 2 diabetes mellitus and 33 controls. Results; The serum levels of IP-10 and IL-8 in patients with DM2 were significantly higher than those in controls (P<0.001). Conclusion: The higher levels of IP-10 and IL-8 might play some role in the pathogenesis of DM2. (authors)

  4. Chronic administration of the soluble, nonbacterial fraction of kefir attenuates lipid deposition in LDLr-/- mice.

    Science.gov (United States)

    Santanna, Adriélly F; Filete, Placielle F; Lima, Ewelyne M; Porto, Marcella L; Meyrelles, Silvana S; Vasquez, Elisardo C; Endringer, Denise C; Lenz, Dominik; Abdalla, Dulcineia S P; Pereira, Thiago M C; Andrade, Tadeu U

    2017-03-01

    Kefir is obtained by the action of acidic bacteria and yeasts that exist in symbiotic association in kefir grains. Recently, this fermented milk drink has been recommended for the treatment of several clinical conditions, such as inflammatory, gastrointestinal, or cardiovascular-related diseases, or a combination of these diseases. However, its effects on atherosclerosis are not yet clear. The aim of this study was to prove that chronic treatment with a soluble, nonbacterial fraction of kefir could reduce the progression of atherosclerosis in low-density lipoprotein receptor-deficient (LDLr -/- ) mice. LDLr -/- mice were divided into four groups as follows: RESULTS: The soluble, nonbacterial fraction of kefir reduced lipid deposition (P < 0.05) independent of hypercholesterolemia. Moreover, kefir was capable of diminishing the circulating proinflammatory intereukin (IL)-6 level and the ratio of tumor necrosis factor-α to IL-10 (50% and 42%, P < 0.05, respectively) and augmenting the antiinflammatory IL-10 level by approximately 74% (P < 0.05). Chronic treatment with a soluble nonbacterial fraction of kefir was able to decrease the lipid deposition in LDLr -/- hypercholesteremic mice, at least in part through modifying the circulating cytokine profile. The beneficial effects of kefir provide new perspectives for its use as an adjuvant in the prevention of atherosclerosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Level of Interleukins IL-6 and IL-15 in Blood Plasma of Mice after Forced Swimming Test.

    Science.gov (United States)

    Kapilevich, L V; Kironenko, T A; Zakharova, A N; Kabachkova, A V; Orlov, S N

    2017-05-01

    We measured the concentrations of IL-6 and IL-15 in blood plasma of mice at different terms after forced swimming, taking into account exercise intensity and preliminary training. It was shown that training was an important factor affecting blood plasma level of IL both at rest and after single forced swimming: in trained animals, the concentration of both myokines increased immediately after swimming, while in untrained animals, this increase was observed only after 5 h. Changes in cytokine production against the background of training can be associated with various factors, including neuroendocrine mechanisms, stress, modification of intracellular signaling, as well as reorganization of transcriptional mechanisms in muscle fibers. The most important factor is shift in the ratio of monovalent cations (sodium and potassium) in the cytoplasm.

  6. Effects of quorum sensing system lasR/rhlR gene on the expression of Foxp3, TGF-β1 and IL-10 of lung tissue in tracheal intubation model rat with Pseudomonas aeruginosa biofilm infection

    Directory of Open Access Journals (Sweden)

    Qing-qing XIANG

    2016-03-01

    Full Text Available Objective  To investigate the effects of lasR/rhlR gene on Foxp3, TGF-β1 and IL-10 of lung tissue in rat tracheal intubation model with biofilm infection of Pseudomonas aeruginosa (Ps. aer wild strain (PAO1 and quorum sensing (QS deficient strain (ΔlasRΔrhlR. Methods  Twenty-one SD rats were randomly assigned into 3 groups (7 each: ΔlasRΔrhlR-treated group, PAO1-treated group and sterile control group. Biofilms (BF were cultured in vitro, and the BF coated tube (infected respectively with Ps. aer PAO1 strain, ΔlasRΔrhlR strain, or with asepsis was inserted into the trachea to establish the rat model. The rats were sacrificed on the 7th day after intubation. Colony count of lung tissue homogenate (cfu and lung HE staining were performed, and IL-10 content in bronchoalveolar lavage fluid (BALF, TGF-β1 in lung tissue, and the expression of Foxp3 mRNA in lung cells were determined. Results  The bacterial counts were significantly higher in PAO1 and ΔlasRΔrhlR groups than that in sterile control group, and the counts were obviously higher in PAO1 group (10 400.00±6313.70/g lung tissue than that in ΔlasRΔrhlR group (975.00±559.97/g lung tissue, P<0.05. There was no significant pathological changes in lung tissue in sterile control group, while the bronchi and blood vessels in PAO1 group were infiltrated by a large number of inflammatory cells and complicated with alveolar septum thickening and local abscess and necrosis. The pathological changes were milder in ΔlasRΔrhlR group than in PAO1 group; the expression of Foxp3 mRNA was higher in the two Ps. aer infected groups than that in sterile control group (0.65±0.32, and it was significantly higher in PAO1 group (4.62±1.07 than in ΔlasRΔrhlR group (2.15±1.43, P<0.05. The accumulated optical density value of TGF-β1 was significantly higher in the two Ps. aer infected groups than in sterile control group (3721.66±1412.95, and significantly higher in PAO1 group (65 090.56±33

  7. Predictions of flavonoid solubility in ionic liquids by COSMO-RS: experimental verification, structural elucidation, and solvation characterization

    DEFF Research Database (Denmark)

    Guo, Zheng; Lue, Bena-Marie; Thomsen, Kaj

    2007-01-01

    Predictions of the solubility of flavonoids in a large variety of ionic liquids (ILs) with over 1800 available structures were examined based on COSMO-RS computation. The results show that the solubilities of flavonoids are strongly anion-dependent. Experimental measurement of the solubilities...... of esculin and rutin in 12 ILs with varying anions and cations show that predicted and experimental results generally have a good agreement. Based on the sound physical basis of COSMO-RS, the solubility changes of flavonoids were quantitatively associated with solvation interactions and structural...... characteristics of ILs. COSMO-RS derived parameters, i.e. misfit, H-bonding and van der Waals interaction energy, are shown to be capable of characterizing the complicated multiple interactions in the IL system effectively. H-bonding interaction is the most dominant interaction for ILs (followed by misfit and van...

  8. Significance of post-operative changes of serum IL-18 levels in patients with renal transplantation

    International Nuclear Information System (INIS)

    Qi Falian; Xu Jun; Ke Bingshen; Du Xiumin; Yin Qiuxia; Hu Chengjin

    2005-01-01

    Objective: To study the clinical significance of post-operative changes of serum IL-18 levels in patients after renal transplantation. Methods: Serum IL-18 levels were detected with ELISA in 33 patients with renal transplantation before operation and repeated again on d5, d10 and d20 post-operatively as well as in 35 controls. Results: Pre-operatively, serum IL-18 levels in patients for upcoming renal transplantation were significantly higher than those in controls (P<0.01). After operation, the IL-18 levels on d5 and d10 in patients with acute rejection were not significantly changed from those pre-operatively but were markedly increased on d20 (vs pre-operative, d5, d10; all P<0.01). In the patients without rejection, levels in d5 were significantly higher than those pre-operatively, but dropped to approaching pre-operative values on d10 and d20. On d20, levels of serum IL-18 in patients with rejection were very significantly higher than those in stable patients (P<0.01). Conclusion: Serum IL-18 is a useful marker for identifying acute rejection. (authors)

  9. Elevated levels of serum IL-5 are associated with an increased likelihood of major depressive disorder.

    Science.gov (United States)

    Elomaa, Antti-Pekka; Niskanen, Leo; Herzig, Karl-Heinz; Viinamäki, Heimo; Hintikka, Jukka; Koivumaa-Honkanen, Heli; Honkalampi, Kirsi; Valkonen-Korhonen, Minna; Harvima, Ilkka T; Lehto, Soili M

    2012-01-09

    Inflammatory mediators in both the peripheral circulation and central nervous system (CNS) are dysregulated in major depressive disorder (MDD). Nevertheless, relatively little is known about the role of the T-helper (Th)-2 effector cytokines interleukin (IL)-5 and IL-13 in MDD. We examined the serum levels of these cytokines and a Th-1 comparison cytokine, interferon (IFN)-γ, in 116 individuals (MDD, n = 58; controls, n = 58). In our basic multivariate model controlling for the effects of potential confounders on the associations between MDD and the examined cytokines, each 1-unit increase in the serum IL-5 level increased the likelihood of belonging to the MDD group by 76% (OR 1.76, 95% CI 1.03-2.99, p = 0.04; model covariates: age, gender, marital status, daily smoking and alcohol use). The likelihood further increased in models additionally controlling for the effects of the use of antidepressants and NSAIDS, and a diagnosis of asthma. No such associations were detected with regard to IL-13 (OR 1.08, 95% CI 0.96-1.22, p = 0.22) or IFN-γ (OR 1.02, 95% CI 0.99-1.05, p = 0.23). Elevated levels of IL-5, which uses the neural plasticity-related RAS GTPase-extracellular signal-regulated kinase (Ras-ERK) pathway to mediate its actions in the central nervous system (CNS), could be one of the factors underlying the depression-related changes in CNS plasticity.

  10. Elevated levels of serum IL-5 are associated with an increased likelihood of major depressive disorder

    Directory of Open Access Journals (Sweden)

    Elomaa Antti-Pekka

    2012-01-01

    Full Text Available Abstract Background Inflammatory mediators in both the peripheral circulation and central nervous system (CNS are dysregulated in major depressive disorder (MDD. Nevertheless, relatively little is known about the role of the T-helper (Th-2 effector cytokines interleukin (IL-5 and IL-13 in MDD. Methods We examined the serum levels of these cytokines and a Th-1 comparison cytokine, interferon (IFN-γ, in 116 individuals (MDD, n = 58; controls, n = 58. Results In our basic multivariate model controlling for the effects of potential confounders on the associations between MDD and the examined cytokines, each 1-unit increase in the serum IL-5 level increased the likelihood of belonging to the MDD group by 76% (OR 1.76, 95% CI 1.03-2.99, p = 0.04; model covariates: age, gender, marital status, daily smoking and alcohol use. The likelihood further increased in models additionally controlling for the effects of the use of antidepressants and NSAIDS, and a diagnosis of asthma. No such associations were detected with regard to IL-13 (OR 1.08, 95% CI 0.96-1.22, p = 0.22 or IFN-γ (OR 1.02, 95% CI 0.99-1.05, p = 0.23. Conclusions Elevated levels of IL-5, which uses the neural plasticity-related RAS GTPase-extracellular signal-regulated kinase (Ras-ERK pathway to mediate its actions in the central nervous system (CNS, could be one of the factors underlying the depression-related changes in CNS plasticity.

  11. Azilsartan reduced TNF-α and IL-1β levels, increased IL-10 levels and upregulated VEGF, FGF, KGF, and TGF-α in an oral mucositis model.

    Directory of Open Access Journals (Sweden)

    Aurigena Antunes de Araújo

    Full Text Available Oral mucositis (OM is a common complication of treatments for head and neck cancer, particularly radiotherapy with or without chemotherapy. OM is characterised by oral erythema, ulceration, and pain. The aim of this study was to evaluate the effect of azilsartan (AZT, an angiotensin II receptor antagonist, on 5-fluorouracil (5-FU-induced oral mucositis (OM in Syrian hamsters. OM was induced by the intraperitoneal administration of 5-FU on experimental days 1 (60 mg/Kg and 2 (40 mg/Kg. Animals were pretreated with oral AZT (1, 5, or 10 mg/kg or vehicle 30 min before 5-FU injection and daily until day 10. Experimental treatment protocols were approved by the Animal Ethics Committee Use/CEUA (Number 28/2012 of the UFRN. Macroscopic analysis and cheek pouch samples were removed for histopathologic analysis. Myeloperoxidase (MPO, Malonyldialdehyde (MDA, interleukin-1 beta (IL-1β, interleukin-10 (IL-10, and tumour necrosis factor-alpha (TNF-α were analysed by Enzyme Linked Immuno Sorbent Assay (ELISA. Vascular endothelial growth factor (VEGF, fibroblast growth factor (FGF, keratinocyte growth factor (KGF, and transforming growth factor (TGF-α were measured by immunohistochemistry. Analysis of variance followed by Bonferroni's test was used to calculate the means of intergroup differences (p ≤ 0.05. Treatment with 1 mg/kg AZT reduced levels MPO (p<0.01, MDA (p<0.5 and histological inflammatory cell infiltration, and increased the presence of granulation tissue. AZT treatment at 1 mg/kg reduced the TNF-α (p<0.05 and IL-1β (p<0.05 levels, increased the cheek pouch levels of IL-10 (p<0.01, and upregulated VEGF, FGF, KGF, and TGF-α. Administration of AZT at higher doses (5 and 10 mg/kg did not significantly reverse the OM. AZT at a dose of 1 mg/kg prevented the mucosal damage and inflammation associated with 5-FU-induced OM, increasing granulation and tissue repair.

  12. Lck/PLCγ control migration and proliferation of interleukin (IL)-2-stimulated T cells via the Rac1 GTPase/glycogen phosphorylase pathway.

    Science.gov (United States)

    Llavero, Francisco; Artaso, Alain; Lacerda, Hadriano M; Parada, Luis A; Zugaza, José L

    2016-11-01

    Recently, we have reported that the IL-2-stimulated T cells activate PKCθ in order to phosphorylate the serine residues of αPIX-RhoGEF, and to switch on the Rac1/PYGM pathway resulting in T cell migration and proliferation. However, the molecular mechanism connecting the activated IL-2-R with the PKCθ/αPIX/Rac1/PYGM pathway is still unknown. In this study, the use of a combined pharmacological and genetic approach identified Lck, a Src family member, as the tyrosine kinase phosphorylating PLCγ leading to Rac1 and PYGM activation in the IL-2-stimulated Kit 225 T cells via the PKCθ/αPIX pathway. The PLCγ tyrosine phosphorylation was required to activate first PKCθ, and then αPIX and Rac1/PYGM. The results presented here delineate a novel signalling pathway ranking equally in importance to the three major pathways controlled by the IL-2-R, i.e. PI3K, Ras/MAPK and JAK/STAT pathways. The overall evidence strongly indicates that the central biological role of the novel IL-2-R/Lck/PLCγ/PKCθ/αPIX/Rac1/PYGM signalling pathway is directly related to the control of fundamental cellular processes such as T cell migration and proliferation. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Plasma cytokine profile in tropical endomyocardial fibrosis: predominance of TNF-a, IL-4 and IL-10.

    Directory of Open Access Journals (Sweden)

    Aline S Bossa

    Full Text Available BACKGROUND: The participation of immune/inflammatory mechanisms in the pathogenesis of tropical endomyocardial fibrosis (EMF has been suggested by the finding of early blood and myocardial eosinophilia. However, the inflammatory activation status of late-stage EMF patients is still unknown. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated pro- and anti-inflammatory cytokine levels in plasma samples from late stage EMF patients. Cytokine levels of Tumor Necrosis Factor (TNF-α, Interferon (IFN-γ, Interleukin (IL-2, IL-4, IL-6, and IL-10 were assayed in plasma samples from 27 EMF patients and compared with those of healthy control subjects. All EMF patients displayed detectable plasma levels of at least one of the cytokines tested. We found that TNF-α, IL-6, IL-4, and IL-10 were each detected in at least 74% of tested sera, and plasma levels of IL-10, IL-4, and TNF-α were significantly higher than those of controls. Plasma levels of such cytokines positively correlated with each other. CONCLUSIONS/SIGNIFICANCE: The mixed pro- and anti-inflammatory/Th2circulating cytokine profile in EMF is consistent with the presence of a persistent inflammatory stimulus. On the other hand, the detection of increased levels of TNF-α may be secondary to the cardiovascular involvement observed in these patients, whereas IL-4 and IL-10 may have been upregulated as a homeostatic mechanism to buffer both production and deleterious cardiovascular effects of pro-inflammatory cytokines. Further studies might establish whether these findings play a role in disease pathogenesis.

