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Sample records for disease-associated human il-4

  1. Pathogenicity of a disease-associated human IL-4 receptor allele in experimental asthma.

    Science.gov (United States)

    Tachdjian, Raffi; Mathias, Clinton; Al Khatib, Shadi; Bryce, Paul J; Kim, Hong S; Blaeser, Frank; O'Connor, Brian D; Rzymkiewicz, Danuta; Chen, Andrew; Holtzman, Michael J; Hershey, Gurjit K; Garn, Holger; Harb, Hani; Renz, Harald; Oettgen, Hans C; Chatila, Talal A

    2009-09-28

    Polymorphisms in the interleukin-4 receptor alpha chain (IL-4R alpha) have been linked to asthma incidence and severity, but a causal relationship has remained uncertain. In particular, a glutamine to arginine substitution at position 576 (Q576R) of IL-4R alpha has been associated with severe asthma, especially in African Americans. We show that mice carrying the Q576R polymorphism exhibited intense allergen-induced airway inflammation and remodeling. The Q576R polymorphism did not affect proximal signal transducer and activator of transcription (STAT) 6 activation, but synergized with STAT6 in a gene target- and tissue-specific manner to mediate heightened expression of a subset of IL-4- and IL-13-responsive genes involved in allergic inflammation. Our findings indicate that the Q576R polymorphism directly promotes asthma in carrier populations by selectively augmenting IL-4R alpha-dependent signaling.

  2. Expression of IL-4 receptor on human T and B lymphocytes.

    Science.gov (United States)

    Zola, H; Flego, L; Weedon, H

    1993-08-01

    The expression of the interleukin-4 receptor on human blood and tonsil lymphocytes has been studied using a monoclonal antibody and high-sensitivity immunofluorescence flow cytometry. While no receptor expression could be detected on circulating or tonsil T cells, a subset of B cells was shown to express the receptor. The IL-4R-positive B cells in tonsil had a phenotype suggesting that they included both germinal centre B cells and B cells outside the germinal centre. The subset of B cells in the blood that expressed the receptor included CD23-positive B cells. Activation of tonsil B cells using anti-IgM, IL-4, IL-2, or combinations of these reagents led to increases in IL-4R expression, but these changes were small compared to changes in the expression of IL-2R p55 (CD25), a known marker of activation. Similarly, activation of T cells led to low-level expression of IL-4R, with IL-4 itself up-regulating IL-4R, especially in CD4 cells. The majority of chronic lymphocytic leukaemia samples were positive for IL-4R expression, whilst most other leukemic samples were negative.

  3. IL-4 induces cAMP and cGMP in human monocytic cells

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    B. Dugas

    1995-01-01

    Full Text Available Human monocytes, preincubated with IFN-γ respond to IL-4 by a cGMP increase through activation of an inducible NO synthase. Here, IL-4 was found to induce an accumulation of cGMP (1 – 3 min and cAMP (20 – 25 min in unstimulated monocytes. This was impaired with NOS inhibitors, but also with EGTA and calcium/calmodulin inhibitors. These results suggest that: (1 IL-4 may stimulate different NOS isoforms in resting and IFN-γ activated monocytes, and (2 cAMP accumulation may be partially dependent on the NO pathway. By RT-PCR, a type III constitutive NOS mRNA was detected in U937 monocytic cells. IL-4 also increased the [Ca2+]i in these cells. Different NOS may thus be expressed in monocytic cells depending on their differentiation and the signals they receive.

  4. Growth and gene expression are predominantly controlled by distinct regions of the human IL-4 receptor.

    Science.gov (United States)

    Ryan, J J; McReynolds, L J; Keegan, A; Wang, L H; Garfein, E; Rothman, P; Nelms, K; Paul, W E

    1996-02-01

    IL-4 causes hematopoietic cells to proliferate and express a series of genes, including CD23. We examined whether IL-4-mediated growth, as measured by 4PS phosphorylation, and gene induction were similarly controlled. Studies of M12.4.1 cells expressing human IL-4R truncation mutants indicated that the region between amino acids 557-657 is necessary for full gene expression, which correlated with Stat6 DNA binding activity. This region was not required for 4PS phosphorylation. Tyrosine-to-phenylalanine mutations in the interval between amino acids 557-657 revealed that as long as one tyrosine remained unmutated, CD23 was fully induced. When all three tyrosines were mutated, the receptor was unable to induce CD23. The results indicate that growth regulation and gene expression are principally controlled by distinct regions of IL-4R.

  5. Further evidence for a human B cell activating factor distinct from IL-4.

    Science.gov (United States)

    Diu, A; Février, M; Mollier, P; Charron, D; Banchereau, J; Reinherz, E L; Thèze, J

    1990-01-01

    Supernatants from activated human T cell clones were previously shown to contain B cell-activating factor (BCAF), an activity which results in polyclonal resting B cell stimulation. In the present study, we investigate the relationship between this activity and human interleukin-4 which was also shown to act on resting B cells. The supernatant of the T cell clone TT9 contains IL-4 but anti-IL-4 antiserum does not affect the response of B cells as measured by thymidine uptake or cell volume increase. Furthermore, IL-4 induces Fc epsilon-receptor (CD23) expression on 30% of unstimulated human B cells, whereas BCAF-containing supernatants from clone P2, that do not contain detectable amounts of IL-4, promote B cell proliferation without inducing CD23 expression. Our results therefore establish that IL-4 and BCAF are distinct activities and suggest that they trigger different activation pathways in human B cells. In addition, culture of B cells with T cell supernatants for 72 hr induces a three- to fourfold increase in the expression of HLA-DR, -DP, and -DQ antigens in 50% of B cells. The addition of inhibiting concentrations of anti-IFN-gamma, LT, or IL-4 antisera to the cultures does not change these results. Finally, 30% of B cells cultured with T cell supernatants leave the G1 phase of the cell cycle and 20% reach mitosis. Taken together, our findings further support the existence of a B cell-activating factor responsible for the activation of resting human B cells.

  6. DMPD: Differential responses of human monocytes and macrophages to IL-4 and IL-13. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10534111 Differential responses of human monocytes and macrophages to IL-4 and IL-1...):575-8. (.png) (.svg) (.html) (.csml) Show Differential responses of human monocytes and macrophages to IL-...4 and IL-13. PubmedID 10534111 Title Differential responses of human monocytes an

  7. IL-4 Modulates CCL11 and CCL20 Productions from IL-1β-Stimulated Human Periodontal Ligament Cells

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    Yoshitaka Hosokawa

    2016-01-01

    Full Text Available Background/Aims: IL-4 is a multifunctional cytokine that is related with the pathological conditions of periodontal disease. However, it is uncertain whether IL-4 could control T cells migration in periodontal lesions. The aim of this study was to examine the effects of IL-4 on CCL11, which is a Th2-type chemokine, and CCL20, which is related with Th17 cells migration, productions from human periodontal ligament cells (HPDLCs. Methods: CCL20 and CCL11 productions from HPDLCs were monitored by ELISA. Western blot analysis was performed to detect phosphorylations of signal transduction molecules in HPDLCs. Results: IL-1β could induce both CCL11 and CCL20 productions in HPDLCs. IL-4 enhanced CCL11 productions from IL-1β-stimulated HPDLCs, though IL-4 inhibited CCL20 production. Western blot analysis showed that protein kinase B (Akt and signal transducer and activator of transcription (STAT6 pathways were highly activated in IL-4/IL-1β-stimulated HPDLCs. Akt and STAT6 inhibitors decreased CCL11 production, but enhanced CCL20 production in HPDLCs stimulated with IL-4 and IL-1β. Conclusions: These results mean that IL-4 enhanced Th2 cells migration in periodontal lesion to induce CCL11 production from HPDLCs. On the other hand, IL-4 inhibits Th17 cells accumulation in periodontally diseased tissues to inhibit CCL20 production. Therefore, IL-4 is positively related with the pathogenesis of periodontal disease to control chemokine productions in periodontal lesions.

  8. EVALUATION OF THE ANTITUMOR ACTIVITY OF HUMAN IL-4 BY IN VITRO AND IN V1VO ASSAYS

    Institute of Scientific and Technical Information of China (English)

    王彤钢; 陈慰峰

    1994-01-01

    The characteristics of rhuIL-4 induced cytotoxicity was detected in vitro by using 51 Cr release assay and the anti-tumor activity of rhuIL-4 induced killer cell was evaluated in vivo by using a human tumor model in nudemice.huIL-4 can induce LAK activity from peripheral blood lymphocytes(PBMC) stimulated with phytohemagglutinin(PHA).Compared with the LAK activity induced by rhuIL-2,the cytotoxicity of the killer cells induced by rhuIL-4 to K562 and Raji cells was lower ,but that to TBL-E,a human lymphoid leukemia cell line established in our laboratory,and PHA-activated blast cells(PHA-blasts) was of similar magnitude.In the cytotoxicity assay using PHA-blasts,the addition of PHA increased the IL-4 induced killer cell cytotoxicity by 131%,but had no effect on IL-2-induced ki8ller cell cytotoxicity.This implies that IL-4 mainly induces CTL-like activity,while IL-2 mainly induces NK-like activity,An experimental human tumor model in nude mice was established by injection of TBL-E human leukemia cells.The anti-tumor activity of rhuIL-4 was evaluated by injection of haman LAK cells induced from PHA-blasts by rhuIL-2+rhuIL-4 and human cytokines into tumor-bearing nude mice.The results showed that human LAK cells effectively inhibit the tumorigenicity of TBL-E cells in nude mice with an inhibition rate of 61%.The antitumor effect of rhuIL-2 was better than that of rIL-4 ,and the antitumor effect of rhuIL-2+rhuIL-4 was similar to that of rhuIL-2 ,though the former delayed the occurence of tumors.Our data imply the potential application of human IL-4 in clinic,and provide an animal model to evaluate the anti-tumor activity of human cytokine(s) with species specificity.

  9. Evaluation of the correlation and reproducibility between histamine, IL-4, and IL-13 release from human basophils.

    OpenAIRE

    Nahid Eskandari; Reza Bastan; Maryam Ahmadi; Peachell, Peter T

    2014-01-01

    Human basophils play a key role in allergic diseases such as asthma and in a variety of immunological disorders. The generation of IL-4 and IL-13 can be induced from basophil by IgE-mediated and non-IgE-mediated mechanisms. Time and stimulus-dependent differences in the regulation of these cytokines could have relevance to their biological effects. The aim of the present study was activation of basophils in order to evaluate the extent of histamine, IL-4, and IL-13 generations. Basophil-enric...

  10. Genetic programs expressed in resting and IL-4 alternatively activated mouse and human macrophages : similarities and differences

    NARCIS (Netherlands)

    Martinez, Fernando O.; Helming, Laura; Milde, Ronny; Varin, Audrey; Melgert, Barbro N.; Draijer, Christina; Thomas, Benjamin; Fabbri, Marco; Crawshaw, Anjali; Ho, Ling Pei; Ten Hacken, Nick H.; Jimenez, Viviana Cobos; Kootstra, Neeltje A.; Hamann, Jorg; Greaves, David R.; Locati, Massimo; Mantovani, Alberto; Gordon, Siamon

    2013-01-01

    The molecular repertoire of macrophages in health and disease can provide novel biomarkers for diagnosis, prognosis, and treatment. Th2-IL-4-activated macrophages (M2) have been associated with important diseases in mice, yet no specific markers are available for their detection in human tissues. Al

  11. IFN-γ, IL-4 and IL-13 modulate responsiveness of human airway smooth muscle cells to IL-13

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    Michoud Marie-Claire

    2008-12-01

    Full Text Available Abstract Background IL-13 is a critical mediator of allergic asthma and associated airway hyperresponsiveness. IL-13 acts through a receptor complex comprised of IL-13Rα1 and IL-4Rα subunits with subsequent activation of signal transducer and activator of transcription 6 (STAT6. The IL-13Rα2 receptor may act as a decoy receptor. In human airway smooth muscle (HASM cells, IL-13 enhances cellular proliferation, calcium responses to agonists and induces eotaxin production. We investigated the effects of pre-treatment with IL-4, IL-13 and IFN-γ on the responses of HASM cells to IL-13. Methods Cultured HASM were examined for expression of IL-13 receptor subunits using polymerase chain reaction, immunofluorescence microscopy and flow cytometry. Effects of cytokine pre-treatment on IL-13-induced cell responses were assessed by looking at STAT6 phosphorylation using Western blot, eotaxin secretion and calcium responses to histamine. Results IL-13Rα1, IL-4Rα and IL-13Rα2 subunits were expressed on HASM cells. IL-13 induced phosphorylation of STAT6 which reached a maximum by 30 minutes. Pre-treatment with IL-4, IL-13 and, to a lesser degree, IFN-γ reduced peak STAT6 phosphorylation in response to IL-13. IL-13, but not IFN-γ, pre-treatment abrogated IL-13-induced eotaxin secretion. Pre-treatment with IL-4 or IL-13 abrogated IL-13-induced augmentation of the calcium transient evoked by histamine. Cytokine pre-treatment did not affect expression of IL-13Rα1 and IL-4Rα but increased expression of IL-13Rα2. An anti-IL-13Rα2 neutralizing antibody did not prevent the cytokine pre-treatment effects on STAT6 phosphorylation. Cytokine pre-treatment increased SOCS-1, but not SOCS-3, mRNA expression which was not associated with significant increases in protein expression. Conclusion Pre-treatment with IL-4 and IL-13, but not IFN-γ, induced desensitization of the HASM cells to IL-13 as measured by eotaxin secretion and calcium transients to histamine

  12. Evaluation of the correlation and reproducibility between histamine, IL-4, and IL-13 release from human basophils.

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    Nahid Eskandari

    2014-06-01

    Full Text Available Human basophils play a key role in allergic diseases such as asthma and in a variety of immunological disorders. The generation of IL-4 and IL-13 can be induced from basophil by IgE-mediated and non-IgE-mediated mechanisms. Time and stimulus-dependent differences in the regulation of these cytokines could have relevance to their biological effects. The aim of the present study was activation of basophils in order to evaluate the extent of histamine, IL-4, and IL-13 generations. Basophil-enriched suspensions were prepared by Percoll gradients. The release of histamine and cytokines was assessed after activation with either anti-human IgE (1/1000 or 1/10000, 4 h or 24 h or IL-3 (100 ng/ ml, 24 h. Results were analysed statistically, using ANOVA test. Using anti-IgE, there was no significant correlation between the extent of either IL-4 (r=0.24, p=0.35 or IL-13 (r=0.47, p=0.098 and histamine release. Using IL-3 as stimulator, results showed that the extent of IL-13 correlated with histamine release(r=0.44, p=0.036. There was no correlation between the extent of IL-4 and the degree of either histamine (r=0.077, p=0.72 or IL-13 (r=0.162, p=0.5. The reproducibility of cytokines isolated from the same donor (on different occasions indicated that the ability of anti-IgE to induce cytokines was consistently similar for a given donor. Our data showed that the pathways leading to IL-3-triggering histamine release and IL-13 generation show similarity. Donor-dependent differences may be responsible for this wide range in the extent of releasibility. The ability of IL-3 to release cytokines from basophils showed a wider range.