  14. Association of MiR-126 with Soluble Mesothelin-Related Peptides, a Marker for Malignant Mesothelioma

    Czech Academy of Sciences Publication Activity Database

    Santarelli, L.; Strafella, E.; Staffolani, S.; Amati, M.; Emanuelli, M.; Sartini, D.; Pozzi, V.; Carbonari, D.; Bracci, M.; Pignotti, E.; Mazzanti, P.; Sabbatini, A.; Ranaldi, R.; Gasparini, S.; Neužil, Jiří; Tomasetti, M.

    2011-01-01

    Roč. 6, č. 4 (2011), e18232 E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GA204/08/0811 Institutional research plan: CEZ:AV0Z50520701 Keywords : Malignant pleural mesothelioma * microRNAs * soluble mesothelin-related peptides Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.092, year: 2011

  15. Soluble membrane receptors, interleukin 6, procalcitonin and C reactive protein as prognostic markers in patients with severe sepsis and septic shock.

    Directory of Open Access Journals (Sweden)

    Juan-Jesús Ríos-Toro

    Full Text Available The objective of this study was to explore the diagnostic and prognostic value of soluble triggering receptor expressed on myeloid cell 1 (sTREM-1, soluble cluster of differentiation 14 (sCD14, soluble cluster of differentiation 163 (sCD163, interleukin-6 (IL-6, procalcitonin (PCT, and C-reactive protein (CRP serum levels for patients with severe sepsis and septic shock in an intensive care unit (ICU.Fifty patients admitted at the ICU with the diagnosis of severe sepsis or septic shock were studied. SOFA and APACHE II scores as well as serum biomarkers were measured at days 0, 2 and 5. The influence of these variables on 28-day mortality was analyzed. Twenty healthy individuals served as controls.Baseline serum concentrations of sTREM-1, sCD163, IL-6 and PCT correlated with SOFA score. Only sTREM-1 levels correlated with APACHE II score. The 28-day mortality rate for all patients was 42%. The absence of risk factors for infection, presence of septic shock, baseline values of sCD14 and decrease of PCT and IL-6 from baseline to day 5 were variables associated to mortality in the univariate analysis. The unique independent factor associated to mortality in the multivariate analysis was a decrease of PCT higher than 50% from days 0 to 5.Serum levels of sTREM-1 are correlated with the severity of sepsis. A 50% decrease of PCT was the unique variable associated with survival in the multivariate analysis.

  16. Serum IL-12 Is Increased in Mexican Obese Subjects and Associated with Low-Grade Inflammation and Obesity-Related Parameters

    Directory of Open Access Journals (Sweden)

    K. Suárez-Álvarez

    2013-01-01

    Full Text Available Interleukin-(IL- 12 has been recently suggested to participate during development of insulin resistance in obese mice. Nevertheless, serum IL-12 levels have not been accurately determined in overweight and obese humans. We thus studied serum concentrations of IL-12 in Mexican adult individuals, examining their relationship with low-grade inflammation and obesity-related parameters. A total of 147 healthy individuals, 43 normal weight, 61 overweight, and 43 obese subjects participated in the study. Circulating levels of IL-12, tumor necrosis factor-alpha (TNF-α, leptin, insulin, glucose, total cholesterol, and triglyceride were measured after overnight fasting in all of the study subjects. Waist circumference and body fat percentage were recorded for all the participants. Serum IL-12 was significantly higher in overweight and obese individuals than in normal weight controls. Besides being strongly related with body mass index (r=0.5154, serum IL-12 exhibited a significant relationship with abdominal obesity (r=0.4481, body fat percentage (r=0.5625, serum glucose (r=0.3158, triglyceride (r=0.3714, and TNF-α (r=0.4717. Thus, serum levels of IL-12 are increased in overweight and obese individuals and show a strong relationship with markers of low-grade inflammation and obesity in the Mexican adult population. Further research is needed to understand the role of IL-12 in developing obesity-associated alterations in humans.

  17. Induction of C-Mip by IL-17 Plays an Important Role in Adriamycin-Induced Podocyte Damage

    Directory of Open Access Journals (Sweden)

    Yanbo Liu

    2015-07-01

    Full Text Available Background/Aims: Although the disturbance of T lymphocyte and glomerular podocyte exerts a crucial function in the pathogenesis of proteinuria, the potential link is still unclear. Methods: The balance of Treg and Th17 cells, and the expression of IL-17/IL-17R and c-mip were investigated in adrimycin-induced nephropathy (AN mice. The effect and mechanism of IL-17 on podocyte were explored in cultured podocytes. Results: The proportion of Th17 cells in peripheral blood mononuclear cells, the amount of IL-17 in serum and kidney cortical homogenates, and the expression of IL-17R and c-mip in glomerular podocyte were increased obviously in AN mice. In cultured podocytes, recombinant IL-17 led to an induction of apoptosis and cytoskeletal disorganization, an overproduction of c-mip while down-regulation of phosphor-nephrin, and an increased binding of c-mip to NF-κB/RelA. Silence of c-mip prevented podocyte apoptosis and reduction of phosphor-nephrin by prompting nuclear translocation of NF-κB/RelA in IL-17 treated cells. Persistent activation of NF-κB up-regulated pro-survival protein Bcl-2 and decreased podocyte apoptosis, but had no effect on phosphor-nephrin level. Conclusion: These findings demonstrated that induction of IL-17 released by Th17 cells plays a key role in podocytopathy most likely through down-regulation of phosphor-nephrin and Bcl-2 level via overproduction of c-mip.

  18. No Evidence of Association between Common Autoimmunity STAT4 and IL23R Risk Polymorphisms and Non-Anterior Uveitis

    Science.gov (United States)

    Cordero-Coma, Miguel; Gorroño-Echebarría, Marina Begoña; Fonollosa, Alejandro; Adán, Alfredo; Martínez-Berriotxoa, Agustín; Díaz Valle, David; Pato, Esperanza; Blanco, Ricardo; Cañal, Joaquín; Díaz-Llopis, Manuel; García Serrano, José Luis; de Ramón, Enrique; del Rio, María José; Martín-Villa, José Manuel; Molins, Blanca; Ortego-Centeno, Norberto; Martín, Javier

    2013-01-01

    Objective STAT4 and IL23R loci represent common susceptibility genetic factors in autoimmunity. We decided to investigate for the first time the possible role of different STAT4/IL23R autoimmune disease-associated polymorphisms on the susceptibility to develop non-anterior uveitis and its main clinical phenotypes. Methods Four functional polymorphisms (rs3821236, rs7574865, rs7574070, and rs897200) located within STAT4 gene as well as three independent polymorphisms (rs7517847, rs11209026, and rs1495965) located within IL23R were genotyped using TaqMan® allelic discrimination in a total of 206 patients with non-anterior uveitis and 1553 healthy controls from Spain. Results No statistically significant differences were found when allele and genotype distributions were compared between non-anterior uveitis patients and controls for any STAT4 (rs3821236: P=0.39, OR=1.12, CI 95%=0.87-1.43; rs7574865: P=0.59 OR=1.07, CI 95%=0.84-1.37; rs7574070: P=0.26, OR=0.89, CI 95%=0.72-1.10; rs897200: P=0.22, OR=0.88, CI 95%=0.71-1.08;) or IL23R polymorphisms (rs7517847: P=0.49, OR=1.08, CI 95%=0.87-1.33; rs11209026: P=0.26, OR=0.78, CI 95%=0.51-1.21; rs1495965: P=0.51, OR=0.93, CI 95%=0.76-1.15). Conclusion Our results do not support a relevant role, similar to that described for other autoimmune diseases, of IL23R and STAT4 polymorphisms in the non-anterior uveitis genetic predisposition. Further studies are needed to discard a possible weak effect of the studied variant. PMID:24312163

  19. No evidence of association between common autoimmunity STAT4 and IL23R risk polymorphisms and non-anterior uveitis.

    Science.gov (United States)

    Cénit, María Carmen; Márquez, Ana; Cordero-Coma, Miguel; Gorroño-Echebarría, Marina Begoña; Fonollosa, Alejandro; Adán, Alfredo; Martínez-Berriotxoa, Agustín; Díaz Valle, David; Pato, Esperanza; Blanco, Ricardo; Cañal, Joaquín; Díaz-Llopis, Manuel; García Serrano, José Luis; de Ramón, Enrique; Del Rio, María José; Martín-Villa, José Manuel; Molins, Blanca; Ortego-Centeno, Norberto; Martín, Javier

    2013-01-01

    STAT4 and IL23R loci represent common susceptibility genetic factors in autoimmunity. We decided to investigate for the first time the possible role of different STAT4/IL23R autoimmune disease-associated polymorphisms on the susceptibility to develop non-anterior uveitis and its main clinical phenotypes. Four functional polymorphisms (rs3821236, rs7574865, rs7574070, and rs897200) located within STAT4 gene as well as three independent polymorphisms (rs7517847, rs11209026, and rs1495965) located within IL23R were genotyped using TaqMan® allelic discrimination in a total of 206 patients with non-anterior uveitis and 1553 healthy controls from Spain. No statistically significant differences were found when allele and genotype distributions were compared between non-anterior uveitis patients and controls for any STAT4 (rs3821236: P=0.39, OR=1.12, CI 95%=0.87-1.43; rs7574865: P=0.59 OR=1.07, CI 95%=0.84-1.37; rs7574070: P=0.26, OR=0.89, CI 95%=0.72-1.10; rs897200: P=0.22, OR=0.88, CI 95%=0.71-1.08;) or IL23R polymorphisms (rs7517847: P=0.49, OR=1.08, CI 95%=0.87-1.33; rs11209026: P=0.26, OR=0.78, CI 95%=0.51-1.21; rs1495965: P=0.51, OR=0.93, CI 95%=0.76-1.15). Our results do not support a relevant role, similar to that described for other autoimmune diseases, of IL23R and STAT4 polymorphisms in the non-anterior uveitis genetic predisposition. Further studies are needed to discard a possible weak effect of the studied variant.

  20. No evidence of association between common autoimmunity STAT4 and IL23R risk polymorphisms and non-anterior uveitis.

    Directory of Open Access Journals (Sweden)

    María Carmen Cénit

    Full Text Available OBJECTIVE: STAT4 and IL23R loci represent common susceptibility genetic factors in autoimmunity. We decided to investigate for the first time the possible role of different STAT4/IL23R autoimmune disease-associated polymorphisms on the susceptibility to develop non-anterior uveitis and its main clinical phenotypes. METHODS: Four functional polymorphisms (rs3821236, rs7574865, rs7574070, and rs897200 located within STAT4 gene as well as three independent polymorphisms (rs7517847, rs11209026, and rs1495965 located within IL23R were genotyped using TaqMan® allelic discrimination in a total of 206 patients with non-anterior uveitis and 1553 healthy controls from Spain. RESULTS: No statistically significant differences were found when allele and genotype distributions were compared between non-anterior uveitis patients and controls for any STAT4 (rs3821236: P=0.39, OR=1.12, CI 95%=0.87-1.43; rs7574865: P=0.59 OR=1.07, CI 95%=0.84-1.37; rs7574070: P=0.26, OR=0.89, CI 95%=0.72-1.10; rs897200: P=0.22, OR=0.88, CI 95%=0.71-1.08; or IL23R polymorphisms (rs7517847: P=0.49, OR=1.08, CI 95%=0.87-1.33; rs11209026: P=0.26, OR=0.78, CI 95%=0.51-1.21; rs1495965: P=0.51, OR=0.93, CI 95%=0.76-1.15. CONCLUSION: Our results do not support a relevant role, similar to that described for other autoimmune diseases, of IL23R and STAT4 polymorphisms in the non-anterior uveitis genetic predisposition. Further studies are needed to discard a possible weak effect of the studied variant.

  1. miR-122 targets NOD2 to decrease intestinal epithelial cell injury in Crohn’s disease

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yu; Wang, Chengxiao; Liu, Ying; Tang, Liwei; Zheng, Mingxia [Department of Pediatrics, Jiangwan Hospital of Shanghai, Shanghai 200434 (China); Xu, Chundi [Department of Pediatrics, Ruijin affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200025 (China); Song, Jian, E-mail: jiansongkxy@126.com [Department of Gastroenterology, Jiangwan Hospital of Shanghai, Shanghai 200434 (China); Meng, Xiaochun [Department of Pediatrics, Jiangwan Hospital of Shanghai, Shanghai 200434 (China)

    2013-08-16

    Highlights: •NOD2 is a target gene of miR-122. •miR-122 inhibits LPS-induced apoptosis by suppressing NOD2 in HT-29 cells. •miR-122 reduces the expression of pro-inflammatory cytokines (TNF-α and IFN-γ). •miR-122 promotes the release of anti-inflammatory cytokines (IL-4 and IL-10). •NF-κB signaling pathway is involved in inflammatory response induced by LPS. -- Abstract: Crohn’s disease (CD) is one of the two major types of inflammatory bowel disease (IBD) thought to be caused by genetic and environmental factors. Recently, miR-122 was found to be deregulated in association with CD progression. However, the underlying molecular mechanisms remain unclear. In the present study, the gene nucleotide-binding oligomerization domain 2 (NOD2/CARD15), which is strongly associated with susceptibility to CD, was identified as a functional target of miR-122. MiR-122 inhibited LPS-induced apoptosis by suppressing NOD2 in HT-29 cells. NOD2 interaction with LPS initiates signal transduction mechanisms resulting in the activation of nuclear factor κB (NF-κB) and the stimulation of downstream pro-inflammatory events. The activation of NF-κB was inhibited in LPS-stimulated HT-29 cells pretreated with miR-122 precursor or NOD2 shRNA. The expression of the pro-inflammatory cytokines TNF-α and IFN-γ was significantly decreased, whereas therelease of the anti-inflammatory cytokines IL-4 and IL-10 was increased in LPS-stimulated HT-29 cells pretreated with miR-122 precursor, NOD2 shRNA or the NF-κB inhibitor QNZ. Taken together, these results indicate that miR-122 and its target gene NOD2 may play an important role in the injury of intestinal epithelial cells induced by LPS.

  2. Cytokines, cytokine antagonists, and soluble adhesion molecules in pediatric OMS and other neuroinflammatory disorders.

    Science.gov (United States)

    Pranzatelli, Michael R; Tate, Elizabeth D; McGee, Nathan R; Colliver, Jerry A

    2013-03-15

    To test for hypothesized disease- and treatment-induced changes in cytokines and adhesion molecules in children with opsoclonus-myoclonus syndrome (OMS). Multiplex bead assay technology was used for simultaneous measurement of 34 soluble cytokines in cerebrospinal fluid (CSF) and serum. Soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) were measured by ELISA. In total, there were 388 children (239 OMS, 114 controls, and 35 other inflammatory neurological disorders (OIND)). In untreated OMS, mean CSF IL-6 was elevated 2.3-fold, but 67-fold in OIND, without significant differences in other CSF cytokines. Mean serum concentrations of sIL-2Ra (+50%) and CXCL1 (+70%) (pOMS than controls (p=0.005), as was serum CCL11 and IL-13 in treated OMS. Mean CSF CCL4 and IL-1Ra were selectively higher in IVIg-treated OMS (p≤0.0001). CSF sICAM-1 was elevated only in OIND (3.3-fold); serum sICAM-1 was higher in untreated OMS (+21%); and sVCAM-1 was not affected. No correlations with OMS severity or duration were identified. Novel cytokine, cytokine antagonist, and soluble adhesion molecule abnormalities due to OMS or treatment were found. However, the normality of much of the data strengthens previous findings implicating B cell mechanisms. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans

    DEFF Research Database (Denmark)

    Steensberg, Adam; Fischer, Christian Philip; Keller, Charlotte

    2003-01-01

    compared with saline infusion. In addition, C-reactive protein increased 3 h post-rhIL-6 infusion and was further elevated 16 h later compared with saline infusion. rhIL-6 induced increased levels of plasma cortisol and, consequently, an increase in circulating neutrophils and a decrease in the lymphocyte......-alpha, enhances the levels not only of IL-1ra but also of IL-10. Furthermore, IL-6 induces an increase in cortisol and, consequently, in neutrocytosis and late lymphopenia to the same magnitude and with the same kinetics as during exercise, suggesting that muscle-derived IL-6 has a central role in exercise...

  4. Anti-Inflammatory (IL-10 Levels and Affects the Survival of Prostate Carcinoma Patients: An Explorative Study in North Indian Population

    Directory of Open Access Journals (Sweden)

    Shailendra Dwivedi

    2014-01-01

    Full Text Available Objective. Inflammation is an important hallmark of all cancers and net inflammatory response is determined by a delicate balance between pro- and anti-inflammatory cytokines, which may be affected by tobacco exposure, so the present study was designed to explore the effect of various modes of tobacco exposure on interleukin-12 (IL-12 and interleukin-10 (IL-10 inflammatory cytokine levels and survival in prostate carcinoma (PCa patients. Methods. 285 cancer patients and equal controls with 94 BPH (benign prostatic hyperplasia were recruited; baseline levels of serum IL-12 and IL-10 were measured and analyzed in various tobacco exposed groups by appropriate statistical tool. Five-year survivals of patients were analyzed by Log-rank (Mantel-Cox test (graph pad version 5. Results. The expression of serum proinflammatory (IL-12 and anti-inflammatory (IL-10 cytokines was correlated with tobacco exposed group as smokers, chewers, and alcohol users have shown significantly higher levels (P<0.001 with significantly lower median survivals (27.1 months, standard error = 2.86, and 95% CI: 21.4–32.62; than nonusers. Stages III and IV of tobacco addicted patients have also shown significantly increased levels of IL-12 and IL-10. Conclusions. IL-12 and IL-10 seem to be affected by various modes of tobacco exposure and inflammation also affects median survival of cancer patients.

  5. IL-4 enhances IL-10 production in Th1 cells: implications for Th1 and Th2 regulation.

    Science.gov (United States)

    Mitchell, Ruth E; Hassan, Masriana; Burton, Bronwen R; Britton, Graham; Hill, Elaine V; Verhagen, Johan; Wraith, David C

    2017-09-12

    IL-10 is an immunomodulatory cytokine with a critical role in limiting inflammation in immune-mediated pathologies. The mechanisms leading to IL-10 expression by CD4 + T cells are being elucidated, with several cytokines implicated. We explored the effect of IL-4 on the natural phenomenon of IL-10 production by a chronically stimulated antigen-specific population of differentiated Th1 cells. In vitro, IL-4 blockade inhibited while addition of exogenous IL-4 to Th1 cultures enhanced IL-10 production. In the in vivo setting of peptide immunotherapy leading to a chronically stimulated Th1 phenotype, lack of IL-4Rα inhibited the induction of IL-10. Exploring the interplay of Th1 and Th2 cells through co-culture, Th2-derived IL-4 promoted IL-10 expression by Th1 cultures, reducing their pathogenicity in vivo. Co-culture led to upregulated c-Maf expression with no decrease in the proportion of T-bet + cells in these cultures. Addition of IL-4 also reduced the encephalitogenic capacity of Th1 cultures. These data demonstrate that IL-4 contributes to IL-10 production and that Th2 cells modulate Th1 cultures towards a self-regulatory phenotype, contributing to the cross-regulation of Th1 and Th2 cells. These findings are important in the context of Th1 driven diseases since they reveal how the Th1 phenotype and function can be modulated by IL-4.

  6. Association between lower frequency of R381Q variant (rs11209026) in IL-23 receptor gene and increased risk of recurrent spontaneous abortion (RSA).

    Science.gov (United States)

    Abdollahi, Elham; Tavasolian, Fataneh; Ghasemi, Nasrin; Mirghanizadeh, Seyed Ali; Azizi, Mohammdareza; Ghoryani, Mohsen; Samadi, Morteza

    2015-01-01

    Recurrent spontaneous abortion (RSA) is defined as three or more consecutive spontaneous abortions before the 20th week of gestation. The purpose of the present study was to investigate the association between a functional single nucleotide polymorphism (SNP) in the interleukin (IL)-23 receptor gene (IL-23R; rs11209026, 1142 G wild type → A reduced function, Arg381Gln, R381Q) and RSA. For the study, 200 RSA patients (confirmed using established diagnostic criteria) and 200 normal individuals in fertility and infertility centers in the cities of Yazd and Isfahan were recruited during a period from 2012-2013. Using PCR-RFLP, the R381Q variant was screened for in the IL-23R gene of the patients and controls. The results indicated there were significant differences in the frequency of this genetic variant in the patients versus the healthy controls, i.e. 2% and 7.5%, respectively (p value = 0.01; odds ratio = 0.25; CI = 95%). No significant difference was found for the G allelic frequency in patients with RSA and in the control group (p = 0.60). The A allelic frequency was significantly different between the two groups (p = 0.01). Based on these findings, it is concluded that the frequency of single nucleotide polymorphism in the IL-23 receptor (R381Q) in patients with recurrent spontaneous abortion (RSA) is less than that found in normal control women.

  7. Faut-il réformer la caisse de compensation au Maroc ?

    OpenAIRE

    Tarbalouti, Mr

    2014-01-01

    Faut-il réformer la caisse de compensation au Maroc? Par Essaid Tarbalouti Version, Mars 2014 The debate on the efficiency of the subsidy of the prices of foodstuffs granted by the policy of compensation and his reform are deeply livened up between the government and the opposition in terms of its cost and its ineffectiveness. This debate concentrate on the social earnings to replace this mechanism of assistant by the granting of a minimum income to the poor people. We...

  8. Evaluation of inflammatory markers interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9) in asthma.

    Science.gov (United States)

    Naik, Srilata Puru; P A, Mahesh; B S, Jayaraj; Madhunapantula, SubbaRao V; Jahromi, Sarah Raeiszadeh; Yadav, Manish Kumar

    2017-08-01

    Even though IL-6 and MMP-9 are associated with airway inflammation in asthma, there is paucity of data in Indian population. To determine the levels of IL-6 and MMP-9 in the serum of patients suffering from asthma, and correlate with (a) disease severity, as per GINA guidelines; (b) clinical phenotypes; and (c) response to treatment. The levels of IL-6 and MMP-9 were compared between moderate persistent asthma (n = 25), severe persistent asthma (n = 25) and normal controls (n = 30). IL-6 and MMP-9 were measured by ELISA (R&D Systems Inc., USA and Canada) and compared between controls and asthmatics and between groups of different asthma severity, clinical variables, spirometry, and allergen sensitization. Spirometry was repeated after 2 months of ICS+LABA to assess response to treatment in relation to baseline IL-6 and MMP-9 levels. We observed a significant difference in both IL-6 and MMP-9 levels among asthmatics versus controls (p asthma (p asthma duration, total IgE, AEC, number of allergens sensitized and degree of sensitization. No significant correlation (p > 0.5) was observed with IL-6 and MMP-9 levels and FEV 1 improvement after 2 months of ICS+LABA. Higher levels of IL-6 and MMP-9 were observed in asthmatics as compared to controls and in severe persistent asthma as compared to moderate persistent asthma, higher levels of MMP-9 was associated with lower lung functions.

  9. Second-trimester IL-15 and IL-18 levels in the amniotic fluid of fetuses with normal karyotypes and with chromosome abnormalities.

    Science.gov (United States)

    Klimkiewicz-Blok, Dominika; Florjański, Jerzy; Zalewski, Jerzy; Blok, Radosław

    2012-01-01

    Little is known about the behavior of interleukin 15 (IL-15) and 18 (IL-18) in the amniotic fluid in the second trimester of gestations complicated by chromosomal defects in the fetus. Likewise, it has not yet been established whether a fetus with chromosome abnormalities creates its immunity mechanisms in the same way as a fetus with a normal karyotype. The aim of this work was to assess the concentration of IL-15 and IL-18 in the amniotic fluid in the second trimester of gestation in fetuses with normal karyotypes and with chromosome abnormalities. The material consisted of 51 samples of amniotic fluid obtained from genetic amniocenteses carried out between the 15th and the 19th weeks of gestation. On the basis of cytogenetic screening, two groups were singled out: Group I--45 fetuses with normal karyotypes, and Group II--6 fetuses with abnormal karyotypes. The concentrations of IL-15 and IL-18 in the amniotic fluid were assessed with ready-made assays and analyzed, and the results from both groups were compared. The differences between the IL-15 levels in the amniotic fluid from Groups I and II proved to be statistically insignificant (p = 0.054). However, the average IL-18 levels in the amniotic fluid of the fetuses with normal karyotypes were significantly higher than in the amniotic fluid of the fetuses with chromosome abnormalities (p = 0.032). Some defense mechanisms in the second trimester of gestation in fetuses with chromosome abnormalities may develop in a different way than in fetuses with normal karyotypes.

  10. Th-17 regulatory cytokines IL-21, IL-23, and IL-6 enhance neutrophil production of IL-17 cytokines during asthma.

    Science.gov (United States)

    Halwani, Rabih; Sultana, Asma; Vazquez-Tello, Alejandro; Jamhawi, Amer; Al-Masri, Abeer A; Al-Muhsen, Saleh

    2017-11-01

    In a subset of severe asthma patients, chronic airway inflammation is associated with infiltration of neutrophils, Th-17 cells and elevated expression of Th-17-derived cytokines (e.g., interleukin [IL]-17, IL-21, IL-22). Peripheral neutrophils from allergic asthmatics are known to express higher IL-17 cytokine levels than those from healthy subjects, but the regulatory mechanisms involved are not well understood. We hypothesize that Th-17 regulatory cytokines could modulate IL-17 expression in neutrophils. Peripheral blood neutrophils isolated from asthmatics were stimulated with IL-21, IL-23, and IL-6 cytokines and their ability to produce IL-17A and IL-17F was determined relative to healthy controls. Signal transducer and activator of transcription 3 (STAT3) phosphorylation levels were measured in stimulated neutrophil using flow cytometry. The requirement for STAT3 phosphorylation was determined by blocking its activation using a specific chemical inhibitor. Stimulating asthmatic neutrophils with IL-21, 23, and 6 enhanced the production of IL-17A and IL-17F at significantly higher levels comparatively to healthy controls. Stimulating neutrophils with IL-21, IL-23, and IL-6 cytokines enhanced STAT3 phosphorylation, in all cases. Interestingly, inhibiting STAT3 phosphorylation using a specific chemical inhibitor dramatically blocked the ability of neutrophils to produce IL-17, demonstrating that STAT3 activation is the major factor mediating IL-17 gene expression. These findings suggest that neutrophil infiltration in lungs of severe asthmatics may represent an important source of pro-inflammatory IL-17A and -F cytokines, a production enhanced by Th-17 regulatory cytokines, and thus providing a feedback mechanism that sustains inflammation. Our results suggest that STAT3 pathway could be a potential target for regulating neutrophilic inflammation during severe asthma.

  11. The changes of IL-8, IL-10, IL-12 and IgE in serum of patients with asthma

    International Nuclear Information System (INIS)

    Zhang Chao; Liu Deyi; Hou Guihua; Wang Haodan

    2002-01-01

    To evaluate the relationship and the clinical significance between the serum IL-8, IL-10, IL-12 and IgE in patients with asthma, the serum IL-8, IL-10 are measured by radioimmunoassay method and the serum IL-12, IgE by ELISA in 55 patients with asthma. The level of serum IL-8, IgE at stage of episode are significantly higher than that at stage of remission (P<0.01); the level of serum IL-10, IL-12 at stage of episode are significantly lower than that at stage of remission (P<0.01). Linear regression shows that the decrease of IL-12 relate to the increase of IgE. The results suggests that the change of the level of serum IL-8, IL-10, IL-12 and IgE could be a maker for the aggravation of asthma

  12. Increased levels of CCR7(lo)PD-1(hi) CXCR5+ CD4+ T cells, and associated factors Bcl-6, CXCR5, IL-21 and IL-6 contribute to repeated implantation failure.

    Science.gov (United States)

    Gong, Qiaoqiao; Zhu, Yuejie; Pang, Nannan; Ai, Haiquan; Gong, Xiaoyun; La, Xiaolin; Ding, Jianbing

    2017-12-01

    In vitro fertilization-embryo transfer (IVF-ET) can be used by infertile couples to assist with reproduction; however, failure of the embryo to implant into the endometrial lining results in failure of the IVF treatment. The present study investigated the expression of chemokine receptor 7 (CCR7)(lo) programmed death-1(PD-1)(hi) chemokine receptor type 5 (CXCR5) + cluster of differentiation 4 (CD4) + T cells and associated factors in patients with repeated implantation failure (RIF). A total of 30 females with RIF and 30 healthy females were enrolled in the current study. Flow cytometry was used to detect the proportion of CCR7(lo)PD-1(hi) CXCR5 + CD4 + T cells in the peripheral blood. Cytokine bead arrays were performed to detect the levels of interleukin (IL)-6, -4 and -2 in the serum. ELISAs were used to detect the level of IL-21 in the serum. Quantitative real time polymerase chain reaction analysis and immunohistochemistry were used to investigate the expression of B-cell lymphoma 6 (Bcl-6), chemokine receptor type 5 (CXCR5) and IL-21 in the endometrium. The results revealed that the percentage of CCR7(lo)PD-1(hi) CXCR5 + CD4 + T cells was increased in the RIF group compared with the control group during the mid luteal phase. The mRNA and protein levels of Bcl-6, IL-21 and CXCR5 in the endometrium and the concentrations of IL-21 and IL-6 in the serum were significantly increased in the RIF group; however, no significant difference was observed between the two groups in regards to the expression of IL-4 and IL-2. Furthermore, a significant positive correlation was identified between the percentage of CCR7(lo)PD-1(hi) CXCR5 + CD4 + T cells and IL-21 and IL-6 levels. The expression of IL-21 also had a positive correlation with Bcl-6 and CXCR5 expression in the RIF group. These results suggest that increased levels of CCR7(lo)PD-1(hi) CXCR5 + CD4 + T cells and associated factors contribute to RIF and could therefore be a potential therapeutic target.