  13. Evaluation of the correlation and reproducibility between histamine, IL-4, and IL-13 release from human basophils.

    Science.gov (United States)

    Eskandari, Nahid; Bastan, Reza; Ahmadi, Maryam; Peachell, Peter T

    2014-06-01

    Human basophils play a key role in allergic diseases such as asthma and in a variety of immunological disorders. The generation of IL-4 and IL-13 can be induced from basophil by IgE-mediated and non-IgE-mediated mechanisms. Time and stimulus-dependent differences in the regulation of these cytokines could have relevance to their biological effects. The aim of the present study was activation of basophils in order to evaluate the extent of histamine, IL-4, and IL-13 generations. Basophil-enriched suspensions were prepared by Percoll gradients. The release of histamine and cytokines was assessed after activation with either anti-human IgE (1/1000 or 1/10000, 4 h or 24 h) or IL-3 (100 ng/ ml, 24 h). Results were analysed statistically, using ANOVA test. Using anti-IgE, there was no significant correlation between the extent of either IL-4 (r=0.24, p=0.35) or IL-13 (r=0.47, p=0.098) and histamine release. Using IL-3 as stimulator, results showed that the extent of IL-13 correlated with histamine release(r=0.44, p=0.036). There was no correlation between the extent of IL-4 and the degree of either histamine (r=0.077, p=0.72) or IL-13 (r=0.162, p=0.5). The reproducibility of cytokines isolated from the same donor (on different occasions) indicated that the ability of anti-IgE to induce cytokines was consistently similar for a given donor. Our data showed that the pathways leading to IL-3-triggering histamine release and IL-13 generation show similarity. Donor-dependent differences may be responsible for this wide range in the extent of releasibility. The ability of IL-3 to release cytokines from basophils showed a wider range.

  14. Identification and Characterization of a Novel IL-4 Receptor α Chain (IL-4Rα Antagonist to Inhibit IL-4 Signalling

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    Nayyar Ahmed

    2015-05-01

    Full Text Available Background/Aims: In recent times, allergy has become a financial, physical and psychological burden to the society as a whole. In allergic cascades, cytokine IL-4 binds to IL-4 receptor (IL-4R, consequently producing allergen-specific IgE antibodies by B cells. In addition, among other functions, IL-4 is also responsible for B and T cell proliferation and differentiation. Hence, characterization of novel antagonists that inhibit IL-4 signalling forms the overall aim of this study. Methods: Phage display was used to screen a random 12-mer synthetic peptide library with a human IL-4Rα to identify peptide candidates. Once identified, the peptides were commercially synthesized and used for in vitro immunoassays. Results: We have successfully used phage display to identify M13 phage clones that demonstrated specific binding to IL-4Rα. The peptide N1 was synthesized for use in ELISA, demonstrating significant binding to IL-4Rα and inhibiting interaction with cytokine IL-4. Furthermore, the peptide was tested in a transfected HEK-Blue IL-4 reporter cell line model, which produces alkaline phosphatase (AP. QUANTI-Blue, a substrate, breaks down in the presence of AP producing a blue coloration. Using this colorimetric analysis, >50% inhibition of IL-4 signalling was achieved. Conclusion: We have successfully identified and characterised a synthetic peptide antagonist against IL-4Rα, which effectively inhibits IL-4 interaction with the IL-4Rα in vitro. Since IL-4 interaction with IL-4Rα is a common pathway for many allergies, a prophylactic treatment can be devised by inhibiting this interaction for future treatment of allergies.

  15. Analysis of allelic expression patterns of IL-2, IL-3, IL-4, and IL-13 in human CD4+ T cell clones.

    NARCIS (Netherlands)

    Bayley, J.P.; Bakker, AM; Kaijzel, EL; Wierenga, EA; Pouw Kraan, van der C.T.M.; Huizinga, T.W.; Verweij, C.L.

    2003-01-01

    The occurrence of monoallelic expression of cytokine genes in single cells has been convincingly demonstrated, but there have been few reports of this phenomenon in T cell clones. Here we describe studies on the expression of alleles of the human genes encoding IL-2, IL-3, IL-4, and IL-13 in human C

  16. Research Upregulation of CD23 (FcεRII Expression in Human Airway Smooth Muscle Cells (huASMC in Response to IL-4, GM-CSF, and IL-4/GM-CSF

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    Lew D Betty

    2005-05-01

    Full Text Available Abstract Background Airway smooth muscle cells play a key role in remodeling that contributes to airway hyperreactivity. Airway smooth muscle remodeling includes hypertrophy and hyperplasia. It has been previously shown that the expression of CD23 on ASMC in rabbits can be induced by the IgE component of the atopic serum. We examined if other components of atopic serum are capable of inducing CD23 expression independent of IgE. Methods Serum starved huASMC were stimulated with either IL-4, GM-CSF, IL-13, IL-5, PGD2, LTD4, tryptase or a combination of IL-4, IL-5, IL-13 each with GM-CSF for a period of 24 h. CD23 expression was analyzed by flow cytometry, western blot, and indirect immunofluorescence. Results The CD23 protein expression was upregulated in huASMC in response to IL-4, GM-CSF, and IL-4/GM-CSF. The percentage of cells with increased fluorescence intensity above the control was 25.1 ± 4.2% (IL-4, 15.6 ± 2.7% (GM-CSF and 32.9 ± 13.9% (IL-4/GMCSF combination(n = 3. The protein content of IL-4/GMCSF stimulated cells was significantly elevated. Expression of CD23 in response to IL-4, GM-CSF, IL-4/GM-CSF was accompanied by changes in cell morphology including depolymerization of isoactin fibers, cell spreading, and membrane ruffling. Western blot revealed abundant expression of the IL-4Rα and a low level expression of IL-2Rγc in huASMC. Stimulation with IL-4 resulted in the phosphorylation of STAT-6 and an increase in the expression of the IL-2Rγc. Conclusion CD23 on huASMC is upregulated by IL-4, GM-CSF, and IL-4/GM-CSF. The expression of CD23 is accompanied by an increase in cell volume and an increase in protein content per cell, suggesting hypertrophy. Upregulation of CD23 by IL-4/GM-CSF results in phenotypic changes in huASMC that could play a role in cell migration or a change in the synthetic function of the cells. Upregulation of CD23 in huASMC by IL-4 and GM-CSF can contribute to changes in huASMC and may provide an avenue

  17. Immunoglobulin superantigen protein L induces IL-4 and IL-13 secretion from human Fc epsilon RI+ cells through interaction with the kappa light chains of IgE.

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    Genovese, Arturo; Borgia, Guglielmo; Björck, Lars; Petraroli, Angelica; de Paulis, Amato; Piazza, Marcello; Marone, Gianni

    2003-02-15

    Peptostreptococcus magnus protein L is a multidomain bacterial surface protein that correlates with virulence. It consists of up to five homologous Ig-binding domains (B1-B5) that interact with the variable domain of Ig kappa L chains. Intact protein L stimulates the synthesis and the release of IL-4 and IL-13 from human basophils in vitro. A protein L fragment covering the Ig-binding domains B1-B4 also induced IL-4 and IL-13 release from basophils. There was an excellent correlation (r(s) = 0.82; p ADZ (kappa chains) blocked both anti-IgE- and protein L-induced secretion. Cyclosporin A, but not cyclosporin H, inhibited protein L-induced release of IL-4 and IL-13 from basophils. Thus, protein L acts as a bacterial Ig superantigen to induce the synthesis and release of IL-4 and IL-13 from basophils by interacting with kappa L chains of the IgE isotype.

  18. Distribution of polymorphisms IL4-590 C/T and IL4 RP2 in the human populations of Madeira, Azores, Portugal, Cape Verde and Guinea-Bissau.

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    Berenguer, Anabela G; Câmara, Rita A; Brehm, António D; Oliveira, Susana; Fernandes, Ana T

    2012-01-01

    The IL4 gene is located on chromosome 5q23.3-31.2. Polymorphisms within this cytokine gene, like the derivative allele T of IL4-590, have been reported as being associated to elevated IgE serum levels and asthma. In the present work, the allelic and genotypic frequency of the IL4-590 and IL4 RP2 polymorphisms was carried out in 599 individuals from Madeira, Azores, Portugal mainland, Cape Verde and Guinea-Bissau and in a sample of 101 asthmatics from Madeira population. In all populations the polymorphisms were in LD and presented a significant dissimilar allelic and genotypic distribution (pMadeira when compared to Azores. Significant differences regarding both loci were found between Madeira population and the group of asthmatics. Genotype 183183TT frequency is higher for African populations while 253253CC prevails in Caucasian populations. The existence of a Hardy-Weinberg Disequilibrium in Guinea-Bissau population not observed in neutral markers leads to the hypothesis of natural selection occurring in these loci probably associated to a rapid population growth an hypothesis strengthened by neutral STRs D5S818 and CSF1PO gene diversity.

  19. Cytokines TNF-α, IL-6, IL-17F, and IL-4 Differentially Affect Osteogenic Differentiation of Human Adipose Stem Cells

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    Angela P. Bastidas-Coral

    2016-01-01

    Full Text Available During the initial stages of bone repair, proinflammatory cytokines are released within the injury site, quickly followed by a shift to anti-inflammatory cytokines. The effect of pro- and anti-inflammatory cytokines on osteogenic differentiation of mesenchymal stem cells is controversial. Here, we investigated the effect of the proinflammatory cytokines TNF-α, IL-6, IL-8, and IL-17F and the anti-inflammatory cytokine IL-4 on proliferation and osteogenic differentiation of human adipose stem cells (hASCs. hASCs were treated with TNF-α, IL-6, IL-8, IL-17F, or IL-4 (10 ng/mL for 72 h mimicking bone repair. TNF-α reduced collagen type I gene expression but increased hASC proliferation and ALP activity. IL-6 also strongly enhanced ALP activity (18-fold, as well as bone nodule formation by hASCs. IL-8 did not affect proliferation or osteogenic gene expression but reduced bone nodule formation. IL-17F decreased hASC proliferation but enhanced ALP activity. IL-4 enhanced osteocalcin gene expression and ALP activity but reduced RUNX2 gene expression and bone nodule formation. In conclusion, all cytokines studied have both enhancing and reducing effects on osteogenic differentiation of hASCs, even when applied for 72 h only. Some cytokines, specifically IL-6, may be suitable to induce osteogenic differentiation of mesenchymal stem cells as a strategy for enhancing bone repair.

  20. Development of a human IgG4 bispecific antibody for dual targeting of interleukin-4 (IL-4) and interleukin-13 (IL-13) cytokines.

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    Spiess, Christoph; Bevers, Jack; Jackman, Janet; Chiang, Nancy; Nakamura, Gerald; Dillon, Michael; Liu, Hongbin; Molina, Patricia; Elliott, J Michael; Shatz, Whitney; Scheer, Justin M; Giese, Glen; Persson, Josefine; Zhang, Yin; Dennis, Mark S; Giulianotti, James; Gupta, Prateek; Reilly, Dorothea; Palma, Enzo; Wang, Jianyong; Stefanich, Eric; Scheerens, Heleen; Fuh, Germaine; Wu, Lawren C

    2013-09-13

    Human bispecific antibodies have great potential for the treatment of human diseases. Although human IgG1 bispecific antibodies have been generated, few attempts have been reported in the scientific literature that extend bispecific antibodies to other human antibody isotypes. In this paper, we report our work expanding the knobs-into-holes bispecific antibody technology to the human IgG4 isotype. We apply this approach to generate a bispecific antibody that targets IL-4 and IL-13, two cytokines that play roles in type 2 inflammation. We show that IgG4 bispecific antibodies can be generated in large quantities with equivalent efficiency and quality and have comparable pharmacokinetic properties and lung partitioning, compared with the IgG1 isotype. This work broadens the range of published therapeutic bispecific antibodies with natural surface architecture and provides additional options for the generation of bispecific antibodies with differing effector functions through the use of different antibody isotypes.