  13. Human osteoarthritic cartilage shows reduced in vivo expression of IL-4, a chondroprotective cytokine that differentially modulates IL-1β-stimulated production of chemokines and matrix-degrading enzymes in vitro.

    Directory of Open Access Journals (Sweden)

    Elisa Assirelli

    Full Text Available BACKGROUND: In osteoarthritis (OA, an inflammatory environment is responsible for the imbalance between the anabolic and catabolic activity of chondrocytes and, thus, for articular cartilage derangement. This study was aimed at providing further insight into the impairment of the anabolic cytokine IL-4 and its receptors in human OA cartilage, as well as the potential ability of IL-4 to antagonize the catabolic phenotype induced by IL-1β. METHODOLOGY/PRINCIPAL FINDINGS: The in vivo expression of IL-4 and IL-4 receptor subunits (IL-4R, IL-2Rγ, IL-13Rα1 was investigated on full thickness OA or normal knee cartilage. IL-4 expression was found to be significantly lower in OA, both in terms of the percentage of positive cells and the amount of signal per cell. IL-4 receptor type I and II were mostly expressed in mid-deep cartilage layers. No significant difference for each IL-4 receptor subunit was noted. IL-4 anti-inflammatory and anti-catabolic activity was assessed in vitro in the presence of IL-1β and/or IL-4 for 24 hours using differentiated high density primary OA chondrocyte also exhibiting the three IL-4 R subunits found in vivo. Chemokines, extracellular matrix degrading enzymes and their inhibitors were evaluated at mRNA (real time PCR and protein (ELISA or western blot levels. IL-4 did not affect IL-1β-induced mRNA expression of GRO-α/CXCL1, IL-8/CXCL8, ADAMTS-5, TIMP-1 or TIMP-3. Conversely, IL-4 significantly inhibited RANTES/CCL5, MIP-1α/CCL3, MIP-1β/CCL4, MMP-13 and ADAMTS-4. These results were confirmed at protein level for RANTES/CCL5 and MMP-13. CONCLUSIONS/SIGNIFICANCE: Our results indicate for the first time that OA cartilage has a significantly lower expression of IL-4. Furthermore, we found differences in the spectrum of biological effects of IL-4. The findings that IL-4 has the ability to hamper the IL-1β-induced release of both MMP-13 and CCL5/RANTES, both markers of OA chondrocytes, strongly indicates IL-4 as a

  14. Expression of SCM-1alpha/lymphotactin and SCM-1beta in natural killer cells is upregulated by IL-2 and IL-12.

    Science.gov (United States)

    Hennemann, B; Tam, Y K; Tonn, T; Klingemann, H G

    1999-07-01

    Recruitment of lymphocytes is an important feature of the host immune response against pathogens. However, the mechanisms by which lymphocytes are attracted are not yet fully understood. Recently, the cDNA of a lymphocyte-specific chemokine, lymphotactin (Lptn), was isolated from murine and human T cells and was also found to be expressed in murine NK cells and human NK cell clones. This study investigated the influence of interleukin (IL)-2 and IL-12 on the expression of Lptn, also known as SCM (single cysteine motif)-1alpha, and SCM-1beta, a 97% homolog of Lptn, in freshly isolated human NK cells and the human NK cell line NK-92. Northern blot analysis and RT-PCR confirmed that nonactivated human NK cells expressed both genes at low level. After activation with IL-2 or IL-12, the expression of both Lptn and SCM-1beta was upregulated within hours. NK-92 cells maintained in medium supplemented with IL-2 constitutively expressed SCM-1 mRNA. However, after 24 h of IL-2 starvation and subsequent culturing at various IL-2 concentrations, the expression of Lptn/SCM-1alpha was upregulated in a dose-dependent manner, whereas the expression of SCM-1beta remained consistently high. These observations indicate that NK cells, in addition to T lymphocytes, express Lptn/SCM-1alpha and SCM-1beta after cytokine activation. The upregulation of these chemokines in NK cells on activation likely acts to increase the number of effector cells reaching the site of an immune response such as inflammation.

  15. Differential Cytokine Changes in Patients with Myasthenia Gravis with Antibodies against AChR and MuSK.

    Directory of Open Access Journals (Sweden)

    Vuslat Yilmaz

    Full Text Available Neuromuscular transmission failure in myasthenia gravis (MG is most commonly elicited by autoantibodies (ab to the acetylcholine receptor or the muscle-specific kinase, constituting AChR-MG and MuSK-MG. It is controversial whether these MG subtypes arise through different T helper (Th 1, Th2 or Th17 polarized immune reactions and how these reactions are blunted by immunosuppression. To address these questions, plasma levels of cytokines related to various Th subtypes were determined in patients with AChR-MG, MuSK-MG and healthy controls (CON. Peripheral blood mononuclear cells (PBMC were activated in vitro by anti-CD3, and cytokines were quantified in supernatants. In purified blood CD4+ T cells, RNA of various cytokines, Th subtype specific transcription factors and the co-stimulatory molecule, CD40L, were quantified by qRT-PCR. Plasma levels of Th1, Th2 and Th17 related cytokines were overall not significantly different between MG subtypes and CON. By contrast, in vitro stimulated PBMC from MuSK-MG but not AChR-MG patients showed significantly increased secretion of the Th1, Th17 and T follicular helper cell related cytokines, IFN-γ, IL-17A and IL-21. Stimulated expression of IL-4, IL-6, IL-10 and IL-13 was not significantly different. At the RNA level, expression of CD40L by CD4+ T cells was reduced in both AChR-MG and MuSK-MG patients while expression of Th subset related cytokines and transcription factors were normal. Immunosuppression treatment had two effects: First, it reduced levels of IL12p40 in the plasma of AChR-MG and MuSK-MG patients, leaving other cytokine levels unchanged; second, it reduced spontaneous secretion of IFN-γ and increased secretion of IL-6 and IL-10 by cultured PBMC from AChR-MG, but not MuSK-MG patients. We conclude that Th1 and Th17 immune reactions play a role in MuSK-MG. Immunosuppression attenuates the Th1 response in AChR-MG and MuSK-MG, but otherwise modulates immune responses in AChR-MG and Mu

  16. Circulating cytokines and cytokine receptors in infliximab treatment failure due to TNF-α independent Crohn disease

    DEFF Research Database (Denmark)

    Steenholdt, Casper; Coskun, Mehmet; Buhl, Sine

    2016-01-01

    -IFX antibodies. Circulating cytokines and cytokine receptors were assessed by enzyme-linked immunosorbent assay: granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin (IL)-1α, IL-1β, IL-1Ra, IL-6, IL-10, IL-12p70, soluble TNF receptor (sTNF-R) 1, sTNF-R2, IL-17A, and monocyte chemotactic...

  17. CO2 Capture and Separation Properties in the Ionic Liquid 1-n-Butyl-3-Methylimidazolium Nonafluorobutylsulfonate

    Directory of Open Access Journals (Sweden)

    Lingyun Zhou

    2014-05-01

    Full Text Available Recently, the use of ionic liquids (ILs for carbon capture and separation processes has gained great interest by many researchers due to the high solubility of CO2 in ILs. In the present work, solubility measurements of CO2 in the novel IL 1-n-butyl-3-methylimidazolium nonafluorobutylsulfonate [C4mim][CF3CF2CF2CF2SO3] were performed with a high-pressure view-cell technique in the temperature range from 293.15 to 343.15 K and pressures up to about 4.2 MPa. For comparison, solubilities of H2, N2, and O2 in the IL were also measured at 323.15 K via the same procedure. The Krichevsky-Kasarnovsky equation was employed to correlate the measured solubility data. Henry’s law constants, enthalpies, and entropies of absorption for CO2 in the IL were also determined and presented. The CO2 solubility in this IL was compared with other ILs sharing the same cation. It was shown that the solubility of CO2 in these ILs follows the sequence: [C4mim][CF3CF2CF2CF2SO3] ≈ [C4mim][Tf2N] > [C4mim][CF3CF2CF2COO] > [C4mim][BF4], and the solubility selectivity of CO2 relative to O2, N2, and H2 in [C4mim][CF3CF2CF2CF2SO3] was 8, 16, and 22, respectively. Furthermore, this IL is regenerable and exhibits good stability. Therefore, the IL reported here would be a promising sorbent for CO2.

  18. IL-8 dictates glycosaminoglycan binding and stability of IL-18 in cystic fibrosis.

    LENUS (Irish Health Repository)

    Reeves, Emer P

    2010-02-01

    Dysregulation of airway inflammation contributes to lung disease in cystic fibrosis (CF). Inflammation is mediated by inflammatory cytokines, including IL-8, which illustrates an increase in biological half-life and proinflammatory activity when bound to glycosaminoglycans (GAGs). The aim of this project was to compare IL-8 and IL-18 for their relative stability, activity, and interaction with GAGs, including chondroitin sulfate, hyaluronic acid, and heparan sulfate, present in high quantities in the lungs of patients with CF. Bronchoalveolar lavage fluid was collected from patients with CF (n = 28), non-CF controls (n = 14), and patients with chronic obstructive pulmonary disease (n = 12). Increased levels of IL-8 and reduced concentrations of IL-18 were detected in bronchial samples obtained from CF individuals. The low level of IL-18 was not a defect in IL-18 production, as the pro- and mature forms of the molecule were expressed and produced by CF epithelial cells and monocytes. There was, however, a marked competition between IL-8 and IL-18 for binding to GAGs. A pronounced loss of IL-18 binding capacity occurred in the presence of IL-8, which displaced IL-18 from these anionic-matrices, rendering the cytokine susceptible to proteolytic degradation by neutrophil elastase. As a biological consequence of IL-18 degradation, reduced levels of IL-2 were secreted by Jurkat T lymphocytes. In conclusion, a novel mechanism has been identified highlighting the potential of IL-8 to determine the fate of other inflammatory molecules, such as IL-18, within the inflammatory milieu of the CF lung.

  19. Hypertension in Obese Type 2 Diabetes Patients is Associated with Increases in Insulin Resistance and IL-6 Cytokine Levels: Potential Targets for an Efficient Preventive Intervention

    Directory of Open Access Journals (Sweden)

    Ljiljana Lukic

    2014-03-01

    Full Text Available Increased body weight as well as type 2 diabetes (T2D are found to be associated with increased incidence of hypertension, although the mechanisms facilitating hypertension in T2D or nondiabetic individuals are not clear. Therefore, in this study we compared the levels of insulin resistance (IR:OGIS, plasma insulin (PI:RIA levels, and pro-inflammatory cytokines (IL-6 and TNF-α: ELISA, being risk factors previously found to be associated with hypertension, in T2D patients showing increased body weight (obese and overweight, BMI ≥ 25 kg/m2 with hypertension (group A, N = 30, or without hypertension (group B, N = 30, and in nonobese (BMI < 25 kg/m2, normotensive controls (group C, N = 15. We found that OGIS index was the lowest (A: 267 ± 35.42 vs. B: 342.89 ± 32.0, p < 0.01 and PI levels were the highest (A: 31.05 ± 8.24 vs. B: 17.23 ± 3.23, p < 0.01 in group A. In addition, IL-6 levels were higher in group A (A: 15.46 ± 5.15 vs. B: 11.77 ± 6.09; p < 0.05 while there was no difference in TNF-α levels. Our results have shown that appearance of hypertension in T2D patients with increased body weight was dependent on further increase in IR which was associated with the rise in pro-inflammatory IL-6 cytokine. The results imply that lifestyle intervention aimed to decrease IR might be beneficial in reducing the risk for hypertension in those T2D individuals.

  20. Relation of zinc levels and water soluble phosphorus in suphala [fertilizer] on uptake of phosphorus and zinc

    International Nuclear Information System (INIS)

    Mutatkar, V.K.; Chapke, V.G.

    1975-01-01

    Under pot culture, four levels of Zn 0, 2, 4 and 6 ppm, were studied in relation to 30, 50 and 100 % water soluble levels of phosphorus in suphala for the dry matter production and uptake of P and Zn by maize on acidic soil of Goa and black cotton soil of Maharashtra. 32 P and 65 Zn tracers were used for this investigation. The results revealed that application of Zn has increased the dry matter and uptake of phosphorus upto 4 ppm of Zn application and it has decreased at 6 ppm Zn level. This inhibition of P uptake was observed at all water soluble levels of P and in both the soils studied. Zn uptake by maize in both the soils under study was increased with increasing level of Zn, irrespective of water soluble level of P in suphala. (author)

  1. Factors Associated With Plasma IL-6 Levels During HIV Infection

    DEFF Research Database (Denmark)

    Borges, Álvaro H; O'Connor, Jemma L; Phillips, Andrew N

    2015-01-01

    (Strategies for Management of Anti-Retroviral Therapy) trial, CD4/CD8 ratio, smoking, comorbid conditions, serum lipids, renal function (estimated glomerular filtration rate [eGFR]), and educational level were assessed. RESULTS: Demographics associated with higher IL-6 levels were older age and lower...

  2. Human Langerhans cells use an IL-15R-α/IL-15/pSTAT5-dependent mechanism to break T-cell tolerance against the self-differentiation tumor antigen WT1.

    Science.gov (United States)

    Romano, Emanuela; Cotari, Jesse W; Barreira da Silva, Rosa; Betts, Brian C; Chung, David J; Avogadri, Francesca; Fink, Mitsu J; St Angelo, Erin T; Mehrara, Babak; Heller, Glenn; Münz, Christian; Altan-Bonnet, Gregoire; Young, James W

    2012-05-31

    Human CD34(+) progenitor-derived Langerhans-type dendritic cells (LCs) are more potent stimulators of T-cell immunity against tumor and viral antigens in vitro than are monocyte-derived DCs (moDCs). The exact mechanisms have remained elusive until now, however. LCs synthesize the highest amounts of IL-15R-α mRNA and protein, which binds IL-15 for presentation to responder lymphocytes, thereby signaling the phosphorylation of signal transducer and activator of transcription 5 (pSTAT5). LCs electroporated with Wilms tumor 1 (WT1) mRNA achieve sufficiently sustained presentation of antigenic peptides, which together with IL-15R-α/IL-15, break tolerance against WT1 by stimulating robust autologous, WT1-specific cytolytic T-lymphocytes (CTLs). These CTLs develop from healthy persons after only 7 days' stimulation without exogenous cytokines and lyse MHC-restricted tumor targets, which include primary WT1(+) leukemic blasts. In contrast, moDCs require exogenous rhuIL-15 to phosphorylate STAT5 and attain stimulatory capacity comparable to LCs. LCs therefore provide a more potent costimulatory cytokine milieu for T-cell activation than do moDCs, thus accounting for their superior stimulation of MHC-restricted Ag-specific CTLs without need for exogenous cytokines. These data support the use of mRNA-electroporated LCs, or moDCs supplemented with exogenous rhuIL-15, as vaccines for cancer immunotherapy to break tolerance against self-differentiation antigens shared by tumors.