  1. FRNK negatively regulates IL-4-mediated inflammation.

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    Sharma, Ritu; Colarusso, Pina; Zhang, Hong; Stevens, Katarzyna M; Patel, Kamala D

    2015-02-15

    Focal adhesion kinase (FAK)-related nonkinase (PTK2 isoform 6 in humans, hereafter referred to as FRNK) is a cytoskeletal regulatory protein that has recently been shown to dampen lung fibrosis, yet its role in inflammation is unknown. Here, we show for the first time that expression of FRNK negatively regulates IL-4-mediated inflammation in a human model of eosinophil recruitment. Mechanistically, FRNK blocks eosinophil accumulation, firm adhesion and transmigration by preventing transcription and protein expression of VCAM-1 and CCL26. IL-4 activates STAT6 to induce VCAM-1 and CCL26 transcription. We now show that IL-4 also increases GATA6 to induce VCAM-1 expression. FRNK blocks IL-4-induced GATA6 transcription but has little effect on GATA6 protein expression and no effect on STAT6 activation. FRNK can block FAK or Pyk2 signaling and we, thus, downregulated these proteins using siRNA to determine whether signaling from either protein is involved in the regulation of VCAM-1 and CCL26. Knockdown of FAK, Pyk2 or both had no effect on VCAM-1 or CCL26 expression, which suggests that FRNK acts independently of FAK and Pyk2 signaling. Finally, we found that IL-4 induces the late expression of endogenous FRNK. In summary, FRNK represents a novel mechanism to negatively regulate IL-4-mediated inflammation.

  2. Linking disease associations with regulatory information in the human genome

    KAUST Repository

    Schaub, M. A.

    2012-09-01

    Genome-wide association studies have been successful in identifying single nucleotide polymorphisms (SNPs) associated with a large number of phenotypes. However, an associated SNP is likely part of a larger region of linkage disequilibrium. This makes it difficult to precisely identify the SNPs that have a biological link with the phenotype. We have systematically investigated the association of multiple types of ENCODE data with disease-associated SNPs and show that there is significant enrichment for functional SNPs among the currently identified associations. This enrichment is strongest when integrating multiple sources of functional information and when highest confidence disease-associated SNPs are used. We propose an approach that integrates multiple types of functional data generated by the ENCODE Consortium to help identify "functional SNPs" that may be associated with the disease phenotype. Our approach generates putative functional annotations for up to 80% of all previously reported associations. We show that for most associations, the functional SNP most strongly supported by experimental evidence is a SNP in linkage disequilibrium with the reported association rather than the reported SNP itself. Our results show that the experimental data sets generated by the ENCODE Consortium can be successfully used to suggest functional hypotheses for variants associated with diseases and other phenotypes.

  3. Defective IL-4/Stat6 Signaling Correlates with Increased Apoptosis of Human EBV-lymphoblastoid B Cells and Mouse Spleen Cells

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    1Introduction IL-4-induced Stat6 (Signal transducer and activator of transcription 6) pathway is active in many cell types including cancer cells and immune cells which plays an important role in cell differenciation/growth and resistance to apoptosis~([1]). IL-4/Stat6 signaling up-regulates cell surface moleculi suchas CD23, MHC class II and IL-4Rα, and down-regulates proinflammatory cytokines,i.e, IL-12 and TNFα.Stat6 can be spontaneously activated in Hodgkin's lymphoma and other tumors, suggesting its...

  4. Association of polymorphisms in the human IL4 and IL5 genes with atopic bronchial asthma and severity of the disease.

    Science.gov (United States)

    Freidin, Maxim B; Kobyakova, Olga S; Ogorodova, Ludmila M; Puzyrev, Valery P

    2003-01-01

    Two polymorphisms in the IL4 (G/C 3'-UTR) and IL5 (C-703T) genes were studied in a sample of families whose probands had atopic bronchial asthma (BA) (66 families, n = 183) and in a group of non-cognate individuals with the severe form of the disease (n = 34). The samples were collected from the Russian population in the city of Tomsk (Russia). Using the transmission/disequilibrium test (TDT), a significant association of allele C-703 IL5 with BA was established (TDT = 4.923, p = 0.007 +/- 0.0007). The analysis of 40 individuals with mild asthma and 49 patients with the severe form of the disease revealed a negative association of genotype GG IL4 (OR = 0.39, 95% CI = 0.15-0.99, p = 0.035), and also a trend towards a positive association of the GC IL4 genotype (OR = 2.52, 95% CI = 0.98-6.57, p = 0.052) with mild BA. There was a concordance of the clinical classification of BA severity with the 'genotype' (McNemar's chi(2) test with continuity correction constituted 0.03, d.f. = 1, p = 0.859). These results suggest that polymorphisms in the IL4 and IL5 genes contribute to the susceptibility to atopic BA and could determine the clinical course of the disease.

  5. Cardiac Disease Associated with Human Immunodeficiency Virus Infection.

    Science.gov (United States)

    Bloomfield, Gerald S; Leung, Claudia

    2017-02-01

    Over the last 2 decades human immunodeficiency virus (HIV) infection has become a chronic disease requiring long-term management. Aging, antiretroviral therapy, chronic inflammation, and several other factors contribute to the increased risk of cardiovascular disease in patients infected with HIV. In low-income and middle-income countries where antiretroviral therapy access is limited, cardiac disease is most commonly related to opportunistic infections and end-stage manifestations of HIV/acquired immunodeficiency syndrome, including HIV-associated cardiomyopathy, pericarditis, and pulmonary arterial hypertension. Cardiovascular screening, prevention, and risk factor management are important factors in the management of patients infected with HIV worldwide. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Interstitial lung disease associated with human papillomavirus vaccination

    Directory of Open Access Journals (Sweden)

    Yasushi Yamamoto

    2015-01-01

    Full Text Available Vaccinations against the human papillomavirus (HPV have been recommended for the prevention of cervical cancer. HPV-16/18 AS04-adjuvanted vaccines (Cervarix are said to have favourable safety profiles. Interstitial lung diseases (ILDs can occur following exposure to a drug or a biological agent. We report a case of ILD associated with a Cervarix vaccination. A woman in her 40's, with a history of conisation, received three inoculations of Cervarix. Three months later, she presented with a cough and shortness of breath. Findings from a computed tomography of the chest and a transbronchial lung biopsy were consistent with non-specific interstitial pneumonia. Workup eliminated all other causes of the ILD, except for the vaccination. Over the 11 months of the follow-up period, her symptoms resolved without steroid therapy. The onset and spontaneous resolution of the ILD showed a chronological association with the HPV vaccination. The semi-quantitative algorithm revealed that the likelihood of an adverse drug reaction to Cervarix was “Probable”. The outcome was relatively good, but more attention should be paid to a potential risk for HPV vaccinations to cause ILDs. Wherever possible, chest radiographic examinations should be performed in order not to overlook any ILDs.

  7. Constituents of the anti-asthma herbal formula ASHMITM synergistically inhibit IL-4 and IL-5secretion by murine Th2 memory cells, and eotaxin by human lung fibroblasts in vitro

    Institute of Scientific and Technical Information of China (English)

    Bolleddula Javaprakasam; Nan Yang; Ming-Chun Wen; Rong Wang; Joseph Goldfarb; Hugh Sampson; Xiu-Min Li

    2013-01-01

    OBJECITVE:Anti-asthma herbal medicine intervention (ASHMITM),a combination of three traditional Chinese medicinal herbs developed in our laboratory,has demonstrated efficacy in both mouse models of allergic asthma,and a double-blind placebo-controlled clinical trial in patients with asthma.This study was designed to determine if the anti-inflammatory effects of individual herbal constituents of ASHMITM exhibited synergy.METHODS:Effects of ASHMI and its components aqueous extracts of Lingzhi (Ganoderma lucidum),Kushen (Sophora flavescens) and Gancao (Glycyrrhiza uralensis),on Th2 cytokine secretion by murine memory Th2 cells (D10.G4.1) and eotaxin-1 secretion by human lung fibroblast (HLF-1) cells were determined by measuring levels in culture supernatants by enzymelinked immunosorbent assay.Potential synergistic effects were determined by computing interaction indices from concentration-effect curve parameters.RESULTS:Individual Lingzhi,Kushen and Gancao extracts and ASHMI (the combination of individual extracts) inhibited production of interleukin (IL)-4 and IL-5 by murine memory Th2 cells and eotaxin-1 production by HLF-1 cells.The mean 25%-inhibitory-concentration (IC25)values (mg/mL)forASHMI,Lingzhi,Kushen and Gancaofor IL-4 production were 30.9,79.4,123,and 64.6,respectively; for IL-5 production were 30.2,263,123.2 and 100,respectively;for eotaxin-1 were 13.2,16.2,30.2,and 25.1,respectively.The IC50values (mg/mL) for ASHMI,Lingzhi,Kushen and Gancao for IL-4 production were 158.5,239.9,446.7,and 281.8,respectively; for eotaxin-1 were 38.1,33.1,100,and 158.5,respectively.The interaction indices of ASHMI constituents at IC25 were 0.35 for IL-4,0.21 for IL-5 and 0.59 for eotaxin-1.The interaction indices at IC50 values were 0.50 for IL-4 and 0.62 for eotaxin-1 inhibition.Inhibition of IL-5 did not reach IC50 values.All interaction indices were below 1 which indicated synergy.CONCLUSION:By comparing the interaction index values,we find that constituents in

  8. Submerged cultivation of Ganoderma lucidum and the effects of its polysaccharides on the production of human cytokines TNF-α, IL-12, IFN-γ, IL-2, IL-4, IL-10 and IL-17.

    Science.gov (United States)

    Habijanic, Jožica; Berovic, Marin; Boh, Bojana; Plankl, Mojca; Wraber, Branka

    2015-01-25

    An original strain of Ganoderma lucidum (W.Curt.:Fr.) Lloyd, MZKI G97 isolated from Slovenian habitats was grown by a submerged liquid substrate cultivation in a laboratory stirred tank reactor. Five fractions of extracellular and cell-wall polysaccharides were obtained by extraction, ethanol precipitation, and purification by ion-exchange, gel and affinity chromatography. The capacity of isolated polysaccharide fractions to induce innate inflammatory cytokines, and to modulate cytokine responses of activated lymphocytes was investigated. Human peripheral blood mononuclear cells (PBMC) were activated in vitro with polysaccharide fractions, in order to induce innate inflammatory cytokines: tumor necrosis factor alpha (TNF-α), interleukin (IL) 12 and interferon gamma (IFN-γ). For the immunomodulation capacity, polysaccharide fractions were cultured with ionomycine and phorbol myristate acetate (IONO+PMA) activated PBMC, and the concentrations of induced IL-2, IL-4, IFN-γ, IL-10 and IL-17 were measured. The results showed that polysaccharides from G. lucidum induced moderate to high amounts of innate inflammatory cytokines. Fungal cell-wall polysaccharides were stronger innate inflammatory cytokines inducers, while extracellular polysaccharides demonstrated a higher capacity to modulate cytokine responses of IONO+PMA induced production of IL-17. The results indicate that G. lucidum polysaccharides enhance Th1 response with high levels of IFN-γ and IL-2, and display low to no impact on IL-4 production. A similar pattern was observed at regulatory cytokine IL-10. All of the polysaccharide fractions tested induced IL-17 production at different concentration levels.

  9. Brain expression genome-wide association study (eGWAS identifies human disease-associated variants.

    Directory of Open Access Journals (Sweden)

    Fanggeng Zou

    Full Text Available Genetic variants that modify brain gene expression may also influence risk for human diseases. We measured expression levels of 24,526 transcripts in brain samples from the cerebellum and temporal cortex of autopsied subjects with Alzheimer's disease (AD, cerebellar n=197, temporal cortex n=202 and with other brain pathologies (non-AD, cerebellar n=177, temporal cortex n=197. We conducted an expression genome-wide association study (eGWAS using 213,528 cisSNPs within ± 100 kb of the tested transcripts. We identified 2,980 cerebellar cisSNP/transcript level associations (2,596 unique cisSNPs significant in both ADs and non-ADs (q<0.05, p=7.70 × 10(-5-1.67 × 10(-82. Of these, 2,089 were also significant in the temporal cortex (p=1.85 × 10(-5-1.70 × 10(-141. The top cerebellar cisSNPs had 2.4-fold enrichment for human disease-associated variants (p<10(-6. We identified novel cisSNP/transcript associations for human disease-associated variants, including progressive supranuclear palsy SLCO1A2/rs11568563, Parkinson's disease (PD MMRN1/rs6532197, Paget's disease OPTN/rs1561570; and we confirmed others, including PD MAPT/rs242557, systemic lupus erythematosus and ulcerative colitis IRF5/rs4728142, and type 1 diabetes mellitus RPS26/rs1701704. In our eGWAS, there was 2.9-3.3 fold enrichment (p<10(-6 of significant cisSNPs with suggestive AD-risk association (p<10(-3 in the Alzheimer's Disease Genetics Consortium GWAS. These results demonstrate the significant contributions of genetic factors to human brain gene expression, which are reliably detected across different brain regions and pathologies. The significant enrichment of brain cisSNPs among disease-associated variants advocates gene expression changes as a mechanism for many central nervous system (CNS and non-CNS diseases. Combined assessment of expression and disease GWAS may provide complementary information in discovery of human disease variants with functional implications. Our findings

  10. IL-4 alpha chain receptor (IL-4Rα polymorphisms in allergic bronchopulmonary sspergillosis

    Directory of Open Access Journals (Sweden)

    Consolino Judy D

    2006-02-01

    Full Text Available Abstract Background Allergic bronchopulmonary aspergillosis occurs in 7–10% of cystic fibrosis (CF and 1–2% of asthmatic patients. HLA-DR restriction and increased sensitivity to IL-4 stimulation have been proposed as risk factors in these populations. Objective We examined for the presence of IL-4 receptor alpha chain (IL-4Rα single nucleotide polymorphisms (SNPs in ABPA and whether these accounted for increased sensitivity to IL-4 stimulation. Methods One extracellular (ile75val and four cytoplasmic IL-4Rα SNPs were analyzed in 40 CF and 22 asthmatic patients and in 56 non-ABPA CF and asthmatic patients. Sensitivity to IL-4 stimulation was measured by induction of CD23 expression on B cells. Results IL-4Rα SNPs were observed in 95% of ABPA patients. The predominant IL-4Rα SNP was the extracellular IL-4Rα SNP, ile75val, observed in 80% of ABPA patients. Conclusion The presence of IL-4Rα SNPs, principally ile75val, appears to be a genetic risk for the development of ABPA.