  3. Study of serum soluble vascular cell adhesion molecule-1 levels in type 2 diabetic patients with diabetic retinopathy

    International Nuclear Information System (INIS)

    Li Fangdu; Chu Qiaomei

    2002-01-01

    To study the change and the correlation of serum soluble vascular cell adhesion molecule-1 (sV-CAM-1) levels with diabetic retinopathy in type 2 diabetic patients, serum sVCAM-1 levels were measured in duplicate by ELISA in 85 type 2 diabetic patients; fundus examination was performed by an ophthalmologist using ophthalmoscope or fundus fluorescein angiography, and the findings were graded as: no signs of diabetic retinopathy (NDR), background diabetic retinopathy (BDR) and proliferative diabetic retinopathy (PDR). Serum sVCAM-1 levels were significantly higher in the PDR and BDR groups than those in the control and NDR groups respectively (P<0.01). NDR group showed significantly increased serum sVCAM-levels compared with control group (P<0.01). In contrast, serum sVCAM-1 levels were not related to the presence of blood glucose, serum insulin levels or known diabetic duration. Authors' results suggest that serum sVCAM-1 might be implicated in the development of the diabetic retinopathy, and could assess the severity of diabetic retinopathy. The measurement of serum sVCAM-1 levels in 2 type diabetic patients may be clinically useful for early diagnosis or treatment of diabetic retinopathy

  4. Interleukin (IL)-23 mediates Toxoplasma gondii-induced immunopathology in the gut via matrixmetalloproteinase-2 and IL-22 but independent of IL-17

    DEFF Research Database (Denmark)

    Muñoz, Melba; Heimesaat, Markus M; Danker, Kerstin

    2009-01-01

    Peroral infection with Toxoplasma gondii leads to the development of small intestinal inflammation dependent on Th1 cytokines. The role of Th17 cells in ileitis is unknown. We report interleukin (IL)-23-mediated gelatinase A (matrixmetalloproteinase [MMP]-2) up-regulation in the ileum of infected...... mice. MMP-2 deficiency as well as therapeutic or prophylactic selective gelatinase blockage protected mice from the development of T. gondii-induced immunopathology. Moreover, IL-23-dependent up-regulation of IL-22 was essential for the development of ileitis, whereas IL-17 was down...

  5. Clinical significance of measurements of serum IL-6 levels in patients with cardiovascular and cerebrovascular diseases

    International Nuclear Information System (INIS)

    Wu Cuihua; Luo Nanping; Zhang Daojie; Wei Hong

    2004-01-01

    Objective: To explore the clinical significance of changes of serum IL-6 levels in patients with cardiovascular and cerebrovascular diseases. Methods: Serum IL-6 levels were determined with RIA in 35 patients with coronary heart disease, 20 patients with essential hypertension, 28 patients with cerebral infarction and 30 controls. Results: Serum IL-6 levels in patients with coronary heart disease and cerebral infarction were significantly higher than those in the controls (P 0.05). Conclusion: Serum IL-6 levels changes could reflect the severity of the inflammatory process and would be helpful in clinical assessment. (authors)

  6. Baseline serum CXCL10 and IL-12 levels may predict severe asthmatics' responsiveness to omalizumab.

    Science.gov (United States)

    Suzukawa, Maho; Matsumoto, Hisako; Ohshima, Nobuharu; Tashimo, Hiroyuki; Asari, Isao; Tajiri, Tomoko; Niimi, Akio; Nagase, Hiroyuki; Matsui, Hirotoshi; Kobayashi, Nobuyuki; Shoji, Shunsuke; Ohta, Ken

    2018-01-01

    Omalizumab, a humanized anti-IgE monoclonal antibody, is the first molecularly targeted drug for severe asthmatics. However, responses to omalizumab vary widely among patients. This study aimed to assess the potential of baseline serum cytokine levels as predictors of responsiveness to omalizumab. Thirty-one patients with severe, persistent asthma were enrolled in this study and administered omalizumab for at least 1 year. Response to omalizumab was assessed based on the physician's global evaluation of treatment effectiveness (GETE) at 48 weeks of treatment. Blood samples were collected at baseline and 16 and 32 weeks after starting omalizumab and measured for 30 cytokines by Luminex 200 and ELISA. Exhaled nitric oxide (FeNO) levels, peripheral blood eosinophil counts, pre-bronchodilator pulmonary functions and Asthma Quality of Life Questionnaire scores were determined at baseline and 16, 32 and 48 weeks after starting omalizumab. The numbers of clinically significant asthma exacerbations in the previous year and during 48 weeks of treatment with omalizumab were assessed. GETE assessment showed 19 responders (61.3%) and 12 non-responders (38.7%). Responders showed significantly higher levels of CXCL10 and IL-12 at baseline compared to non-responders (CXCL10: responders, 1530.0 ± 315.2 pg/ml vs. non-responders, 1066.0 ± 396.8 pg/ml, P = 0.001; IL-12: responders, 60.2 ± 39.2 pg/ml vs. non-responders, 32.2 ± 26.3 pg/ml, P = 0.04). ROC curves to distinguish responders from non-responders using the baseline serum CXCL10 level showed a good AUC of 0.83. At 32 weeks of omalizumab therapy, serum CXCL10 tended to be increased (1350 ± 412.3 pg/ml at baseline vs. 1529 ± 637.6 pg/ml at 32 weeks, P = 0.16) and serum IL-12 tended to be decreased (49.4 ± 37.0 pg/ml at baseline vs. 43.9 ± 30.9 pg/ml at 32 weeks, P = 0.05). On the other hand, serum IL-5 and PDGF were significantly decreased (IL-5: 54.2 ± 13.8 pg/ml at baseline vs. 49

  7. Muscle glycogen depletion following 75-km of cycling is not linked to increased muscle IL-6, IL-8, and MCP-1 mRNA expression and protein content

    Directory of Open Access Journals (Sweden)

    David Christopher Nieman

    2016-09-01

    Full Text Available The cytokine response to heavy exertion varies widely for unknown reasons, and this study evaluated the relative importance of glycogen depletion, muscle damage, and stress hormone changes on blood and muscle cytokine measures. Cyclists (N=20 participated in a 75-km cycling time trial (168±26.0 min, with blood and vastus lateralis muscle samples collected before and after. Muscle glycogen decreased 77.2±17.4%, muscle IL-6, IL-8, and MCP-1 mRNA increased 18.5±2.8-, 45.3±7.8-, and 8.25±1.75-fold, and muscle IL-6, IL-8, and MCP-1 protein increased 70.5±14.1%, 347±68.1%, and 148±21.3%, respectively (all, P<0.001. Serum myoglobin and cortisol increased 32.1±3.3 to 242±48.3 mg/mL, and 295±27.6 to 784±63.5 nmol/L, respectively (both P<0.001. Plasma IL-6, IL-8, and MCP-1 increased 0.42±0.07 to 18.5±3.8, 4.07±0.37 to 17.0±1.8, and 96.5±3.7 to 240±21.6 pg/mL, respectively (all P<0.001. Increases in muscle IL-6, IL-8, and MCP-1 mRNA were unrelated to any of the outcome measures. Muscle glycogen depletion was related to change in plasma IL-6 (r=0.462, P=0.040, with change in myoglobin related to plasma IL-8 (r=0.582, P=0.007 and plasma MCP-1 (r=0.457, P=0.043, and muscle MCP-1 protein (r=0.588, P=0.017; cortisol was related to plasma IL-8 (r=0.613, P=0.004, muscle IL-8 protein (r=0.681, P=0.004, and plasma MCP-1 (r=0.442, P=0.050. In summary, this study showed that muscle IL-6, IL-8, and MCP-1 mRNA expression after 75-km cycling was unrelated to glycogen depletion and muscle damage, with change in muscle glycogen related to plasma IL-6, and changes in serum myoglobin and cortisol related to the chemotactic cytokines IL-8 and MCP-1.

  8. IL2RA/CD25 Gene Polymorphisms: Uneven Association with Multiple Sclerosis (MS) and Type 1 Diabetes (T1D)

    Science.gov (United States)

    Alcina, Antonio; Fedetz, María; Ndagire, Dorothy; Fernández, Oscar; Leyva, Laura; Guerrero, Miguel; Abad-Grau, María M.; Arnal, Carmen; Delgado, Concepción; Lucas, Miguel; Izquierdo, Guillermo; Matesanz, Fuencisla

    2009-01-01

    Background IL-2 receptor (IL2R) alpha is the specific component of the high affinity IL2R system involved in the immune response and in the control of autoimmunity. Methods and Results Here we perform a replication and fine mapping of the IL2RA gene region analyzing 3 SNPs previously associated with multiple sclerosis (MS) and 5 SNPs associated with type 1 diabetes (T1D) in a collection of 798 MS patients and 927 matched Caucasian controls from the south of Spain. We observed association with MS in 6 of 8 SNPs. The rs1570538, at the 3′- UTR extreme of the gene, previously reported to have a weak association with MS, is replicated here (P = 0.032). The most associated T1D SNP (rs41295061) was not associated with MS in the present study. However, the rs35285258, belonging to another independent group of SNPs associated with T1D, showed the maximal association in this study but different risk allele. We replicated the association of only one (rs2104286) of the two IL2RA SNPs identified in the recently performed genome-wide association study of MS. Conclusions These findings confirm and extend the association of this gene with MS and reveal a genetic heterogeneity of the associated polymorphisms and risk alleles between MS and T1D suggesting different immunopathological roles of IL2RA in these two diseases. PMID:19125193

  9. Impact of IL1B gene polymorphisms and interleukin 1B levels on susceptibility to spontaneous preterm birth.

    Science.gov (United States)

    Langmia, Immaculate M; Apalasamy, Yamunah D; Omar, Siti Z; Mohamed, Zahurin

    2016-11-01

    Genetic factors influence susceptibility to preterm birth (PTB) and the immune pathway of PTB that involves the production of cytokines such as interleukins has been implicated in PTB disease. The aim of this study is to investigate the association of interleukin 1β (IL1B) gene polymorphisms and IL1B levels with spontaneous PTB. Peripheral maternal blood from 495 women was used for extraction of DNA and genotyping was carried out using the Sequenom MassARRAY platform. Maternal plasma was used to measure IL1B levels. There was no significant association between the allelic and genotype distribution of IL1B single nucleotide polymorphism (SNP) (rs1143634, rs1143627, rs16944) and the risk of PTB among Malaysian Malay women (rs1143634, P=0.722; rs1143627, P=0.543; rs16944, P=0.615). However, IL1B levels were significantly different between women who delivered preterm compared with those who delivered at term (P=0.030); high mean levels were observed among Malay women who delivered at preterm (mean=32.52) compared with term (mean=21.68). IL1B SNPs were not associated with IL1B plasma levels. This study indicates a significant association between IL1B levels and reduced risk of PTB among the Malaysian Malay women. This study shows the impact of IL1B levels on susceptibility to PTB disease; however, the high levels of IL1B observed among women in the preterm group are not associated with IL1B SNPs investigated in this study; IL1B high levels may be because of other factors not explored in this study and therefore warrant further investigation.

  10. Mast cells limit extracellular levels of IL-13 via a serglycin proteoglycan-serine protease axis.

    Science.gov (United States)

    Waern, Ida; Karlsson, Iulia; Thorpe, Michael; Schlenner, Susan M; Feyerabend, Thorsten B; Rodewald, Hans-Reimer; Åbrink, Magnus; Hellman, Lars; Pejler, Gunnar; Wernersson, Sara

    2012-12-01

    Mast cell (MC) granules contain large amounts of proteases of the chymase, tryptase and carboxypeptidase A (MC-CPA) type that are stored in complex with serglycin,a proteoglycan with heparin side chains. Hence, serglycinprotease complexes are released upon MC degranulation and may influence local inflammation. Here we explored the possibility that a serglycin-protease axis may regulate levels of IL-13, a cytokine involved in allergic asthma. Indeed, we found that wild-type MCs efficiently degraded exogenous or endogenously produced IL-13 upon degranulation,whereas serglycin −/− MCs completely lacked this ability.Moreover, MC-mediated IL-13 degradation was blocked both by a serine protease inhibitor and by a heparin antagonist,which suggests that IL-13 degradation is catalyzed by serglycin-dependent serine proteases and that optimal IL-13 degradation is dependent on both the serglycin and the protease component of the serglycin-protease complex.Moreover, IL-13 degradation was abrogated in MC-CPA −/−MC cultures, but was normal in cultures of MCs with an inactivating mutation of MC-CPA, which suggests that the IL-13-degrading serine proteases rely on MC-CPA protein.Together, our data implicate a serglycin-serine protease axis in the regulation of extracellular levels of IL-13. Reduction of IL-13 levels through this mechanism possibly can provide a protective function in the context of allergic inflammation.

  11. Selective Inhibitors of Kv11.1 Regulate IL-6 Expression by Macrophages in Response to TLR/IL-1R Ligands

    Directory of Open Access Journals (Sweden)

    Cheryl Hunter

    2010-01-01

    Full Text Available The mechanism by which the platelet-endothelial cell adhesion molecule PECAM-1 regulates leukodiapedesis, vascular endothelial integrity, and proinflammatory cytokine expression in vivo is not known. We recently identified PECAM-1 as a negative regulator of Kv11.1, a specific voltage-gated potassium channel that functioned in human macrophages to reset a resting membrane potential following depolarization. We demonstrate here that dofetilide (DOF, a selective inhibitor of the Kv11.1 current, had a profound inhibitory effect on neutrophil recruitment in mice following TLR/IL-1R–elicited peritonitis or intrascrotal injection of IL-1β, but had no effect on responses seen with TNFα. Furthermore, inhibitors of Kv11.1 (DOF, E4031, and astemizole, but not Kv1.3 (margatoxin, suppressed the expression of IL-6 and MCP-1 cytokines by murine resident peritoneal macrophages, while again having no effect on TNFα. In contrast, IL-6 expression by peritoneal mesothelial cells was unaffected. Using murine P388 cells, which lack endogenous C/EBPβexpression and are unresponsive to LPS for the expression of both IL-6 and MCP-1, we observed that DOF inhibited LPS-induced expression of IL-6 mRNA following ectopic expression of wild-type C/EBPβ, but not a serine-64 point mutant. Finally, DOF inhibited the constitutive activation of cdk2 in murine peritoneal macrophages; cdk2 is known to phosphorylate C/EBPβ at serine-64. Taken together, our results implicate a potential role for Kv11.1 in regulating cdk2 and C/EBPβ activity, where robust transactivation of both IL-6 and MCP-1 transcription is known to be dependent on serine-64 of C/EBPβ. Our data might also explain the altered phenotypes displayed by PECAM-1 knockout mice in several disease models.

  12. Genetic ablation of soluble tumor necrosis factor with preservation of membrane tumor necrosis factor is associated with neuroprotection after focal cerebral ischemia

    DEFF Research Database (Denmark)

    Madsen, Pernille M; Clausen, Bettina H; Degn, Matilda

    2016-01-01

    Microglia respond to focal cerebral ischemia by increasing their production of the neuromodulatory cytokine tumor necrosis factor, which exists both as membrane-anchored tumor necrosis factor and as cleaved soluble tumor necrosis factor forms. We previously demonstrated that tumor necrosis factor...... reduced infarct volumes at one and five days after stroke. This was associated with improved functional outcome after experimental stroke. No changes were found in the mRNA levels of tumor necrosis factor and tumor necrosis factor-related genes (TNFR1, TNFR2, TACE), pro-inflammatory cytokines (IL-1β, IL-6...... knockout mice display increased lesion volume after focal cerebral ischemia, suggesting that tumor necrosis factor is neuroprotective in experimental stroke. Here, we extend our studies to show that mice with intact membrane-anchored tumor necrosis factor, but no soluble tumor necrosis factor, display...