  11. Peripheral inflammatory disease associated with centrally activated IL-1 system in humans and mice.

    Science.gov (United States)

    Lampa, Jon; Westman, Marie; Kadetoff, Diana; Agréus, Anna Nordenstedt; Le Maître, Erwan; Gillis-Haegerstrand, Caroline; Andersson, Magnus; Khademi, Mohsen; Corr, Maripat; Christianson, Christina A; Delaney, Ada; Yaksh, Tony L; Kosek, Eva; Svensson, Camilla I

    2012-07-31

    During peripheral immune activation caused by an infection or an inflammatory condition, the innate immune response signals to the brain and causes an up-regulation of central nervous system (CNS) cytokine production. Central actions of proinflammatory cytokines, in particular IL-1β, are pivotal for the induction of fever and fatigue. In the present study, the influence of peripheral chronic joint inflammatory disease in rheumatoid arthritis (RA) on CNS inflammation was investigated. Intrathecal interleukin (IL)-1β concentrations were markedly elevated in RA patients compared with controls or with patients with multiple sclerosis. Conversely, the anti-inflammatory IL-1 receptor antagonist and IL-4 were decreased in RA cerebrospinal fluid (CSF). Tumor necrosis factor and IL-6 levels in the CSF did not differ between patients and controls. Concerning IL-1β, CSF concentrations in RA patients were higher than in serum, indicating local production in the CNS, and there was a positive correlation between CSF IL-1β and fatigue assessments. Next, spinal inflammation in experimental arthritis was investigated. A marked increase of IL-1β, IL-18, and tumor necrosis factor, but not IL-6 mRNA production, in the spinal cord was observed, coinciding with increased arthritis scores in the KBxN serum transfer model. These data provide evidence that peripheral inflammation such as arthritis is associated with an immunological activation in the CNS in both humans and mice, suggesting a possible therapeutic target for centrally affecting conditions as fatigue in chronic inflammatory diseases, for which to date there are no specific treatments.

  12. Polymorphisms of IL-4, IL-4Rα, and AICDA Genes in Adult Allergic Asthma

    Institute of Scientific and Technical Information of China (English)

    崔天盆; 王琳; 吴健民; 胡丽华; 谢俊刚

    2003-01-01

    Summary: The relationship between 3 polymorphisms sites [interleulin-4 (IL-4), IL-4 receptor (IL-4R) α chain and activation-induced cytidine deaminase (AICDA)] and adult allergic asthma in Chinawas studied. By using case-control method, DNA and clinical data were obtained from allergic asth-matic patients and compared with those in the control subjects. The subjects were genotyped for theIL-4 C-589T promoter polymorphism, the IL-4R α chain Q576R and the AICDA C8408T by poly-merase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The resultsshowed that the IL-4 C-589T was not associated with adult allergic asthma in China. However, theIL-4R α chain 576R/R and AICDA 8408T/T frequency was significantly increased in allergic asthmagroup as compared with that in the control group [odd ratio (OR)= 3. 797 and 9. 127, respectively;P<0.01)] and was correlated with the increased plasma total IgE. These data suggested that theIL-4R α chain 576R/R and AICDA 8408T/T genotypes confer genetic susceptibility to adult allergicasthma in China.

  13. Mast cell production and response to IL-4 and IL-13.

    Science.gov (United States)

    McLeod, Jamie J A; Baker, Bianca; Ryan, John J

    2015-09-01

    IL-4 was identified as the first cytokine to be produced by mast cells and is responsible for promoting mast cell IL-13 production. IL-4 and IL-13 play a prominent role in stimulating and maintaining the allergic response. As closely related genes, IL-4 and IL-13 share a common receptor subunit, IL-4Rα, necessary for signaling. Here we summarize the literature on mast cell activation associated with IL-4 and IL-13 production, including downstream signaling. We also describe the positive and negative roles each cytokine plays in mast cell immunity and detail the differences that exist between mouse and human mast cell responses to IL-4 and IL-13.

  14. BCR ligation antagonizes the IL-21 enhancement of anti-CD40/IL-4 plasma cell differentiation and IgE production found in low density human B cell cultures.

    Science.gov (United States)

    Caven, Timothy H; Sturgill, Jamie L; Conrad, Daniel H

    2007-05-01

    We sought to discover the mechanisms explaining increased IgE production seen at low cell densities when IL-21 is added to human B cell cultures activated with anti-CD40 and IL-4. When cells were cultured in the absence of BCR ligation, qPCR demonstrated dramatic increases in mRNA for the plasma cell transcription factors BLIMP1 and XBP1. Furthermore, a majority of viable cells expressed high levels of CD38 while losing expression of surface IgD. In contrast, in the presence of BCR stimulation, both the XBP1 mRNA levels and CD38 cell surface expression were markedly reduced, and a large population of cells retained IgD expression, indicating reduced plasma cell differentiation. IgE levels were reduced in the BCR stimulated cultures by 90%, while IgG4 levels remained unchanged. In summary, IL-21 enhances IgE production at low densities through stimulating cell division and plasma cell differentiation and this activity is reduced upon BCR cross-linking.

  15. Association between IL-4 and IL-4R Polymorphisms and Periodontitis: A Meta-Analysis

    Science.gov (United States)

    Chen, Xue-Hong

    2017-01-01

    Background. Previous studies have revealed that gene polymorphisms of inflammatory factors may influence the development or progression of periodontitis, a main cause of tooth loss in adults; however, due to limitations of individual studies, inconsistent findings were reported. Objective. To meta-analytically investigate the relationship between periodontitis and the Interleukin-4 (IL-4) and Interleukin-4 receptor (IL-4R) gene polymorphisms. Methods. Databases were searched for relevant case-control studies. After study selection based on the predefined selection criteria, methodological quality assessment and data extraction were conducted independently by two reviewers, before subsequent statistical analyses. Results. 37 studies involving 4,385 patients and 5,168 controls were included. All the studied IL-4 polymorphisms were not significantly associated with periodontitis, except the -33C/T (CT versus CC: OR = 0.50, 95% CI = 0.28–0.88) associated with reduced AgP susceptibility. Positive association was found between IL-4R Q551 polymorphism and periodontitis susceptibility in three genetic models (R versus Q: OR = 1.59, 95% CI = 1.14–2.22; QR versus QQ: OR = 1.84, 95% CI = 1.21–2.80; RR + QR versus QQ: OR = 1.82, 95% CI = 1.22–2.72). Conclusions. A positive association exists between the IL-4R Q551R polymorphism and occurrence of CP. The IL-4 -33 CT genotype is negatively associated with the occurrence of AgP.

  16. SH-2-containing protein tyrosine phosphatase 1 is required for IL-4-induced IL-4R expression in spleen cells

    Institute of Scientific and Technical Information of China (English)

    CAO Xin; HUANG Zan; FAN Jingyi

    2005-01-01

    To investigate the role of SH-2-containing protein tyrosine phosphatase 1, SHP-1, in IL-4-induced IL-4 receptor (IL-4R) expression, we examined IL-4 receptor α-chain (IL-4Rα) mRNA expression in Na3VO4-treated wild type (WT) spleen cells and measured IL-4R mRNA in IL-4-stimulated spleen cells of viable motheaten mice (mev/mev). It is found that IL-4-induced IL-4R mRNA expression was impaired in Na3VO4-treated WT spleen cells and IL-4-stimulated mev/mev spleen cells. Here we show that the impaired IL-4-induced IL-4RαmRNA expression was due to reduced expression of IL-4R that led to impaired STAT6 signaling. We further demonstrate that reduction of IL-4Rαprotein expression in mev/mev spleen cells was due to alteration in cell compositions. In mev/mev spleen, the percentages of CD4+, CD8+, and CD19+ cells expressing relatively high levels of IL-4R were reduced dramatically while the percentages of Mac-1+ and Gr-1+ cells with relative low levels of IL-4R increased greatly. Despite the profound effect of reduced expression of IL-4R protein, the IL-4RαmRNA expression was comparable in spleen cells of littermate control mice (+/() and mev/mev mice and no differences were found in B cells, T cells, and macrophages, suggesting cell type-specific downregulation of IL-4R expression in macrophages through a posttranscriptional mechanism. Our study suggests that SHP-1 is required for IL-4-meidated function and indirectly regulates IL-4-meidated function in spleen cells by affecting hematopoiesis.

  17. Human Disease-Associated Genetic Variation Impacts Large Intergenic Non-Coding RNA Expression

    NARCIS (Netherlands)

    Kumar, Vinod; Westra, Harm-Jan; Karjalainen, Juha; Zhernakova, Daria V.; Esko, Tonu; Hrdlickova, Barbara; Almeida, Rodrigo; Zhernakova, Alexandra; Reinmaa, Eva; Hofker, Marten H.; Fehrmann, Rudolf S. N.; Fu, Jingyuan; Withoff, Sebo; Metspalu, Andres; Franke, Lude; Wijmenga, Cisca; Vosa, Urmo

    2013-01-01

    Recently it has become clear that only a small percentage (7%) of disease-associated single nucleotide polymorphisms (SNPs) are located in protein-coding regions, while the remaining 93% are located in gene regulatory regions or in intergenic regions. Thus, the understanding of how genetic variation

  18. IL-4、IL-13蛋白表达及抗IL-4、IL-13人源单链抗体的筛选%Expression of IL-4 and IL-13 proteins and selection of scFvs against IL-4 and IL-13

    Institute of Scientific and Technical Information of China (English)

    袁青; 黄黎; 郭夕源; 叶迎春; 年四季

    2013-01-01

    Objective:Expression of IL-4 and IL-13 proteins and selection of human scFvs against IL-4 and IL-13 by phage display.Methods:The mRNA of PBMC from healthy volunteer was extracted and cDNA of IL-4 and IL-13 were synthesized by RT-PCR,and the proteins of IL-4 and IL-13 were expressed and identified.The scFvs against IL-4 and IL-13 were selected from a non-immune human scFvs library by phage display with biotinylation IL-4 and IL-13 protein.Results:The size of cDNA of amplified IL-4 was 280 bp,and that of expressed fusion protein was about 27 kD.The size of cDNA of amplified IL-13 was 252 bp,and that of expressed fusion protein was about 25 kD.The human scFvs library was screened for three rounds by ribosome display,and about 37% scFvs has binding activities with IL-4 and about 27% scFvs has binding activities with IL-13.Four scFvs with good binding activities with IL-4 or IL-13 were selected and identified by Western blot.Conclusion:The scFvs against IL-4 and against IL-13 were selected successfully.%目的:表达IL-4和IL-13蛋白,从人源单链抗体文库中分别筛选抗IL-4和抗IL-13单链抗体.方法:采用RT-PCR从健康志愿者外周血单核细胞(PBMC) mRNA中扩增IL-4和IL-13 cDNA;构建硫氧还蛋白融合表达载体,转化大肠杆菌BL21,IPTG诱导表达并对表达产物进行纯化鉴定.以生物素化的IL-4和IL-13为抗原从前期构建的人源抗体文库中采用噬菌体展示技术分别筛选抗IL-4和抗IL-13人源单链抗体(scFv).结果:扩增的IL-4 cDNA大小为280 bp,表达的融合蛋白大小为27 kD左右.扩增的IL-13 cDNA大小为252 bp,表达的融合蛋白大小为25 kD左右.分别以生物素化的IL-4和IL-13蛋白为抗原,采用噬菌体展示技术对人源抗体文库进行3轮富集后,分别有大约37%的scFvs与IL-4有结合特性,有约27%的scFvs与IL-13有结合特性.筛选了4株分别与IL-4和IL-13结合能力强的单链抗体进行了Westem blot鉴定和测序.结论:成功筛选到抗IL-4

  19. IL-4 abrogates TH17 cell-mediated inflammation by selective silencing of IL-23 in antigen-presenting cells

    Science.gov (United States)

    Guenova, Emmanuella; Skabytska, Yuliya; Hoetzenecker, Wolfram; Weindl, Günther; Sauer, Karin; Tham, Manuela; Kim, Kyu-Won; Park, Ji-Hyeon; Seo, Ji Hae; Ignatova, Desislava; Cozzio, Antonio; Levesque, Mitchell P.; Volz, Thomas; Köberle, Martin; Kaesler, Susanne; Thomas, Peter; Mailhammer, Reinhard; Ghoreschi, Kamran; Schäkel, Knut; Amarov, Boyko; Eichner, Martin; Schaller, Martin; Clark, Rachael A.; Röcken, Martin; Biedermann, Tilo

    2015-01-01

    Interleukin 4 (IL-4) can suppress delayed-type hypersensitivity reactions (DTHRs), including organ-specific autoimmune diseases in mice and humans. Despite the broadly documented antiinflammatory effect of IL-4, the underlying mode of action remains incompletely understood, as IL-4 also promotes IL-12 production by dendritic cells (DCs) and IFN-γ–producing TH1 cells in vivo. Studying the impact of IL-4 on the polarization of human and mouse DCs, we found that IL-4 exerts opposing effects on the production of either IL-12 or IL-23. While promoting IL-12–producing capacity of DCs, IL-4 completely abrogates IL-23. Bone marrow chimeras proved that IL-4–mediated suppression of DTHRs relies on the signal transducer and activator of transcription 6 (STAT6)-dependent abrogation of IL-23 in antigen-presenting cells. Moreover, IL-4 therapy attenuated DTHRs by STAT6- and activating transcription factor 3 (ATF3)-dependent suppression of the IL-23/TH17 responses despite simultaneous enhancement of IL-12/TH1 responses. As IL-4 therapy also improves psoriasis in humans and suppresses IL-23/TH17 responses without blocking IL-12/TH1, selective IL-4–mediated IL-23/TH17 silencing is promising as treatment against harmful inflammation, while sparing the IL-12–dependent TH1 responses. PMID:25646481

  20. Detection of allergenic compounds using an IL-4/luciferase/CNS-1 transgenic mice model.

    Science.gov (United States)

    Bae, Chang Joon; Lee, Jae Won; Bae, Hee Sook; Shim, Sun Bo; Jee, Seung Wan; Lee, Su Hae; Lee, Chang Kyu; Hong, Jin Tae; Hwang, Dae Youn

    2011-04-01

    The interleukin-4 (IL-4) signaling cascade has been identified as a potentially important pathway in the development of allergies. The principal objective of this study was to produce novel transgenic (Tg) mice harboring the luciferase gene under the control of the human IL-4 promoter and the enhancer of IL-4 (CNS-1), in an effort to evaluate three types of allergens including a respiratory sensitizer, vaccine additives, and crude extracts of natural allergens in vivo. A new lineage of Tg mice was generated by the microinjection of pIL-4/Luc/CNS-1 constructs into a fertilized mice egg. The luciferase activity was successfully regulated by the IL-4 promoter in splenocytes cultured from IL-4/Luc/CNS-1 Tg mice. From the first five founder lines, one (#57) evidencing a profound response to ovalbumin was selected for use in evaluating the allergens. Additionally, the lungs, thymus, and lymph nodes of IL-4/Luc/CNS-1 Tg mice evidenced high luciferase activity in response to allergens such as phthalic anhydride (PA), trimellitic anhydride, ovalbumin, gelatin, Dermatophagoides pteronyssinus extracts, and Japanese cedar pollen, whereas key allergy-related indicators including ear thickness, Immunoglobulin E concentration, and the infiltration of inflammatory leukocytes in response to PA were unaltered in the Tg mice relative to the non-Tg mice. Furthermore, the expression levels of endogenous type 2 helper T cells cytokines and proinflammatory cytokines were similarly increased in these organs of IL-4/Luc/CNS-1 Tg mice in response to allergens. These results indicate that IL-4/Luc/CNS-1 Tg mice may be used as an animal model for the evaluation and prediction of the human body response to a variety of allergens originating from the environment and from certain industrial products.

  1. Recombinant human growth-regulated oncogene-alpha induces T lymphocyte chemotaxis. A process regulated via IL-8 receptors by IFN-gamma, TNF-alpha, IL-4, IL-10, and IL-13

    DEFF Research Database (Denmark)

    Jinquan, T; Frydenberg, Jane; Mukaida, N

    1995-01-01

    receptors on the cells. This process can be augmented by IFN-gamma and TNF-alpha, and inhibited by IL-4, IL-10, and IL-13. In addition, we also document that on T lymphocytes there exist IL-8 receptors that can be up-regulated by IFN-gamma, TNF-alpha, and IL-2. Our results demonstrate that rhGRO-alpha gene...

  2. An atopy-associated polymorphism in the ectodomain of the IL-4R(alpha) chain (V50) regulates the persistence of STAT6 phosphorylation.

    Science.gov (United States)

    Ford, Andrew Q; Heller, Nicola M; Stephenson, Linda; Boothby, Mark R; Keegan, Achsah D

    2009-08-01

    Several commonly occurring polymorphisms in the IL-4R(alpha) have been associated with atopy in humans; the Q576R and the S503P polymorphisms reside in the cytoplasmic domain, whereas the I50 to V50 polymorphism resides in the extracellular domain of the IL-4R(alpha). The effects of these polymorphisms on signaling remain controversial. To determine the effect of the polymorphisms on IL-4 signaling in human cells, we stably transfected the human monocytic cell line U937 with murine IL-4R(alpha) cDNA bearing the I or V at position 50 and the P503/R576 double mutant. Each form of the murine IL-4R(alpha) mediated tyrosine phosphorylation of STAT6 in response to murine IL-4 treatment similar to the induction of tyrosine phosphorylation by human IL-4 signaling through the endogenous human IL-4R(alpha). After IL-4 removal, tyrosine-phosphorylated STAT6 rapidly decayed in cells expressing I50 or P503R576 murine IL-4Ralpha. In contrast, STAT6 remained significantly phosphorylated for several hours after murine IL-4 withdrawal in cells expressing the V50 polymorphism. This persistence in tyrosine-phosphorylated STAT6 was associated with persistence in CIS mRNA expression. Blocking IL-4 signaling during the decay phase using the JAK inhibitor AG490 or the anti-IL-4R(alpha) Ab M1 abrogated the persistence of phosphorylated STAT6 observed in the V50-IL-4R(alpha)-expressing cells. These results indicate that the V50 polymorphism promotes sustained STAT6 phosphorylation and that this process is mediated by continued engagement of IL-4R(alpha), suggesting enhanced responses of V50 IL-4R when IL-4 is limiting.

  3. 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.

  4. Human gut dendritic cells drive aberrant gut-specific t-cell responses in ulcerative colitis, characterized by increased IL-4 production and loss of IL-22 and IFNγ.

    Science.gov (United States)

    Mann, Elizabeth R; Bernardo, David; Ng, Siew C; Rigby, Rachael J; Al-Hassi, Hafid O; Landy, Jon; Peake, Simon T C; Spranger, Henning; English, Nicholas R; Thomas, Linda V; Stagg, Andrew J; Knight, Stella C; Hart, Ailsa L

    2014-12-01

    : The pathogenesis of inflammatory bowel disease is incompletely understood but results from a dysregulated intestinal immune response to the luminal microbiota. CD4 T cells mediate tissue injury in the inflammatory bowel disease-associated immune response. Dendritic cells (DC) generate primary T-cell responses and mediate intestinal immune tolerance to prevent overt inflammation in response to the gut microbiota. However, most information regarding function of intestinal DC has come from mouse models, and information in humans is scarce. We show here that intestinal DC subsets are skewed in ulcerative colitis (UC) in humans, with a loss of CD103 lymph-node homing DC; this intestinal DC subset preferentially generates regulatory T cells in mice. We show infiltrates of DC negative for myeloid marker CD11c, with enhanced expression of Toll-like receptors for bacterial recognition. After mixed leukocyte reaction, DC from the inflamed UC colon had an enhanced ability to generate gut-specific CD4 T cells with enhanced production of interleukin-4 but a loss of interferon γ and interleukin-22 production. Conditioning intestinal DC with probiotic strain Lactobacillus casei Shirota in UC partially restored their normal function indicated by reduced Toll-like receptor 2/4 expression and restoration of their ability to imprint homing molecules on T cells and to generate interleukin-22 production by stimulated T cells. This study suggests that T-cell dysfunction in UC is driven by DC. T-cell responses can be manipulated indirectly through effects of bacterial conditioning on gut DC with implications for immunomodulatory effects of the commensal microbiota in vivo. Manipulation of DC to allow generation of DC-specific therapy may be beneficial in inflammatory bowel disease.

  5. Strategies targeting the IL-4/IL-13 axes in disease.

    Science.gov (United States)

    May, Richard D; Fung, Michael

    2015-09-01

    IL-4 and IL-13 are pleiotropic Th2 cytokines produced by a wide variety of different cell types and responsible for a broad range of biology and functions. Physiologically, Th2 cytokines are known to mediate host defense against parasites but they can also trigger disease if their activities are dysregulated. In this review we discuss the rationale for targeting the IL-4/IL-13 axes in asthma, atopic dermatitis, allergic rhinitis, COPD, cancer, inflammatory bowel disease, autoimmune disease and fibrotic disease as well as evaluating the associated clinical data derived from blocking IL-4, IL-13 or IL-4 and IL-13 together.

  6. Commentary: IL-4 and IL-13 receptors and signaling.

    Science.gov (United States)

    McCormick, Sarah M; Heller, Nicola M

    2015-09-01

    Interleukin (IL)-4 and IL-13 were discovered approximately 30years ago and were immediately linked to allergy and atopic diseases. Since then, new roles for IL-4 and IL-13 and their receptors in normal gestation, fetal development and neurological function and in the pathogenesis of cancer and fibrosis have been appreciated. Studying IL-4/-13 and their receptors has revealed important clues about cytokine biology and led to the development of numerous experimental therapeutics. Here we aim to highlight new discoveries and consolidate concepts in the field of IL-4 and IL-13 structure, receptor regulation, signaling and experimental therapeutics.

  7. Essential role of Stat6 in IL-4 signalling.

    Science.gov (United States)

    Takeda, K; Tanaka, T; Shi, W; Matsumoto, M; Minami, M; Kashiwamura, S; Nakanishi, K; Yoshida, N; Kishimoto, T; Akira, S

    1996-04-18

    Interleukin-4 (IL-4) is a pleiotropic lymphokine which plays an important role in the immune system. IL-4 activates two distinct signalling pathways through tyrosine phosphorylation of Stat6, a signal transducer and activator of transcription, and of a 170K protein called 4PS. To investigate the functional role of Stat6 in IL-4 signalling, we generated mice deficient in Stat6 by gene targeting. We report here that in the mutant mice, expression of CD23 and major histocompatibility complex (MHC) class II in resting B cells was not enhanced in response to IL-4. IL-4 induced B-cell proliferation costimulated by anti-IgM antibody was abolished. The T-cell proliferative response was also notably reduced. Furthermore, production of Th2 cytokines from T cells as well as IgE and IgG1 responses after nematode infection were profoundly reduced. These findings agreed with those obtained in IL-4 deficient mice or using antibodies to IL-4 and the IL-4 receptor. We conclude that Stat6 plays a central role in exerting IL-4 mediated biological responses.

  8. HUMAN MIGRATION, DIVERSITY AND DISEASE ASSOCIATION: A CONVERGENT ROLE OF ESTABLISHED AND EMERGING DNA MARKERS

    Directory of Open Access Journals (Sweden)

    Pohhraj eGuha

    2013-08-01

    Full Text Available With the gradual development of intelligence, human got curious to know his origin and evolutionary background. Historical statements and anthropological findings were his primary tool for solving the puzzles of his own origin, until came the golden era of molecular markers which took no time to prove it’s excellence in unveiling answers to the questions regarding the migration pattern of human across different geographical regions. As a bonus these markers proved very much beneficial in solving criminal offences and in understanding the etiology of many dreaded diseases and to design their prevention. In this review, we have aimed to throw light on some of the promising molecular markers which are very much in application now-a-days for not only understanding the evolutionary background and ancient migratory routes of humans but also in the field of forensics and human health.

  9. IL-4 and IL-4 receptor expression is dispensable for the development and function of natural killer T cells.

    Directory of Open Access Journals (Sweden)

    Archna Sharma

    Full Text Available CD4 T cells acquire functional properties including cytokine production upon antigenic stimulation through the T cell receptor (TCR and differentiate into T helper (Th cells. Th1 cells produce interferon (IFN-γ and Th2 cells produce interleukin (IL-4. Th1 and 2 cells utilize IFN-γ and IL-4 for further maturation and maintenance, respectively. Promyelocytic leukemia zinc finger (PLZF-expressing invariant natural killer T (iNKT cells develop in the thymus and acquire functional ability to produce IL-4 and IFN-γ in the thymus in the absence of antigenic stimulation. In response to antigenic stimulation, iNKT cells rapidly produce IFN-γ and IL-4. However, it is still unknown as to whether iNKT cells require these cytokines for maturation or survival in vivo. In this study, using IL-4- and IL-4 receptor- (IL-4R deficient mice, we demonstrate that IL-4 as well as IL-4R expression is dispensable for the development, function and maintenance of iNKT cells.

  10. Genetic analysis of completely sequenced disease-associated MHC haplotypes identifies shuffling of segments in recent human history.