  13. Leptin, soluble leptin receptor, and free leptin index in patients with metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Elena N. Smirnova

    2017-06-01

    Full Text Available Aim. To assess the levels of leptin, its soluble receptor, and index of the formation of free leptin in metabolic syndrome (MS. Materials and methods. The study included 110 individuals with obesity and overweight. The group 1 consisted of 70 patients with MS (IDF, 2005, the average body mass index (BMI 38.4 ± 4.4 kg/m2, aged 48.2 ± 2.4 years, with arterial hypertension (AH 1–2 degree, without regular antihypertensive therapy. Group 2 – "healthy" obesity accounted for 40 patients aged 38.4 ± 6.2 years, BMI 36.0 ± 5.5 kg/m2 without hypertension and metabolic disorders. Group 3 consisted of 30 healthy persons, BMI 27.1 ± 1.3 kg/m2. All patients were evaluated for insulin, HOMA index, leptin, leptin receptor, leptin free index (calculated as the ratio of leptin (ng/ml to the leptin receptor (ng/ml, multiplied by 100. Results: In patients with MS as compared to other two groups there were higher levels of HOMA IR index, leptin and free leptin index. Values of leptin receptor in groups 1 and 2 did not differ significantly and were lower than in healthy persons. The free leptin index was significantly higher in MS group relative to the group 2 and 15 times higher than in the healthy individuals. Free leptin index correlated with values of BMI (R = 0.32; p = 0.02, blood pressure (R = 0.3; p = 0.04, uric acid (R = 0.27; p = 0.04, triglycerides (R = 0.42; p = 0.02, index HOMA-IR (R = 0.45; p = 0.02. Conclusions: Reduction of soluble leptin receptor, depending on the degree of abdominal obesity, may cause progression of leptin resistance in patients with MS. The levels of leptin and soluble leptin receptor appears to have dramatical gender differences. Calculation of free leptin index should be used for the objective evaluation of leptin resistance, regardless of gender, degree of obesity, and other metabolic parameters.

  14. Urinary Levels of IL-1β and GDNF in Preterm Neonates as Potential Biomarkers of Motor Development: A Prospective Study

    Directory of Open Access Journals (Sweden)

    Rafael Coelho Magalhães

    2017-01-01

    Full Text Available Objectives. To evaluate the association between inflammatory biomarkers, neurotrophic factors, birth conditions, and the presence of motor development abnormalities in preterm neonates. Methods. Plasma and urinary levels of cytokines (IL-1β, IL-6, IL-10, TNF, and IL-12p70, chemokines (CXCL8/IL-8, CCL2/MCP-1, CCL5/RANTES, CXCL10/IP-10, and CXCL9/MIG, and neurotrophic factors (BDNF and GDNF were evaluated in 40 preterm neonates born between 28 and 32 incomplete weeks of gestation, at four distinct time points: at birth (umbilical cord blood (T0, at 48 (T1, at 72 hours (T2, and at 3 weeks after birth (T3. Biomarkers levels were compared between different time points and then associated with Test of Infant Motor Performance (TIMP percentiles. Results. Maternal age, plasma, and urinary concentrations of inflammatory molecules and neurotrophic factors were significantly different between groups with normal versus lower than expected motor development. Higher levels of GDNF were found in the group with lower than expected motor development, while IL-1β and CXCL8/IL-8 values were higher in the group with typical motor development. Conclusion. Measurements of cytokines and neurotrophic factors in spot urine may be useful in the follow-up of motor development in preterm neonates.

  15. The correlation of adiponectin, IL-6 with insulin resistance and macrovascular lesion in type 2 diabetes

    International Nuclear Information System (INIS)

    Shi Bimin; Cheng Xingbo

    2006-01-01

    Objective: To investigate the serum level changes of adiponectin and IL-6 and their relation with macrovascular complications in patients with type 2 diabetes before and after thiazolidinediones intervention. Methods: Serum adiponectin and IL-6 level were examined using ELISA method in 16 patients with obese type 2 diabetes, 24 patients with diabetes with normal body weight, and 14 controls. Their body mass index (BMI) and HOMA-IR were calculated and the internal membrane thickness (IMT) of carotid artery was also observed. These indexes were reexamined after thiazolidinediones (Avandia) intervention and correlation analysis was performed. Results: A decreased serum concentration of adiponectin and an elevated level of IL-6 and HOMA-IR were found in diabetes group especially in those with obesity (P<0.01). Serum adiponectin was negatively correlated with HOMA-IR, BMI, IL-6 and IMT while IL-6 was positively correlated with the above-mentioned indexes. After treatment with thiazolidinediones, the insulin resistance state and adponectin and IL-6 were significantly improved especially in those with obesity (P<0.05, P<0.01). Conclusion: Adiponectin is closed correlated with obesity (P<0.05, P<0.01). Conclusion: Adiponectin is closed correlated with obesity, insulin resistance and macrovascular lesions. IL-6 may be involved in the mechanism of insulin resistance in type 2 diabetes patients especially in the obese diabetes group. In addition to enhance the sensitivity of insulin, thiazolidinediones may play a potential role in anti-inflammation, anti-atherosclerosis and immuno-regulation. (authors)

  16. Neonatal immune responses to TLR2 stimulation: Influence of maternal atopy on Foxp3 and IL-10 expression

    Directory of Open Access Journals (Sweden)

    Gold Diane R

    2006-03-01

    Full Text Available Abstract Background Maternal atopic background and stimulation of the adaptive immune system with allergen interact in the development of allergic disease. Stimulation of the innate immune system through microbial exposure, such as activation of the innate Toll-like-receptor 2 (TLR2, may reduce the development of allergy in childhood. However, little is known about the immunological effects of microbial stimulation on early immune responses and in association with maternal atopy. Methods We analyzed immune responses of cord blood mononuclear cells (CBMC from 50 healthy neonates (31 non-atopic and 19 atopic mothers. Cells were stimulated with the TLR2 agonist peptidoglycan (Ppg or the allergen house dust mite Dermatophagoides farinae (Derf1, and results compared to unstimulated cells. We analyzed lymphocyte proliferation and cytokine secretion of CBMC. In addition, we assessed gene expression associated with T regulatory cells including the transcription factor Foxp3, the glucocorticoid-induced TNF receptor (GITR, and the cytotoxic lymphocyte antigen 4 (CTLA4. Lymphocyte proliferation was measured by 3H-Thymidine uptake, cytokine concentrations determined by ELISA, mRNA expression of T cell markers by real-time RT-PCR. Results Ppg stimulation induced primarily IL-10 cytokine production, in addition to IFN-γ, IL-13 and TNF-α secretion. GITR was increased following Ppg stimulation (p = 0.07. Ppg-induced IL-10 production and induction of Foxp3 were higher in CBMC without, than with maternal atopy (p = 0.04, p = 0.049. IL-10 production was highly correlated with increased expression of Foxp3 (r = 0.53, p = 0.001, GITR (r = 0.47, p = 0.004 and CTLA4 (r = 0.49, p = 0.003, independent of maternal atopy. Conclusion TLR2 stimulation with Ppg induces IL-10 and genes associated with T regulatory cells, influenced by maternal atopy. Increased IL-10 and Foxp3 induction in CBMC of non-atopic compared to atopic mothers, may indicate an increased capacity to

  17. IL-1 signal affects both protection and pathogenesis of virus-induced chronic CNS demyelinating disease

    Directory of Open Access Journals (Sweden)

    Kim Byung S

    2012-09-01

    Full Text Available Abstract Background Theiler’s virus infection induces chronic demyelinating disease in mice and has been investigated as an infectious model for multiple sclerosis (MS. IL-1 plays an important role in the pathogenesis of both the autoimmune disease model (EAE and this viral model for MS. However, IL-1 is known to play an important protective role against certain viral infections. Therefore, it is unclear whether IL-1-mediated signaling plays a protective or pathogenic role in the development of TMEV-induced demyelinating disease. Methods Female C57BL/6 mice and B6.129S7-Il1r1tm1Imx/J mice (IL-1R KO were infected with Theiler’s murine encephalomyelitis virus (1 x 106 PFU. Differences in the development of demyelinating disease and changes in the histopathology were compared. Viral persistence, cytokine production, and immune responses in the CNS of infected mice were analyzed using quantitative PCR, ELISA, and flow cytometry. Results Administration of IL-1β, thereby rending resistant B6 mice susceptible to TMEV-induced demyelinating disease, induced a high level of Th17 response. Interestingly, infection of TMEV into IL-1R-deficient resistant C57BL/6 (B6 mice also induced TMEV-induced demyelinating disease. High viral persistence was found in the late stage of viral infection in IL-1R-deficient mice, although there were few differences in the initial anti-viral immune responses and viral persistent levels between the WT B6 and IL-1R-deficiecent mice. The initial type I IFN responses and the expression of PDL-1 and Tim-3 were higher in the CNS of TMEV-infected IL-1R-deficient mice, leading to deficiencies in T cell function that permit viral persistence. Conclusions These results suggest that the presence of high IL-1 level exerts the pathogenic role by elevating pathogenic Th17 responses, whereas the lack of IL-1 signals promotes viral persistence in the spinal cord due to insufficient T cell activation by elevating the production of

  18. Proinflammatory Cytokine IL-6 and JAK-STAT Signaling Pathway in Myeloproliferative Neoplasms

    Directory of Open Access Journals (Sweden)

    Vladan P. Čokić

    2015-01-01

    Full Text Available The recent JAK1/2 inhibitor trial in myeloproliferative neoplasms (MPNs showed that reducing inflammation can be more beneficial than targeting gene mutants. We evaluated the proinflammatory IL-6 cytokine and JAK-STAT signaling pathway related genes in circulating CD34+ cells of MPNs. Regarding laboratory data, leukocytosis has been observed in polycythemia vera (PV and JAK2V617F mutation positive versus negative primary myelofibrosis (PMF patients. Moreover, thrombocytosis was reduced by JAK2V617F allele burden in essential thrombocythemia (ET and PMF. 261 significantly changed genes have been detected in PV, 82 in ET, and 94 genes in PMF. The following JAK-STAT signaling pathway related genes had augmented expression in CD34+ cells of MPNs: CCND3 and IL23A regardless of JAK2V617F allele burden; CSF3R, IL6ST, and STAT1/2 in ET and PV with JAK2V617F mutation; and AKT2, IFNGR2, PIM1, PTPN11, and STAT3 only in PV. STAT5A gene expression was generally reduced in MPNs. IL-6 cytokine levels were increased in plasma, as well as IL-6 protein levels in bone marrow stroma of MPNs, dependent on JAK2V617F mutation presence in ET and PMF patients. Therefore, the JAK2V617F mutant allele burden participated in inflammation biomarkers induction and related signaling pathways activation in MPNs.

  19. Dietary fiber content influences soluble carbohydrate levels in ruminal fluids.

    Science.gov (United States)

    Pinder, R S; Patterson, J A; O'Bryan, C A; Crandall, P G; Ricke, S C

    2012-01-01

    The soluble carbohydrate concentration of ruminal fluid, as affected by dietary forage content (DFC) and/or ruminally undegradable intake protein content (UIPC), was determined. Four ruminally cannulated steers, in a 4 × 4 Latin square design, were offered diets containing high (75 % of DM) or low (25 % of DM) DFC and high (6 % of DM) or low (5 % of DM) UIPC, in a 2 × 2 factorial arrangement. Zinc-treated SBM was the primary UIP source. Soluble hexose concentration (145.1 μM) in ruminal fluid (RF) of steers fed low DFC diets exhibited a higher trend (P = 0.08) than that (124.5 μM) of steers fed high DFC diets. UIPC did not modulate (P = 0.54) ruminal soluble hexose concentrations. Regardless of diet, soluble hexose concentration declined immediately after feeding and did not rise until 3 h after feeding (P ruminal fluid could not be determined. However, unsubstituted xylose and arabinose were excluded. These data indicate that: (i) soluble carbohydrate concentrations remain in ruminal fluid during digestion and fermentation; (ii) slight diurnal changes began after feeding; (iii) DFC influences the soluble carbohydrate concentration in RF; and (iv) UIPC of these diets does not affect the soluble carbohydrate concentration of RF.

  20. Solubility of rare earth-iron borates in the Bi2O3-B2O3 melt and their crystallization

    International Nuclear Information System (INIS)

    Al'shinskaya, L.I.; Leonyuk, N.I.; Nadezhnaya, T.B.; Timchenko, T.I.

    1979-01-01

    The temperature dependence of solubility of RFe 3 (BO 3 ) 4 (R=Y, Gd, Nd, Er) double borates in the Bi 2 O 3 -B 2 O 3 solution-melt is studied. The solubility curves in the range from 25 to 52 mol% are plotted. The character of curves is almost similar. At equal temperatures YFe 3 (BO 3 ) 4 and ErFe 3 (BO 3 ) 4 have the highest solubility and GaFe 3 (BO 3 ) 4 - the lowest one. It is shown that in the Bi 2 O 3 -B 2 O 3 base solution-melt the wide temperature range of monophase crystallization of rare earth - iron borates exists and the stratification is not observed. Thus, for the first time obtained are the crystals of rare earth-iron borates suitable for the investigation of their physical properties

  1. Genetic Ablation of Soluble TNF Does Not Affect Lesion Size and Functional Recovery after Moderate Spinal Cord Injury in Mice

    Directory of Open Access Journals (Sweden)

    Ditte Gry Ellman

    2016-01-01

    Full Text Available Traumatic spinal cord injury (SCI is followed by an instant increase in expression of the microglial-derived proinflammatory cytokine tumor necrosis factor (TNF within the lesioned cord. TNF exists both as membrane-anchored TNF (mTNF and as cleaved soluble TNF (solTNF. We previously demonstrated that epidural administration of a dominant-negative inhibitor of solTNF, XPro1595, to the contused spinal cord resulted in changes in Iba1 protein expression in microglia/macrophages, decreased lesion volume, and improved locomotor function. Here, we extend our studies using mice expressing mTNF, but no solTNF (mTNFΔ/Δ, to study the effect of genetic ablation of solTNF on SCI. We demonstrate that TNF levels were significantly decreased within the lesioned spinal cord 3 days after SCI in mTNFΔ/Δ mice compared to littermates. This decrease did, however, not translate into significant changes in other pro- and anti-inflammatory cytokines (IL-10, IL-1β, IL-6, IL-5, IL-2, CXCL1, CCL2, or CCL5, despite a tendency towards increased IL-10 and decreased IL-1β, TNFR1, and TNFR2 levels in mTNFΔ/Δ mice. In addition, microglial and leukocyte infiltration, activation state (Iba1, CD11b, CD11c, CD45, and MHCII, lesion size, and functional outcome after moderate SCI were comparable between genotypes. Collectively, our data demonstrate that genetic ablation of solTNF does not significantly modulate postlesion outcome after SCI.

  2. Protease activity of Per a 10 potentiates Th2 polarization by increasing IL-23 and OX40L.

    Science.gov (United States)

    Agrawal, Komal; Kale, Sagar L; Arora, Naveen

    2015-12-01

    Proteases are implicated in exacerbation of allergic diseases. In this study, the role of proteolytic activity of Per a 10 was evaluated on Th2 polarization. Intranasal administration of Per a 10 in mice led to allergic airway inflammation as seen by higher IgE levels, cellular infiltration, IL-17A, and Th2 cytokines, whereas, inactive (Δ)Per a 10 showed attenuated response. There was an increased OX40L expression on lung and lymph node dendritic cells in Per a 10 immunized group and on Per a 10 stimulated BMDCs. Reduction in CD40 expression without any change at transcript level in lungs of Per a 10 immunized mice suggested CD40 cleavage. BMDCs pulsed with Per a 10 showed reduced CD40 expression with lower IL-12p70 secretion as compared to heat inactivated Per a 10. IL-23, TNF-α, and IL-6 levels were significantly higher in Per a 10 stimulated BMDCs supernatant. In DC-T cell coculture studies, Per a 10 pulsed BMDCs showed higher levels of IL-4 and IL-13 that were reduced on blocking of either IL-23 or OX40L. In conclusion, the data suggests a critical role of protease activity of Per a 10 in promoting Th2 polarization by increasing IL-23 secretion and OX40L expression on dendritic cells. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Production of bioactive soluble interleukin-15 in complex with interleukin-15 receptor alpha from a conditionally-replicating oncolytic HSV-1.