    Directory of Open Access Journals (Sweden)

    James A Traherne

    2006-01-01

    Full Text Available The major histocompatibility complex (MHC is recognised as one of the most important genetic regions in relation to common human disease. Advancement in identification of MHC genes that confer susceptibility to disease requires greater knowledge of sequence variation across the complex. Highly duplicated and polymorphic regions of the human genome such as the MHC are, however, somewhat refractory to some whole-genome analysis methods. To address this issue, we are employing a bacterial artificial chromosome (BAC cloning strategy to sequence entire MHC haplotypes from consanguineous cell lines as part of the MHC Haplotype Project. Here we present 4.25 Mb of the human haplotype QBL (HLA-A26-B18-Cw5-DR3-DQ2 and compare it with the MHC reference haplotype and with a second haplotype, COX (HLA-A1-B8-Cw7-DR3-DQ2, that shares the same HLA-DRB1, -DQA1, and -DQB1 alleles. We have defined the complete gene, splice variant, and sequence variation contents of all three haplotypes, comprising over 259 annotated loci and over 20,000 single nucleotide polymorphisms (SNPs. Certain coding sequences vary significantly between different haplotypes, making them candidates for functional and disease-association studies. Analysis of the two DR3 haplotypes allowed delineation of the shared sequence between two HLA class II-related haplotypes differing in disease associations and the identification of at least one of the sites that mediated the original recombination event. The levels of variation across the MHC were similar to those seen for other HLA-disparate haplotypes, except for a 158-kb segment that contained the HLA-DRB1, -DQA1, and -DQB1 genes and showed very limited polymorphism compatible with identity-by-descent and relatively recent common ancestry (<3,400 generations. These results indicate that the differential disease associations of these two DR3 haplotypes are due to sequence variation outside this central 158-kb segment, and that shuffling of

  11. The impact of metabolic disease associated with metabolic syndrome on human pregnancy.

    Science.gov (United States)

    Malek, Antoine

    2014-01-01

    Metabolic diseases induced by metabolic syndrome (MS) have been increased during the past two decades. During healthy pregnancy maternal organs and placenta are challenged to adapt to the increasingly physiological changes. In addition to the increasingly proatherogenic MS, pregnant woman develops a high cardiac output, hypercoagulability, increased inflammatory activity and insulin resistance with dyslipidemia. The MS describes a cluster of metabolic changes associated with an impact on the physiology of many organs. While the metabolic syndrome is directly responsible for the development of atherosclerotic cardiovascular disease, additional impact on human pregnancy like preterm delivery with low-birth-weight infants as well as the development of diseases such as diabetes, preeclampsia and hypertension. Recent evidence suggests that MS is originated in fetal life in association with maternal nutrition during pregnancy and fetal programming which apparently increases the susceptibility for MS in children and later life. This review will describe the MS in association with the origin of the emerging diseases during pregnancy such as diabetes, preeclampsia and others. The influence of perinatal environment and maternal diet and smoking on MS as well as the genetic biomarkers of MS will be described.

  12. Mass Cytometry of the Human Mucosal Immune System Identifies Tissue- and Disease-Associated Immune Subsets.

    Science.gov (United States)

    van Unen, Vincent; Li, Na; Molendijk, Ilse; Temurhan, Mine; Höllt, Thomas; van der Meulen-de Jong, Andrea E; Verspaget, Hein W; Mearin, M Luisa; Mulder, Chris J; van Bergen, Jeroen; Lelieveldt, Boudewijn P F; Koning, Frits

    2016-05-17

    Inflammatory intestinal diseases are characterized by abnormal immune responses and affect distinct locations of the gastrointestinal tract. Although the role of several immune subsets in driving intestinal pathology has been studied, a system-wide approach that simultaneously interrogates all major lineages on a single-cell basis is lacking. We used high-dimensional mass cytometry to generate a system-wide view of the human mucosal immune system in health and disease. We distinguished 142 immune subsets and through computational applications found distinct immune subsets in peripheral blood mononuclear cells and intestinal biopsies that distinguished patients from controls. In addition, mucosal lymphoid malignancies were readily detected as well as precursors from which these likely derived. These findings indicate that an integrated high-dimensional analysis of the entire immune system can identify immune subsets associated with the pathogenesis of complex intestinal disorders. This might have implications for diagnostic procedures, immune-monitoring, and treatment of intestinal diseases and mucosal malignancies.

  13. Resistance to Recombinant Human Erythropoietin Therapy in a Rat Model of Chronic Kidney Disease Associated Anemia.

    Science.gov (United States)

    Garrido, Patrícia; Ribeiro, Sandra; Fernandes, João; Vala, Helena; Rocha-Pereira, Petronila; Bronze-da-Rocha, Elsa; Belo, Luís; Costa, Elísio; Santos-Silva, Alice; Reis, Flávio

    2015-12-25

    This study aimed to elucidate the mechanisms explaining the persistence of anemia and resistance to recombinant human erythropoietin (rHuEPO) therapy in a rat model of chronic kidney disease (CKD)-associated anemia with formation of anti-rHuEPO antibodies. The remnant kidney rat model of CKD induced by 5/6 nephrectomy was used to test a long-term (nine weeks) high dose of rHuEPO (200 UI/kg bw/week) treatment. Hematological and biochemical parameters were evaluated as well as serum and tissue (kidney, liver and/or duodenum) protein and/or gene expression of mediators of erythropoiesis, iron metabolism and tissue hypoxia, inflammation, and fibrosis. Long-term treatment with a high rHuEPO dose is associated with development of resistance to therapy as a result of antibodies formation. In this condition, serum EPO levels are not deficient and iron availability is recovered by increased duodenal absorption. However, erythropoiesis is not stimulated, and the resistance to endogenous EPO effect and to rHuEPO therapy results from the development of a hypoxic, inflammatory and fibrotic milieu in the kidney tissue. This study provides new insights that could be important to ameliorate the current therapeutic strategies used to treat patients with CKD-associated anemia, in particular those that become resistant to rHuEPO therapy.

  14. Bone diseases associated with human immunodeficiency virus infection: pathogenesis, risk factors and clinical management.

    Science.gov (United States)

    Bongiovanni, Marco; Tincati, Camilla

    2006-06-01

    Bone disorders such as osteopenia and osteoporosis have been recently reported in patients infected with the human immunodeficiency virus (HIV), but their etiology remains still unknown. The prevalence estimates vary widely among the different studies and can be affected by concomitant factors such as the overlapping of other possible conditions inducing bone loss as lypodystrophy, advanced HIV-disease, advanced age, low body weight or concomitant use of other drugs. All the reports at the moment available in the literature showed a higher than expected prevalence of reduced bone mineral density (BMD) in HIV-infected subjects both naïve and receiving potent antiretroviral therapy compared to healthy controls. This controversial can suggest a double role played by both antiretroviral drugs and HIV itself due to immune activation and/or cytokines disregulation. An improved understanding of the pathogenesis of bone disorders can result in better preventative and therapeutic measures. However, the clinical relevance and the risk of fractures remains undefined in HIV-population. The clinical management of osteopenia and osteoporosis in HIV-infected subjects is still being evaluated. Addressing potential underlying bone disease risk factors (e.g., smoking and alcohol intake, use of corticosteroids, advanced age, low body weight), evaluating calcium and vitamin D intake, and performing dual x-ray absorptiometry in HIV-infected individuals who have risk factors for bone disease can be important strategies to prevent osteopenia and osteoporosis in this population. The administration of bisphosphonates (e.g., alendronate), with calcium and vitamin D supplementation, may be a reasonable and effective option to treat osteoporosis in these subjects.

  15. Orthologs of Human Disease Associated Genes and RNAi Analysis of Silencing Insulin Receptor Gene in Bombyx mori

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    Zan Zhang

    2014-10-01

    Full Text Available The silkworm, Bombyx mori L., is an important economic insect that has been domesticated for thousands of years to produce silk. It is our great interest to investigate the possibility of developing the B. mori as human disease model. We searched the orthologs of human disease associated genes in the B. mori by bi-directional best hits of BLAST and confirmed by searching the OrthoDB. In total, 5006 genes corresponding to 1612 kinds of human diseases had orthologs in the B. mori, among which, there are 25 genes associated with diabetes mellitus. Of these, we selected the insulin receptor gene of the B. mori (Bm-INSR to study its expression in different tissues and at different developmental stages and tissues. Quantitative PCR showed that Bm-INSR was highly expressed in the Malpighian tubules but expressed at low levels in the testis. It was highly expressed in the 3rd and 4th instar larvae, and adult. We knocked down Bm-INSR expression using RNA interference. The abundance of Bm-INSR transcripts were dramatically reduced to ~4% of the control level at 6 days after dsRNA injection and the RNAi-treated B. mori individuals showed apparent growth inhibition and malformation such as abnormal body color in black, which is the typical symptom of diabetic patients. Our results demonstrate that B. mori has potential use as an animal model for diabetic mellitus research.

  16. IL-4 and IL-13 signaling in allergic airway disease.

    Science.gov (United States)

    Gour, Naina; Wills-Karp, Marsha

    2015-09-01

    Aberrant production of the prototypical type 2 cytokines, interleukin (IL)-4 and IL-13 has long been associated with the pathogenesis of allergic disorders. Despite tremendous scientific inquiry, the similarities in their structure, and receptor usage have made it difficult to ascertain the distinct role that these two look-alike cytokines play in the onset and perpetuation of allergic inflammation. However, recent discoveries of differences in receptor distribution, utilization/assembly and affinity between IL-4 and IL-13, along with the discovery of unique innate lymphoid 2 cells (ILC2) which preferentially produce IL-13, not IL-4, are beginning to shed light on these mysteries. The purpose of this chapter is to review our current understanding of the distinct roles that IL-4 and IL-13 play in allergic inflammatory states and the utility of their modulation as potential therapeutic strategies for the treatment of allergic disorders.

  17. Association between interleukin-4 (IL-4), gene polymorphisms (C ...

    African Journals Online (AJOL)

    Nourollah Ramroodi

    2016-06-10

    Jun 10, 2016 ... The study was approved by the ethics in medical research com- mittee at Zahedan .... 220 bp. IL-4 gene important polymorphisms in Iranian migraineurs. 31 ..... DA, et al. Genetic and environmental influences on migraine: a.

  18. Experimental neurocysticercosis: absence of IL-4 induces lower encephalitis

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    Hidelberto Matos Silva

    Full Text Available ABSTRACT Neurocysticercosis (NCC is the most severe clinical manifestation of cysticercosis. One of the factors responsible for its symptomatology is the host inflammatory response. Therefore the influence of interleukin 4 (IL-4 on the induction of encephalitis in experimental NCC was evaluated. Methods BALB/c (WT and BALB/c (IL-4-KO mice were inoculated intracranially with Taenia crassiceps cysticerci and euthanized at 7, 30, 60 and 90 days later, the encephala removed and histopathologically analyzed. Results The absence of IL-4 induced greater parasitism. In the initial phase of the infection, IL-4-KO showed a lower intensity in the inflammatory infiltration of polimorphonuclear cells in the host-parasite interface and intra-parenquimatous edema. The IL-4-KO animals, in the late phase of the infection, showed lower intensity of ventriculomegaly, encephalitis, and meningitis, and greater survival of the parasites in comparison with the WT animals. Conclusion The absence of IL-4 induced lower inflammatory infiltration, ventriculomegaly and perivasculitis in experimental NCC.

  19. Construction and application of elastin like polypeptide containing IL-4 receptor targeting peptide.

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    Vijaya Sarangthem

    Full Text Available Various human solid tumors highly express IL-4 receptors which amplify the expression of some of anti-apoptotic proteins, preventing drug-induced cancer cell death. Thus, IL-4 receptor targeted drug delivery can possibly increase the therapeutic efficacy in cancer treatment. Macromolecular carriers with multivalent targeting moieties offered great advantages in cancer therapy as they not only increase the plasma half-life of the drug but also allow delivery of therapeutic drugs to the cancer cells with higher specificity, minimizing the deleterious effects of the drug on normal cells. In this study we designed a library of elastin like polypeptide (ELP polymers containing tumor targeting AP1 peptide using recursive directional ligation method. AP1 was previously discovered as an atherosclerotic plaque and breast tumor tissue homing peptide using phage display screening method, and it can selectively bind to the interleukin 4 receptor (IL-4R. The fluorescently labeled [AP1-V12]6, an ELP polymer containing six AP1 enhanced tumor-specific targeting ability and uptake efficiency in H226 and MDA-MB-231 cancer cell lines in vitro. Surface plasmon resonance analysis showed that multivalent presentation of the targeting ligand in the ELP polymer increased the binding affinity towards IL-4 receptor compared to free peptide. The binding of [AP1-V12]6 to cancer cells was remarkably reduced when IL-4 receptors were blocked by antibody against IL-4 receptor further confirmed its binding. Importantly, the Cy5.5-labeled [AP1-V12]6 demonstrated excellent homing and longer retention in tumor tissues in MDA-MB-231 xenograft mouse model. Immunohistological studies of tumor tissues further validated the targeting efficiency of [AP1-V12]6 to tumor tissue. These results indicate that designed [AP1-V12]6 can serve as a novel carrier for selective delivery of therapeutic drugs to tumors.

  20. Expression profiles of muscle disease-associated genes and their isoforms during differentiation of cultured human skeletal muscle cells

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    Abdul-Hussein Saba

    2012-12-01

    Full Text Available Abstract Background The formation of contractile myofibrils requires the stepwise onset of expression of muscle specific proteins. It is likely that elucidation of the expression patterns of muscle-specific sarcomeric proteins is important to understand muscle disorders originating from defects in contractile sarcomeric proteins. Methods We investigated the expression profile of a panel of sarcomeric components with a focus on proteins associated with a group of congenital disorders. The analyses were performed in cultured human skeletal muscle cells during myoblast proliferation and myotube development. Results Our culture technique resulted in the development of striated myotubes and the expression of adult isoforms of the sarcomeric proteins, such as fast TnI, fast TnT, adult fast and slow MyHC isoforms and predominantly skeletal muscle rather than cardiac actin. Many proteins involved in muscle diseases, such as beta tropomyosin, slow TnI, slow MyBPC and cardiac TnI were readily detected in the initial stages of muscle cell differentiation, suggesting the possibility of an early role for these proteins as constituent of the developing contractile apparatus during myofibrillogenesis. This suggests that in disease conditions the mechanisms of pathogenesis for each of the mutated sarcomeric proteins might be reflected by altered expression patterns, and disturbed assembly of cytoskeletal, myofibrillar structures and muscle development. Conclusions In conclusion, we here confirm that cell cultures of human skeletal muscle are an appropriate tool to study developmental stages of myofibrillogenesis. The expression of several disease-associated proteins indicates that they might be a useful model system for studying the pathogenesis of muscle diseases caused by defects in specific sarcomeric constituents.