    Directory of Open Access Journals (Sweden)

    David C Gaston

    Full Text Available Oncolytic type-1 herpes simplex viruses (oHSVs lacking the γ134.5 neurovirulence gene are being evaluated for treatment of a variety of malignancies. oHSVs replicate within and directly kill permissive cancer cells. To augment their anti-tumor activity, oHSVs have been engineered to express immunostimulatory molecules, including cytokines, to elicit tumor-specific immune responses. Interleukin-15 (IL-15 holds potential as an immunotherapeutic cytokine because it has been demonstrated to promote both natural killer (NK cell-mediated and CD8(+ T cell-mediated cytotoxicity against cancer cells. The purpose of these studies was to engineer an oHSV producing bioactive IL-15. Two oHSVs were constructed encoding murine (mIL-15 alone (J100 or with the mIL-15 receptor α (mIL-15Rα, J100D to determine whether co-expression of these proteins is required for production of bioactive mIL-15 from oHSV. The following were demonstrated: i both oHSVs retain replication competence and cytotoxicity in permissive tumor cell lines. ii Enhanced production of mIL-15 was detected in cell lysates of neuro-2a cells following J100D infection as compared to J100 infection, suggesting that mIL-15Rα improved mIL-15 production. iii Soluble mIL-15 in complex with mIL-15Rα was detected in supernates from J100D-infected, but not J100-infected, neuro-2a, GL261, and CT-2A cells. These cell lines vary in permissiveness to oHSV replication and cytotoxicity, demonstrating soluble mIL-15/IL-15Rα complex production from J100D was independent of direct oHSV effects. iv The soluble mIL-15/IL-15Rα complex produced by J100D was bioactive, stimulating NK cells to proliferate and reduce the viability of syngeneic GL261 and CT-2A cells. v J100 and J100D were aneurovirulent inasmuch as no neuropathologic effects were documented following direct inoculation into brains of CBA/J mice at up to 1x10(7 plaque forming units. The production of mIL-15/mIL-15Rα from multiple tumor lines, as well

  4. Circulating levels of TNF-alpha and IL-6-relation to truncal fat mass and muscle mass in healthy elderly individuals and in patients with type-2 diabetes

    DEFF Research Database (Denmark)

    Pedersen, Maria; Bruunsgaard, Helle; Weis, Nina

    2003-01-01

    The purpose of the current study was to test the hypothesis that an altered fat distribution in elderly healthy subjects and in patients with type-2 diabetes contributes to high circulating levels of interleukin (IL)-6 and tumor necrotic factor (TNF)-alpha, which secondly is related to lower muscle...... mass. Twenty young controls, (20-35 yr), 20 healthy elderly subjects (65-80 yr) and 16 elderly patients with type 2 diabetes (65-80 yr) were included in a cross sectional study. Plasma levels of TNF-alpha and IL-6 were measured after an overnight fast. Dual-energy X-ray absorptiometry and total body...... potassium counting measured truncal fat, appendicular skeletal muscle mass (ASM) and body cell mass (BCM), respectively. TNF-alpha, IL-6 and the relative truncal fat mass were higher in elderly compared with young controls. ASM was lower in diabetic men than in young controls and BCM was lower in elderly...

  5. The role of genetic variation across IL-1β, IL-2, IL-6, and BDNF in antipsychotic-induced weight gain.

    Science.gov (United States)

    Fonseka, Trehani M; Tiwari, Arun K; Gonçalves, Vanessa F; Lieberman, Jeffrey A; Meltzer, Herbert Y; Goldstein, Benjamin I; Kennedy, James L; Kennedy, Sidney H; Müller, Daniel J

    2015-01-01

    Antipsychotics with high weight gain-inducing propensities influence the expression of immune and neurotrophin genes, which have been independently related to obesity indices. Thus, we investigated whether variants in the genes encoding interleukin (IL)-1β, IL-2, and IL-6 and brain-derived neurotrophic factor (BDNF) Val66Met are associated with antipsychotic-induced weight gain (AIWG). Nineteen polymorphisms were genotyped using Taqman(®) assays in 188 schizophrenia patients on antipsychotic treatment for up to 14 weeks. Mean weight change (%) from baseline was compared across genotypic groups using analysis of covariance (ANCOVA). Epistatic effects between cytokine polymorphisms and BDNF Val66Met were tested using Model-Based Multifactor Dimensionality Reduction. In European patients, IL-1β rs16944*GA (P = 0.013, Pcorrected = 0.182), IL-1β rs1143634*G (P = 0.001, Pcorrected = 0.014), and BDNF Val66Met (Val/Val, P = 0.004, Pcorrected = 0.056) were associated with greater AIWG, as were IL-1β rs4849127*A (P = 0.049, Pcorrected = 0.784), and IL-1β rs16944*GA (P = 0.012, Pcorrected = 0.192) in African Americans. BDNF Val66Met interacted with both IL-1β rs13032029 (Val/Met+ TT, PPerm = 0.029), and IL-6 rs2069837 (Val/Val+ AA, PPerm = 0.021) in Europeans, in addition to IL-1β rs16944 (Val/Val+ GA, PPerm = 0.006) in African Americans. SNPs across IL-1β and BDNF Val66Met may influence AIWG. Replication of these findings in larger, independent samples is warranted.

  6. Annexin A2 and its downstream IL-6 and HB-EGF as secretory biomarkers in the differential diagnosis of Her-2 negative breast cancer.

    Science.gov (United States)

    Shetty, Praveenkumar; Patil, Vidya S; Mohan, Rajashekar; D'souza, Leonard Clinton; Bargale, Anil; Patil, Basavaraj R; Dinesh, U S; Haridas, Vikram; Kulkarni, Shrirang P

    2017-07-01

    Background AnnexinA2 (AnxA2) membrane deposition has a critical role in HB-EGF shedding as well as IL-6 secretion in breast cancer cells. This autocrine cycle has a major role in cancer cell proliferation, migration and metastasis. The objective of the study is to demonstrate annexinA2-mediated autocrine regulation via HB-EGF and IL-6 in Her-2 negative breast cancer progression. Methods Secretory annexinA2, HB-EGF and IL-6 were analysed in the peripheral blood sample of Her-2 negative ( n = 20) and positive breast cancer patients ( n = 16). Simultaneously, tissue expression was analysed by immunohistochemistry. The membrane deposition of these secretory ligands and their autocrine regulation was demonstrated using triple-negative breast cancer cell line model. Results Annexina2 and HB-EGF expression are inversely correlated with Her-2, whereas IL-6 expression is seen in both Her-2 negative and positive breast cancer cells. RNA interference studies and upregulation of annexinA2 proved that annexinA2 is the upstream of this autocrine pathway. Abundant soluble serum annexinA2 is secreted in Her-2 negative breast cancer (359.28 ± 63.73 ng/mL) compared with normal (286.10 ± 70.04 ng/mL, P breast cancer phenotypes as compared with normal ( P breast cancer tissues, increased secretion compared with normal cells, and their major role in the regulation of EGFR downstream signalling makes these molecules as a potential tissue and serum biomarker and an excellent therapeutic target in Her-2 negative breast cancer.

  7. Defective production of interleukin 2 in patients with Chagas' disease: purified IL-2 augments in vitro response in patients with chagasic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Luis Briceno

    1996-10-01

    Full Text Available The production of interleukin 2 (IL-2 by peripheral blood mononuclear cells, from patients with different clinical forms of Chagas disease and healthy controls, was evaluated after stimulation with Trypanosoma cruzi antigen, PPD and PHA. PHA induced higher production of IL-2 in infected patients than healthy controls. No diferences were found between infected groups. With PPD the trend was similar, the only difference was that asymptomatic infected patients (INF showed higher levels of IL-2 production than patients with cardiomyopathy (CDM. With T. cruzi antigen, most patients showed little or no IL-2 production at 24 hr, a peak at 48 hr and an abrupt fall at 72 hr. A similar pattern of IL- 2 production was observed in INF and CDM. To evaluate the physiologic relevance of the deficit in IL-2 production, we studied the effect of non-mitogenic concentratios of IL-2 in the proliferative response to specific antigens. The addition of IL-2 only enhanced the proliferative response of CDM patients. These observations suggest that patients suffering Chagas' disease, particularly CDM, have a significant reduction in the capacity to produce IL-2. These findings could be of importance in the pathogenesis of Chagas' disease.

  8. Etiological periodontal treatment with and without low-level laser therapy on IL-1β level in gingival crevicular fluid: an in vivo multicentric pilot study.

    Science.gov (United States)

    Mastrangelo, F; Dedola, A; Cattoni, F; Ferrini, F; Bova, F; Tatullo, M; Gherlone, E; Lo Muzio, L

    2018-01-01

    Cytokine proteins may have important roles during different human physiological and pathological processes. In the oral cavity, the bone loss and periodontal tissue pathology was related to inflammatory process activation. The aim of the present study was to assess the effects of etiological periodontal therapy with and without the use of Low Level Laser Therapy (LLLT) on clinical periodontal parameters and interleukin (IL)-1β level in gingival crevicular fluid (GCF) from chronic periodontitis (CP) patients. Thirty non-smoker CP patients were selected from the Foggia University Dental Clinic and other 2 private dental clinics. All patients were divided into two homogeneous randomized groups: 15 patients were treated with only scaling and root planing (group 1) and 15 patients with scaling and root planing etiological treatment and LLLT (group 2). In all sites, at baseline before treatment, the periodontal pocket depth (PPD) and bleeding on probing (BOP) were measured. In the PPD sites, the GCF samples were collected from 30 deep (≥5 mm) and shallow (≤3 mm) sites and IL-1β were evaluated at baseline, after 10 days and 1 month. In all the samples at baseline, the IL-1β concentration in GCF and BOP rate were significantly higher at deep PPD sites than at the shallow ones. After 10 days in all samples no PPD improvement was observed in the BOP rate but the IL-1 β level was statistically significantly improved (pdeep PPD sites, PPD and BOP improvements were observed. At same time, IL-1β levels were lower and statistically significantly (pdeep PPD sites with or with-out associated LLLT promotes periodontal health. Etiological treatment associated with LLLT, improves BOP and inflammation in periodontal disease. Moreover, the IL-1β concentration changes in GCF suggest these cytokines as a predictable marker of gingival inflammation in chronic periodontitis patients.

  9. Plasma cytokine IL-6 levels and subjective cognitive decline: preliminary findings.

    Science.gov (United States)

    Keegan, Andrew P; Paris, Daniel; Luis, Cheryl A; Abdullah, Laila; Ait-Ghezala, Ghania; Beaulieu-Abdelahad, David; Pryor, Makenzie; Chaykin, Jillian; Crynen, Gogce; Crawford, Fiona; Mullan, Michael

    2018-02-01

    Detection of Alzheimer's disease (AD) prior to clinical inception will be paramount for introducing disease modifying treatments. We have begun collecting baseline characteristics of a community cohort for longitudinal assessment and testing of antecedent blood-based biomarkers. We describe the baseline visit from the first 131 subjects in relationship to a commonly described cytokine, interleukin 6 (IL-6). Subjects from the community presented for a free memory screening with varying degrees of memory concern. We quantified the baseline plasma levels of the cytokine IL-6 and assessed cognition (Montreal Cognitive Assessment, MoCA) and mood (Geriatric Depression Scale, GDS) in relationship to their memory concern. Baseline MoCA scores were inversely related to age, and this association was influenced by an AD risk factor, Apolipoprotein E (APOE4) carrier status. The degree of subjective cognitive decline correlated with GDS and was inversely related to MoCA scores. Interleukin 6 levels were related to age, body mass index, and years of education. It will be important to assess how these baseline IL-6 levels and forthcoming novel biomarkers relate to future cognitive decline. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  10. Biochemical markers of bone metabolism reflect osteoclastic and osteoblastic activity in multiple myeloma

    DEFF Research Database (Denmark)

    Abildgaard, N; Glerup, H; Rungby, Jørgen

    2000-01-01

    In order to evaluate the use of recently developed assays of bone metabolism in multiple myeloma we performed a histomorphometric study of bone biopsies in 16 myeloma patients. Furthermore, we measured the levels of interleukin-6 (IL-6), soluble IL-6 receptor (IL-6sR), IL-1beta, tumour necrosis f...

  11. Association of Corynebacterium pseudotuberculosis recombinant proteins rCP09720 or rCP01850 with rPLD as immunogens in caseous lymphadenitis immunoprophylaxis.

    Science.gov (United States)

    Silva, Mara Thais de Oliveira; Bezerra, Francisco Silvestre Brilhante; de Pinho, Rodrigo Barros; Begnini, Karine Rech; Seixas, Fabiana Kommling; Collares, Tiago; Portela, Ricardo Dias; Azevedo, Vasco; Dellagostin, Odir; Borsuk, Sibele

    2018-01-02

    Caseous lymphadenitis (CLA) is a chronic disease responsible for significant economic losses in sheep and goat breeding worldwide. The treatment for this disease is not effective, and an intense vaccination schedule would be the best control strategy. In this study, we evaluated the associations of rCP09720 or rCP01850 proteins from Corynebacterium pseudotuberculosis with recombinant exotoxin phospholipase D (rPLD) as subunit vaccines in mice. Four experimental groups (10 animals each) were immunized with a sterile 0.9% saline solution (G1), rPLD (G2), rPLD + rCP09720 (G3), and rPLD + rCP01850 (G4). The mice received two doses of each vaccine at a 21-day interval and were challenged 21 days after the last immunization. The animals were evaluated daily for 40 days after the challenge, and mortality rate was recorded. The total IgG production level increased significantly in the experimental groups on day 42 after the first vaccination. Similarly, higher levels of specific IgG2a were observed in experimental groups G2, G3, and G4 compared to the IgG1 levels on day 42. G4 showed a significant (p < .05) humoral response against both antigens of the antigenic formulations. The cellular immune response induced by immunization was characterized by a significant (p < .05) production of interferon-γ compared to that in the control, while the concentrations of interleukin (IL)-4 and IL-12 were not significant in any group. A significant increase of tumor necrosis factor was observed only in G4. The survival rates after the challenge were 30% (rPLD), 40% (rPLD + rCP09720), and 50% (rPLD + rCP01850). Thus, the association of rCP01850 with rPLD resulted in the best protection against the challenge with C. pseudotuberculosis and induced a more intense type 1 T-helper cell immune response. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Interleukin 2 (IL 2) up-regulates its own receptor on a subset of human unprimed peripheral blood lymphocytes and triggers their proliferation

    International Nuclear Information System (INIS)

    Harel-Bellan, A.; Bertoglio, J.; Quillet, A.; Marchiol, C.; Wakasugi, H.; Mishall, Z.; Fradelizi, D.