  1. LincSNP 2.0: an updated database for linking disease-associated SNPs to human long non-coding RNAs and their TFBSs

    Science.gov (United States)

    Ning, Shangwei; Yue, Ming; Wang, Peng; Liu, Yue; Zhi, Hui; Zhang, Yan; Zhang, Jizhou; Gao, Yue; Guo, Maoni; Zhou, Dianshuang; Li, Xin; Li, Xia

    2017-01-01

    We describe LincSNP 2.0 (http://bioinfo.hrbmu.edu.cn/LincSNP), an updated database that is used specifically to store and annotate disease-associated single nucleotide polymorphisms (SNPs) in human long non-coding RNAs (lncRNAs) and their transcription factor binding sites (TFBSs). In LincSNP 2.0, we have updated the database with more data and several new features, including (i) expanding disease-associated SNPs in human lncRNAs; (ii) identifying disease-associated SNPs in lncRNA TFBSs; (iii) updating LD-SNPs from the 1000 Genomes Project; and (iv) collecting more experimentally supported SNP-lncRNA-disease associations. Furthermore, we developed three flexible online tools to retrieve and analyze the data. Linc-Mart is a convenient way for users to customize their own data. Linc-Browse is a tool for all data visualization. Linc-Score predicts the associations between lncRNA and disease. In addition, we provided users a newly designed, user-friendly interface to search and download all the data in LincSNP 2.0 and we also provided an interface to submit novel data into the database. LincSNP 2.0 is a continually updated database and will serve as an important resource for investigating the functions and mechanisms of lncRNAs in human diseases. PMID:27924020

  2. 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.

  3. A path-based measurement for human miRNA functional similarities using miRNA-disease associations

    Science.gov (United States)

    Ding, Pingjian; Luo, Jiawei; Xiao, Qiu; Chen, Xiangtao

    2016-09-01

    Compared with the sequence and expression similarity, miRNA functional similarity is so important for biology researches and many applications such as miRNA clustering, miRNA function prediction, miRNA synergism identification and disease miRNA prioritization. However, the existing methods always utilized the predicted miRNA target which has high false positive and false negative to calculate the miRNA functional similarity. Meanwhile, it is difficult to achieve high reliability of miRNA functional similarity with miRNA-disease associations. Therefore, it is increasingly needed to improve the measurement of miRNA functional similarity. In this study, we develop a novel path-based calculation method of miRNA functional similarity based on miRNA-disease associations, called MFSP. Compared with other methods, our method obtains higher average functional similarity of intra-family and intra-cluster selected groups. Meanwhile, the lower average functional similarity of inter-family and inter-cluster miRNA pair is obtained. In addition, the smaller p-value is achieved, while applying Wilcoxon rank-sum test and Kruskal-Wallis test to different miRNA groups. The relationship between miRNA functional similarity and other information sources is exhibited. Furthermore, the constructed miRNA functional network based on MFSP is a scale-free and small-world network. Moreover, the higher AUC for miRNA-disease prediction indicates the ability of MFSP uncovering miRNA functional similarity.

  4. IL-4 induces the formation of multinucleated giant cells and expression of β5 integrin in central giant cell lesion

    Science.gov (United States)

    Aghbali, Amirala; Rafieyan, Sona; Mohamed-Khosroshahi, Leila; Baradaran, Behzad; Shanehbandi, Dariush

    2017-01-01

    Background It is now well established that IL-4 has a central role in the development of monocytes to multinucleated giant cells (MGCs) by inducing the expression of integrins on the surface of monocytes. The aim of this study was to investigate the potential role of IL-4 in induction of β5 integrin expression in the peripheral blood samples of patients with giant cell granuloma. Material and Methods Monocytes were isolated from peripheral blood samples of patients with central giant cell granuloma (CGCG) and healthy controls using human Monocyte Isolation Kit II. Isolated monocytes were then cultured in the absence or presence of IL-4 (10 and 20 ng/mL), and following RNA extraction and cDNA synthesis, Real-time PCR was performed to determine the level of β5 integrin expression. The formation of CGCGs and morphological analyses were done under light microscopy. For confirmation of CGCGs, immunocytochemistry technique was also carried out by anti-RANK (receptor-activator of NF-κB ligand) antibody. Results In both patient and control groups, β5 levels were significantly enhanced by increasing the IL-4 dose from 10 to 20 ng/mL. In addition, these differences were significant between patient and control groups without IL-4 treatment. On the other hand, the number of cells which expressed RANK and therefore the number of giant cells were significantly higher in the patient group in comparison to controls, as assessed by immunohistochemistry evaluations. Conclusions In this study, we showed an elevation in the expression levels of β5 integrin when stimulated by IL-4. It is strongly indicated that this integrin acts as an important mediator during macrophage to macrophage fusion and development of giant cells. Key words:β5 integrin, giant cell, Il-4, monocyte, rank. PMID:27918730

  5. Investigation of the therapeutic efficacy of codelivery of psiRNA-vascular endothelial growth factor and pIL-4 into chitosan nanoparticles in the breast tumor model.

    Science.gov (United States)

    Şalva, Emine; Turan, Suna O; Kabasakal, Levent; Alan, Saadet; Özkan, Naziye; Eren, Fatih; Akbuğa, Jülide

    2014-03-01

    Angiogenesis has been known to increase tumor growth and for its metastatic potential in human tumors. Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis and is a promising therapeutic target for breast cancer. VEGF is an essential target for RNAi-based gene therapy of breast cancer. Interleukin-4 (IL-4) may act as an anti-angiogenic molecule that inhibits tumor growth and migration in rats. The purpose of the present study was to improve therapeutic efficacy in breast cancer with the codelivery of siRNA-expressing plasmid targeting VEGF and IL-4-expressing plasmid encapsulating into chitosan nanoparticles (NPs). The codelivery of psiVEGF and pIL-4 plasmids greatly enhanced in vitro and in vivo gene-silencing efficiency. For the in vitro study, when psiVEGF and pIL-4 into chitosan NPs were combined (81%), the gene-silencing effect was higher than psiVEGF and pIL-4 NPs alone. The in vivo study breast tumor model demonstrated that the administration of coencapsulation of psiVEGF and pIL-4 into chitosan NPs caused an additive effect on breast tumor growth inhibition (97%), compared with containing NPs psiVEGF or pIL-4 alone. These results indicate that chitosan NPs can be effectively used for the codelivery of pIL-4 and siVEGF-expressing plasmid in a combination therapy against breast cancer.

  6. IL-4 Downregulates IL-1β and IL-6 and Induces GATA3 in Psoriatic Epidermal Cells: Route of Action of a Th2 Cytokine.

    Science.gov (United States)

    Onderdijk, Armanda J; Baerveldt, Ewout M; Kurek, Dorota; Kant, Marius; Florencia, Edwin F; Debets, Reno; Prens, Errol P

    2015-08-15

    Clinical improvement of psoriasis induced by IL-4 treatment has been ascribed to changes in dermal inflammatory cells, such as activation of Th2 cells and tolerization of dendritic cells by suppressing IL-23 production. The pathologic epidermal alterations in psoriatic lesional skin include increased epidermal expression of IL-1β, IL-6, S100A7, and human β-defensin 2 (hBD2) and a downregulated expression of the epidermal transcription factor GATA3. Effects of IL-4 on the epidermal compartment of psoriasis lesions were not previously investigated. Therefore, we investigated whether IL-4 directly affects abovementioned psoriatic markers in the epidermal compartment. We cultured freshly isolated psoriatic epidermal cells, whole psoriatic and healthy skin biopsies, human keratinocytes and Langerhans cells with IL-4. The secretion of IL-1β and IL-6 by psoriatic epidermal cells was inhibited by IL-4 via transcriptional and posttranscriptional mechanisms, respectively. In normal skin, IL-4 inhibited IL-1β- and IL-17A-induced hBD2 expression in vitro. In addition, IL-4 reduced the protein expression of hBD2 in psoriatic skin biopsies and induced phospho-STAT6 protein. Epidermal GATA3 mRNA and protein were significantly upregulated by IL-4 in epidermal cells and keratinocytes. Our data argue that IL-4 improves psoriasis not only via modification/induction of Th2 cells and type II dendritic cells, but also via direct inhibition of inflammatory cytokines in resident IL-4R-expressing epidermal cells and thereby alters the psoriatic skin phenotype toward a healthy skin phenotype.

  7. American Behcet's Disease Association

    Science.gov (United States)

    ... Behcet's Awareness Day Behcet's Disease Awareness Share your story and educate others about Behcet's: www.rareconnect.org/en/community/behcet-s-syndrome Upcoming Events American Behcet's Disease Association PO BOX 80576 Rochester, MI ...

  8. IL-4 regulates susceptibility to intestinal inflammation in murine food allergy

    National Research Council Canada - National Science Library

    Cristina R. Cardoso; Pauline R. Provinciatto; Dannielle F. Godoi; Beatriz R. Ferreira; Gerlinde Teixeira; Marcos A. Rossi; Fernando Q. Cunha; João S. Silva

    2009-01-01

    ... observed in food allergy. Accordingly, this work aimed to study the role of Th2/IL-4-dependent responses in the development of food allergy and intestinal pathology. C57BL/6 wild-type (WT) and IL-4...

  9. Delayed allograft rejection in mice transgenic for a soluble form of the IL-4 receptor.

    Science.gov (United States)

    Maliszewski, C R; Morrissey, P J; Fanslow, W C; Sato, T A; Willis, C; Davison, B

    1992-09-01

    Accumulating evidence suggests that in serum and other biological fluids, cytokine binding is a property associated with soluble proteins, including a high-affinity soluble version of the IL-4 receptor (sIL-4R). While it is tempting to speculate that sIL-4R might act as a serum carrier protein or serve to inhibit or modulate IL-4 action, specific biological roles for sIL-4R remain to be established. To further assess the immunoregulatory and therapeutic potential of sIL-4R and other soluble receptors, we have created transgenic mice which constitutively express elevated levels of biologically active sIL-4R. Phenotypic characterization of lymphoid organs in sIL-4R transgenic mice revealed normal numbers of B and T cells and normal surface marker expression. Splenic lymphocytes displayed normal in vitro activities as measured by the PFC response and generation of cytotoxic T cells. In addition, antigen-specific IgE and IgG1 in vivo responses were similar in control and transgenic mice. Despite the apparent developmental normality of the sIL-4R transgenic mice, these animals were markedly deficient in the ability to reject cardiac allografts, suggesting that IL-4 is critical for the generation of alloreactivity. The results further suggest that the ability of sIL-4R to regulate IL-4 activities may be under the control of complex interactions that remain to be elucidated.

  10. Monocyte cell surface glycosaminoglycans positively modulate IL-4-induced differentiation toward dendritic cells.

    NARCIS (Netherlands)

    Dekker, E. den; Grefte, S.; Huijs, T.; Dam, G.B. ten; Versteeg, E.M.M.; Berk, L.C.J. van den; Bladergroen, B.A.; Kuppevelt, A.H.M.S.M. van; Figdor, C.G.; Torensma, R.

    2008-01-01

    IL-4 induces the differentiation of monocytes toward dendritic cells (DCs). The activity of many cytokines is modulated by glycosaminoglycans (GAGs). In this study, we explored the effect of GAGs on the IL-4-induced differentiation of monocytes toward DCs. IL-4 dose-dependently up-regulated the expr

  11. A preliminary study on the association of single nucleotide polymorphisms of interleukin 4 (IL4, IL13, IL4 receptor alpha (IL4Rα & Toll-like receptor 4 (TLR4 genes with asthma in Indian adults

    Directory of Open Access Journals (Sweden)

    Parisa Davoodi

    2015-01-01

    Full Text Available Background & objectives: Interleukin 4 (IL4 and IL13 genes are believed to be responsible for inflammation of the airways in asthmatics. These share a common receptor component called IL4Rα which is another potentially important candidate gene linked to asthma phenotypes. Another gene Toll-like receptor 4 (TLR4 might affect the incidence or progression of asthma through the expression of proinflammatory genes. Several single nucleotide polymorphisms (SNPs in IL4, IL13, IL4Rα and TLR4 have been reported to be linked to asthma or related phenotypes in several ethnic populations using linkage studies and association studies. However, the results have not been consistent. We investigated five SNPs (C-589T and C-33T of IL4, G+2044A of IL13, A+1902G of IL4Rα, and A+896G of TLR4 in patients with adult onset asthma to evaluate their role in manifestation and severity of asthma. Methods: Adult (>18 yr of age patients with asthma (n=100 and healthy controls (n=50 were included in the study. Genotyping was performed using sequenom MassARRAY technology. Results: The mutant alleles of the C-589T and C-33T SNPs in the promoter region of IL4 were present in 4 per cent patients with asthma but absent from the control group suggesting that the variations in IL4 may contribute to asthma occurrence. The SNPs of other genes were seen in both controls and patients. Interpretation & conclusions: The results suggest the possible association between the genetic distribution of C-589T and C-33T SNPs of IL4 with asthma in Indian adults.

  12. 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.

  13. The human endogenous retrovirus link between genes and environment in multiple sclerosis and in multifactorial diseases associating neuroinflammation.