    1986-01-01

    Several reports indicate that human peripheral blood lymphoctyes (PBL) seeded in culture with purified or recombinant interleukin 2 (IL 2) immediately after separation from the blood display a substantial level of proliferation at day 5 or 6, even in the absence of any activating signal. The spontaneously IL 2 proliferating cells are large lymphocytes, and they co-purify on a Percoll gradient in the large granular lymphocytes (third (LGL) fraction) together with the natural killer (NK) activity. When LGL were separated into NKH1 (an NK-specific surface marker)-positive and NKH1-negative cells by fluorescence-activated cell sorting (FACS), proliferating cells were mainly found in the NKH1-negative fraction. On the contrary, when cells from Percoll fraction 3 were separated into OKT3-negative and positive cells, the majority of the proliferating cells was found in the OKT3-positive cells. These results indicate that spontaneously IL 2 proliferating (SIP) cells most probably belong to the T cell lineage, but are distinct from NK cells. Additional analysis of Il 2 receptor induced in culture with IL 2 was performed by [ 125 I]anti-TAC binding and by [ 3 H]Il 2 binding. Scatchard analysis of [ 3 H]IL 2 binding, in the range of concentrations leading to the detection of high-affinity binding sites, showed an affinity constant similar to that of conventional phytohemagglutinin blasts. The results indicate that SIP cells are preactivated cells circulating in the blood. They are large cells and represent a very small proportion of circulating lymphocytes (0.3%). They express a subliminar amount of IL 2 receptor. Cultivated in the presence of IL 2, IL 2 receptor expression is enhanced to a detectable level, and the SIP cells begin to proliferate. These SIP cells could be activated T cells in the course of a current immune response or memory T cells present in every normal individual

  13. Pro-inflammatory signaling by IL-10 and IL-22: bad habit stirred up by interferons ?

    Directory of Open Access Journals (Sweden)

    Heiko eMühl

    2013-02-01

    Full Text Available Interleukin (IL-10 and IL-22 are key members of the IL-10 cytokine family that share characteristic properties such as defined structural features, usage of IL-10R2 as one receptor chain, and activation of signal transducer and activator of transcription (STAT-3 as dominant signaling mode. IL-10, formerly known as cytokine synthesis inhibitory factor, is key to deactivation of monocytes/macrophages and dendritic cells. Accordingly, pre-clinical studies document its anti-inflammatory capacity. However, the outcome of clinical trials assessing the therapeutic potential of IL-10 in prototypic inflammatory disorders has been disappointing. In contrast to IL-10, IL-22 acts primarily on non-leukocytic cells, in particular epithelial cells of intestine, skin, liver, and lung. STAT3-driven proliferation, anti-apoptosis, and anti-microbial tissue protection is regarded a principal function of IL-22 at host/environment interfaces. In this hypothesis article, hidden/underappreciated pro-inflammatory characteristics of IL-10 and IL-22 are outlined and related to cellular priming by type I interferon. It is tempting to speculate that an inherent inflammatory potential of IL-10 and IL-22 confines their usage in tissue protective therapy and beyond that determines in some patients efficacy of type I interferon treatment.

  14. Changes of serum cytokines levels after drug therapy in epileptic patients

    International Nuclear Information System (INIS)

    Xie Jianping; Li Suping; Xiong Gang

    2004-01-01

    Objective: To explore the role of the cytokines interleukin-2 (IL-2), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the neuroimmune modulation of epilepsy through measurement of the changes of the serum levels of the these cytokines after drug therapy in epileptic patients. Methods: Serum IL-2, IL-6, TNF-α levels were measured with RIA in 43 patients with epilepsy both before and after drug therapy for 3-6 months as well as 32 controls. Results: Before treatment, serum levels of these cytokines in the patients were significantly higher than those in the controls (p<0.001). After treatment, 18 of the 43 patients were regarded as treatment very successful, with attack numbers decreased more than 75%. Some of this group of patient had their serum cytokines levels significantly dropped down, but the mean level for the group as a whole did not change much. In the rest 25 patients with less successful result, changes were not significant with the levels increased in a few cases. Among the cytokines, levels of IL-2 were significantly positively correlated to those of IL-6 and TNF-α (r=0.47, p<0.01, r=0.55, p<0.01). Conclusion: Increased levels of the cytokines in the epileptic patients suggest an activated immune state. However, the changes of levels after therapy are not predictable and do not necessarily drop down significantly even with very successful treatment

  15. The association between soluble intercellular adhesion molecule-1 levels in drained dialysate and peritoneal injury in peritoneal dialysis.

    Science.gov (United States)

    Igarashi, Yusuke; Morishita, Yoshiyuki; Yoshizawa, Hiromichi; Imai, Reika; Imai, Toshimi; Hirahara, Ichiro; Akimoto, Tetsu; Ookawara, Susumu; Ishibashi, Kenichi; Muto, Shigeaki; Nagata, Daisuke

    2017-11-01

    Chronic inflammation of the peritoneum causes peritoneal injury in patients on peritoneal dialysis. Intercellular adhesion molecule-1 and its circulating form, soluble intercellular adhesion molecule-1, play pivotal roles in inflammation. However, their role in peritoneal injury is unclear. We measured changes in intercellular adhesion molecule-1 expression in the peritoneum of a peritoneal injury model in rats. The associations between soluble intercellular adhesion molecule-1 levels in drained dialysate and the solute transport rate (D/P-Cr and D/D0-glucose) determined by the peritoneal equilibration test, and matrix metalloproteinase-2 levels in drained dialysate were investigated in 94 peritoneal drained dialysate samples. Intercellular adhesion molecule-1 expression was increased in the peritoneum of rats with peritoneal injury. Soluble intercellular adhesion molecule-1 levels in drained dialysate were significantly positively correlated with D/P-Cr (r = .51, p molecule-1expression is increased in the peritoneum of a peritoneal injury model in the rat, and soluble intercellular adhesion molecule-1 levels in drained dialysate are associated with peritoneal injury in patients on peritoneal dialysis. These results suggest that soluble intercellular adhesion molecule-1 could be a novel biomarker of peritoneal injury in patients on peritoneal dialysis.

  16. CO2 solubility in aqueous solutions containing Na+, Ca2+, Cl−, SO42− and HCO3-: The effects of electrostricted water and ion hydration thermodynamics

    International Nuclear Information System (INIS)

    Gilbert, Kimberly; Bennett, Philip C.; Wolfe, Will; Zhang, Tongwei; Romanak, Katherine D.

    2016-01-01

    Dissolution of CO 2 into deep subsurface brines for carbon sequestration is regarded as one of the few viable means of reducing the amount of CO 2 entering the atmosphere. Ions in solution partially control the amount of CO 2 that dissolves, but the mechanisms of the ion's influence are not clearly understood and thus CO 2 solubility is difficult to predict. In this study, CO 2 solubility was experimentally determined in water, NaCl, CaCl 2 , Na 2 SO 4, and NaHCO 3 solutions and a mixed brine similar to the Bravo Dome natural CO 2 reservoir; ionic strengths ranged up to 3.4 molal, temperatures to 140 °C, and CO 2 pressures to 35.5 MPa. Increasing ionic strength decreased CO 2 solubility for all solutions when the salt type remained unchanged, but ionic strength was a poor predictor of CO 2 solubility in solutions with different salts. A new equation was developed to use ion hydration number to calculate the concentration of electrostricted water molecules in solution. Dissolved CO 2 was strongly correlated (R 2  = 0.96) to electrostricted water concentration. Strong correlations were also identified between CO 2 solubility and hydration enthalpy and hydration entropy. These linear correlation equations predicted CO 2 solubility within 1% of the Bravo Dome brine and within 10% of two mixed brines from literature (a 10 wt % NaCl + KCl + CaCl 2 brine and a natural Na + , Ca 2+ , Cl − type brine with minor amounts of Mg 2+ , K + , Sr 2+ and Br − ). - Highlights: • Measured CO 2 solubility in Na + , Cl − , HCO 3 - , Ca 2+ and SO 4 2− solutions at high PCO 2 . • A new equation calculates electrostricted water (mol/kgw) from hydration number. • CO 2 solubility strongly correlates (R 2  = 0.96) to electrostricted water. • Ion electrostriction of water limits its availability for CO 2 caging and solvation. • Correlations predict CO 2 solubility of several mixed brines to within 1–9%.

  17. Experimental murine fascioliasis derives early immune suppression with increased levels of TGF-β and IL-4.

    Science.gov (United States)

    Chung, Joon-Yong; Bae, Young-An; Yun, Doo-Hee; Yang, Hyun-Jong; Kong, Yoon

    2012-12-01

    In fascioliasis, T-helper 2 (Th2) responses predominate, while little is known regarding early immune phenomenon. We herein analyzed early immunophenotype changes of BALB/c, C57BL/6, and C3H/He mice experimentally infected with 5 Fasciola hepatica metacercariae. A remarkable expansion of CD19(+) B cells was observed as early as week 1 post-infection while CD4(+)/CD8(+) T cells were down-regulated. Accumulation of Mac1(+) cells with time after infection correlated well with splenomegaly of all mice strains tested. The expression of tumor necrosis factor (TNF)-α mRNA in splenocytes significantly decreased while that of IL-4 up-regulated. IL-1β expression was down-modulated in BALB/c and C57BL/6 mice, but not in C3H/He. Serum levels of transforming growth factor (TGF)-β were considerably elevated in all mice during 3 weeks of infection period. These collective results suggest that experimental murine fascioliasis might derive immune suppression with elevated levels of TGF-β and IL-4 during the early stages of infection.

  18. Cysteine protease antigens cleave CD123, the α subunit of murine IL-3 receptor, on basophils and suppress IL-3-mediated basophil expansion

    International Nuclear Information System (INIS)

    Nishikado, Hideto; Fujimura, Tsutomu; Taka, Hikari; Mineki, Reiko; Ogawa, Hideoki; Okumura, Ko; Takai, Toshiro

    2015-01-01

    Th2 type immune responses are essential for protective immunity against parasites and play crucial roles in allergic disorders. Helminth parasites secrete a variety of proteases for their infectious cycles including for host entry, tissue migration, and suppression of host immune effector cell function. Furthermore, a number of pathogen-derived antigens, as well as allergens such as papain, belong to the family of cysteine proteases. Although the link between protease activity and Th2 type immunity is well documented, the mechanisms by which proteases regulate host immune responses are largely unknown. Here, we demonstrate that the cysteine proteases papain and bromelain selectively cleave the α subunit of the IL-3 receptor (IL-3Rα/CD123) on the surface of murine basophils. The decrease in CD123 expression on the cell surface, and the degradation of the extracellular domain of recombinant CD123 were dependent on the protease activity of papain and bromelain. Pre-treatment of murine basophils with papain resulted in inhibition of IL-3-IL-3R signaling and suppressed IL-3- but not thymic stromal lymphopoietin-induced expansion of basophils in vitro. Our unexpected findings illuminate a novel mechanism for the regulation of basophil functions by protease antigens. Because IL-3 plays pivotal roles in the activation and proliferation of basophils and in protective immunity against helminth parasites, pathogen-derived proteases might contribute to the pathogenesis of infections by regulating IL-3-mediated functions in basophils. - Highlights: • We identified the murine IL3R as a novel target of papain-family cysteine proteases. • Papain-family cysteine proteases cleaved IL3Rα/CD123 on murine basophils. • Papain suppressed IL3- but not TSLP-induced expansion of murine basophils. • The inactivation of IL3R might be a strategy for pathogens to suppress host immunity

  19. Cysteine protease antigens cleave CD123, the α subunit of murine IL-3 receptor, on basophils and suppress IL-3-mediated basophil expansion

    Energy Technology Data Exchange (ETDEWEB)

    Nishikado, Hideto [Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo (Japan); Fujimura, Tsutomu; Taka, Hikari; Mineki, Reiko [Laboratory of Proteomics and Biomolecular Science, BioMedical Research Center, Juntendo University Graduate School of Medicine, Tokyo (Japan); Ogawa, Hideoki; Okumura, Ko [Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo (Japan); Takai, Toshiro, E-mail: t-takai@juntendo.ac.jp [Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo (Japan)

    2015-05-01

    Th2 type immune responses are essential for protective immunity against parasites and play crucial roles in allergic disorders. Helminth parasites secrete a variety of proteases for their infectious cycles including for host entry, tissue migration, and suppression of host immune effector cell function. Furthermore, a number of pathogen-derived antigens, as well as allergens such as papain, belong to the family of cysteine proteases. Although the link between protease activity and Th2 type immunity is well documented, the mechanisms by which proteases regulate host immune responses are largely unknown. Here, we demonstrate that the cysteine proteases papain and bromelain selectively cleave the α subunit of the IL-3 receptor (IL-3Rα/CD123) on the surface of murine basophils. The decrease in CD123 expression on the cell surface, and the degradation of the extracellular domain of recombinant CD123 were dependent on the protease activity of papain and bromelain. Pre-treatment of murine basophils with papain resulted in inhibition of IL-3-IL-3R signaling and suppressed IL-3- but not thymic stromal lymphopoietin-induced expansion of basophils in vitro. Our unexpected findings illuminate a novel mechanism for the regulation of basophil functions by protease antigens. Because IL-3 plays pivotal roles in the activation and proliferation of basophils and in protective immunity against helminth parasites, pathogen-derived proteases might contribute to the pathogenesis of infections by regulating IL-3-mediated functions in basophils. - Highlights: • We identified the murine IL3R as a novel target of papain-family cysteine proteases. • Papain-family cysteine proteases cleaved IL3Rα/CD123 on murine basophils. • Papain suppressed IL3- but not TSLP-induced expansion of murine basophils. • The inactivation of IL3R might be a strategy for pathogens to suppress host immunity.

  20. Interleukin-33 Receptor (ST2 Deficiency Improves the Outcome of Staphylococcus aureus-Induced Septic Arthritis

    Directory of Open Access Journals (Sweden)

    Larissa Staurengo-Ferrari

    2018-05-01

    Full Text Available The ST2 receptor is a member of the Toll/IL-1R superfamily and interleukin-33 (IL-33 is its agonist. Recently, it has been demonstrated that IL-33/ST2 axis plays key roles in inflammation and immune mediated diseases. Here, we investigated the effect of ST2 deficiency in Staphylococcus aureus-induced septic arthritis physiopathology. Synovial fluid samples from septic arthritis and osteoarthritis individuals were assessed regarding IL-33 and soluble (s ST2 levels. The IL-33 levels in samples from synovial fluid were significantly increased, whereas no sST2 levels were detected in patients with septic arthritis when compared with osteoarthritis individuals. The intra-articular injection of 1 × 107 colony-forming unity/10 μl of S. aureus American Type Culture Collection 6538 in wild-type (WT mice induced IL-33 and sST2 production with a profile resembling the observation in the synovial fluid of septic arthritis patients. Data using WT, and ST2 deficient (−/− and interferon-γ (IFN-γ−/− mice showed that ST2 deficiency shifts the immune balance toward a type 1 immune response that contributes to eliminating the infection due to enhanced microbicide effect via NO production by neutrophils and macrophages. In fact, the treatment of ST2−/− bone marrow-derived macrophage cells with anti-IFN-γ abrogates the beneficial phenotype in the absence of ST2, which confirms that ST2 deficiency leads to IFN-γ expression and boosts the bacterial killing activity of macrophages against S. aureus. In agreement, WT cells achieved similar immune response to ST2 deficiency by IFN-γ treatment. The present results unveil a previously unrecognized beneficial effect of ST2 deficiency in S. aureus-induced septic arthritis.