    Science.gov (United States)

    Perron, Hervé; Lang, Alois

    2010-08-01

    Endogenous retroviruses represent about 8% of the human genome and belong to the superfamily of transposable and retrotransposable genetic elements. Altogether, these mobile genetic elements and their numerous inactivated "junk" sequences represent nearly one half of the human DNA. Nonetheless, a significant part of this "non-conventional" genome has retained potential activity. Epigenetic control is notably involved in silencing most of these genetic elements but certain environmental factors such as viruses are known to dysregulate their expression in susceptible cells. More particularly, embryonal cells with limited gene methylation are most susceptible to uncontrolled activation of these mobile genetic elements by, e.g., viral infections. In particular, certain viruses transactivate promoters from endogenous retroviral family type W (HERV-W). HERV-W RNA was first isolated in circulating viral particles (Multiple Sclerosis-associated RetroViral element, MSRV) that have been associated with the evolution and prognosis of multiple sclerosis. HERV-W elements encode a powerful immunopathogenic envelope protein (ENV) that activates a pro-inflammatory and autoimmune cascade through interaction with Toll-like receptor 4 on immune cells. This ENV protein has repeatedly been detected in MS brain lesions and may be involved in other diseases. Epigenetic factors controlling HERV-W ENV protein expression then reveal critical. This review addresses the gene-environment epigenetic interface of such HERV-W elements and its potential involvement in disease.

  14. Trypanosoma cruzi in Brazilian Amazonia: Lineages TCI and TCIIa in wild primates, Rhodnius spp. and in humans with Chagas disease associated with oral transmission.

    Science.gov (United States)

    Marcili, Arlei; Valente, Vera C; Valente, Sebastião A; Junqueira, Angela C V; da Silva, Flávia Maia; Pinto, Ana Yecê das Neves; Naiff, Roberto D; Campaner, Marta; Coura, José R; Camargo, Erney P; Miles, Michael A; Teixeira, Marta M G

    2009-04-01

    In this study, we provide phylogenetic and biogeographic evidence that the Trypanosoma cruzi lineages T. cruzi I (TCI) and T. cruzi IIa (TCIIa) circulate amongst non-human primates in Brazilian Amazonia, and are transmitted by Rhodnius species in overlapping arboreal transmission cycles, sporadically infecting humans. TCI presented higher prevalence rates, and no lineages other than TCI and TCIIa were found in this study in wild monkeys and Rhodnius from the Amazonian region. We characterised TCI and TCIIa from wild primates (16 TCI and five TCIIa), Rhodnius spp. (13 TCI and nine TCIIa), and humans with Chagas disease associated with oral transmission (14 TCI and five TCIIa) in Brazilian Amazonia. To our knowledge, TCIIa had not been associated with wild monkeys until now. Polymorphisms of ssrDNA, cytochrome b gene sequences and randomly amplified polymorphic DNA (RAPD) patterns clearly separated TCIIa from TCIIb-e and TCI lineages, and disclosed small intra-lineage polymorphisms amongst isolates from Amazonia. These data are important in understanding the complexity of the transmission cycles, genetic structure, and evolutionary history of T. cruzi populations circulating in Amazonia, and they contribute to both the unravelling of human infection routes and the pathological peculiarities of Chagas disease in this region.

  15. Incidence of cervical disease associated to HPV in human immunodeficiency infected women under highly active antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Mogtomo Martin

    2009-06-01

    Full Text Available Abstract Background Women infected with human immunodeficiency virus (HIV may be at higher risk of developing cervical cancer than non infected women. In a pilot study, we assessed the relationships among cervical cytology abnormalities associated to Human Papillomavirus (HPV, HIV infection and Highly Active Antiretroviral Therapy (HAART on the development of Squamous Intraepithelial lesions (SILs. Out of the 70 HIV infected women from Douala -Cameroon (Central Africa that we included in the study, half (35 were under HAART. After obtaining information related to their lifestyle and sexual behaviour, cervicovaginal samples for Pap smears and venous blood for CD4 count were collected and further divided into two groups based upon the presence or absence of cervical cytology abnormalities i.e. those with normal cervical cytology and those with low and high Squamous Intraepithelial lesions (LSIL, HSIL. Results Assessment was done according to current antiretroviral regimens available nationwide and CD4 count. It was revealed that 44.3% of HIV-infected women had normal cytology. The overall prevalence of LSIL and HSIL associated to HPV in the studied groups was 24.3% (17/70 and 31.4% (22/70 respectively. Among the 22 HSIL-positive women, 63.6% (14/22 were not on antiretroviral therapy, while 36.4% (8/22 were under HAART. HIV infected women under HAART with positive HSIL, showed a median CD4+ T cell count of 253.7 +/- 31.7 higher than those without therapy (164.7 +/- 26.1. The incidence of HSIL related to HPV infection within the study group independently of HAART initiation was high. Conclusion These results suggest the need for extension and expansion of the current study in order to evaluate the incidence of HPV infection and cervical cancer among HIV-infected and non HIV- infected women in Cameroon.

  16. Assessing the pathogenic potential of human Nephronophthisis disease-associated NPHP-4 missense mutations in C. elegans.

    Science.gov (United States)

    Masyukova, Svetlana V; Winkelbauer, Marlene E; Williams, Corey L; Pieczynski, Jay N; Yoder, Bradley K

    2011-08-01

    A spectrum of complex oligogenic disorders called the ciliopathies have been connected to dysfunction of cilia. Among the ciliopathies are Nephronophthisis (NPHP), characterized by cystic kidney disease and retinal degeneration, and Meckel-Gruber syndrome (MKS), a gestational lethal condition with skeletal abnormalities, cystic kidneys and CNS malformation. Mutations in multiple genes have been identified in NPHP and MKS patients, and an unexpected finding has been that mutations within the same gene can cause either disorder. Further, there is minimal genotype-phenotype correlation and despite recessive inheritance, numerous patients were identified as having a single heterozygous mutation. This has made it difficult to determine the significance of these mutations on disease pathogenesis and led to the hypothesis that clinical presentation in an individual will be determined by genetic interactions between mutations in multiple cilia-related genes. Here we utilize Caenorhabditis elegans and cilia-associated behavioral and morphologic assays to evaluate the pathogenic potential of eight previously reported human NPHP4 missense mutations. We assess the impact of these mutations on C. elegans NPHP-4 function, localization and evaluate potential interactions with mutations in MKS complex genes, mksr-2 and mksr-1. Six out of eight nphp-4 mutations analyzed alter ciliary function, and three of these modify the severity of the phenotypes caused by disruption of mksr-2 and mksr-1. Collectively, our studies demonstrate the utility of C. elegans as a tool to assess the pathogenicity of mutations in ciliopathy genes and provide insights into the complex genetic interactions contributing to the diversity of phenotypes associated with cilia disorders.

  17. β-Amyloid peptides display protective activity against the human Alzheimer's disease-associated herpes simplex virus-1.

    Science.gov (United States)

    Bourgade, Karine; Garneau, Hugo; Giroux, Geneviève; Le Page, Aurélie Y; Bocti, Christian; Dupuis, Gilles; Frost, Eric H; Fülöp, Tamàs

    2015-02-01

    Amyloid plaques, the hallmark of Alzheimer's disease (AD), contain fibrillar β-amyloid (Aβ) 1-40 and 1-42 peptides. Herpes simplex virus 1 (HSV-1) has been implicated as a risk factor for AD and found to co-localize within amyloid plaques. Aβ 1-40 and Aβ 1-42 display anti-bacterial, anti-yeast and anti-viral activities. Here, fibroblast, epithelial and neuronal cell lines were exposed to Aβ 1-40 or Aβ 1-42 and challenged with HSV-1. Quantitative analysis revealed that Aβ 1-40 and Aβ 1-42 inhibited HSV-1 replication when added 2 h prior to or concomitantly with virus challenge, but not when added 2 or 6 h after virus addition. In contrast, Aβ 1-40 and Aβ 1-42 did not prevent replication of the non-enveloped human adenovirus. In comparison, antimicrobial peptide LL-37 prevented HSV-1 infection independently of its sequence of addition. Our findings showed also that Aβ 1-40 and Aβ 1-42 acted directly on HSV-1 in a cell-free system and prevented viral entry into cells. The sequence homology between Aβ and a proximal transmembrane region of HSV-1 glycoprotein B suggested that Aβ interference with HSV-1 replication could involve its insertion into the HSV-1 envelope. Our data suggest that Aβ peptides represent a novel class of antimicrobial peptides that protect against neurotropic enveloped virus infections such as HSV-1. Overproduction of Aβ peptide to protect against latent herpes viruses and eventually against other infections, may contribute to amyloid plaque formation, and partially explain why brain infections play a pathogenic role in the progression of the sporadic form of AD.

  18. IL-4-dependent effector phase in autoimmune exocrinopathy as defined by the NOD.IL-4-gene knockout mouse model of Sjögren's syndrome.

    Science.gov (United States)

    Brayer, J B; Cha, S; Nagashima, H; Yasunari, U; Lindberg, A; Diggs, S; Martinez, J; Goa, J; Humphreys-Beher, M G; Peck, A B

    2001-01-01

    NOD mice manifest many features of autoimmune exocrinopathy (Sjögren's syndrome), a disease generally characterized by a chronic, progressive immunological attack against the exocrine tissues of the salivary and lacrimal glands. Previous studies using the NOD congenic partner strain, NOD.Igmu(null), defined an important role for B lymphocytes in the development of xerostomia, implicating autoantibodies reactive with the acetylcholine muscarinic receptor (M3R) as the possible effector mechanism. In the present study, we have examined the impact of the cytokine, interleukin (IL)-4, on autoimmune exocrinopathy by using the IL-4 gene knockout (KO) NOD mouse strain, NOD.IL-4-/-. Despite manifesting the physiological aberrations and marked leukocytic infiltration of the salivary glands characteristic of autoimmune xerostomia in NOD mice, the NOD.IL-4-/- mice do not develop xerostomia. However, NOD.IL-4-/- mice that received adoptively transferred T lymphocytes derived from NOD.Igmu-/- mice progress to xerostomia, thereby reversing the defect. While progression or lack of progression to xerostomia correlated with the ability of the NOD.IL-4-/- mice to express detectable anti-M3R autoantibodies, the precise mechanism of how IL-4 influences the development of autoimmune xerostomia remains speculative.

  19. The role of IL-4 and IL-13 in cutaneous Leishmaniasis.

    Science.gov (United States)

    Hurdayal, Ramona; Brombacher, Frank

    2014-10-01

    Murine models of Leishmania major infection in the 1980s revealed two distinct, counter-regulatory populations of CD4(+) T helper (Th) cells, delineated Th1 and Th2, and their archetypal cytokines, interferon gamma (IFN-γ) and interleukin (IL)-4/IL-13, which promoted resistance/susceptibility to infection, respectively. However, the introduction of global cytokine-deficient mice in the 1990s revealed pleiotropic immune-regulatory mechanisms of IL-4 and IL-13 that either controlled or exacerbated disease. This undermined the basic premise that IL-4/IL-13 played paramount roles in facilitating a non-healing Th2 response to Leishmania infection and instead suggested that both IL-4 and IL-13-dependent and IL-4/IL-13-independent factors orchestrate disease outcome. The recent characterization of cell-type specific IL-4Rα deficient mice was initiated to help reconcile these observations and dissect the cell-specific effects of IL-4/IL-13 during infection. In this review, we summarize original and recent findings with regard to the role of IL-4 and IL-13 in cutaneous Leishmaniasis. Using the information discerned from various studies and our conditional IL-4Rα gene-deficient mice, we particularly discuss the double-edged sword IL-4 (and in some Leishmania disease models IL-13) in driving a susceptible Th2 response, their immune cell targets that support healing or non-healing responses and their novel role in mediating a Th1 response during disease.

  20. Signal transduction through the IL-4 and insulin receptor families.

    Science.gov (United States)

    Wang, L M; Keegan, A; Frankel, M; Paul, W E; Pierce, J H

    1995-07-01

    Activation of tyrosine kinase-containing receptors and intracellular tyrosine kinases by ligand stimulation is known to be crucial for mediating initial and subsequent events involved in mitogenic signal transduction. Receptors for insulin and insulin-like growth factor 1 (IGF-1) contain cytoplasmic tyrosine kinase domains that undergo autophosphorylation upon ligand stimulation. Activation of these receptors also leads to pronounced and rapid tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) in cells of connective tissue origin. A related substrate, designated 4PS, is similarly phosphorylated by insulin and IGF-1 stimulation in many hematopoietic cell types. IRS-1 and 4PS possess a number of tyrosine phosphorylation sites that are within motifs that bind specific SH2-containing molecules known to be involved in mitogenic signaling such as PI-3 kinase, SHPTP-2 (Syp) and Grb-2. Thus, they appear to act as docking substrates for a variety of signaling molecules. The majority of hematopoietic cytokines bind to receptors that do not possess intrinsic kinase activity, and these receptors have been collectively termed as members of the hematopoietin receptor superfamily. Despite their lack of tyrosine kinase domains, stimulation of these receptors has been demonstrated to activate intracellular kinases leading to tyrosine phosphorylation of multiple substrates. Recent evidence has demonstrated that activation of different members of the Janus family of tyrosine kinases is involved in mediating tyrosine phosphorylation events by specific cytokines. Stimulation of the interleukin 4 (IL-4) receptor, a member of the hematopoietin receptor superfamily, is thought to result in activation of Jak1, Jak3, and/or Fes tyrosine kinases.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Butyrate enhances antibacterial effects while suppressing other features of alternative activation in IL-4-induced macrophages.

    Science.gov (United States)

    Fernando, Maria R; Saxena, Alpana; Reyes, José-Luis; McKay, Derek M

    2016-05-15

    The short-chain fatty acid butyrate is produced by fermentation of dietary fiber by the intestinal microbiota; butyrate is the primary energy source of colonocytes and has immunomodulatory effects. Having shown that macrophages differentiated with IL-4 [M(IL-4)s] can suppress colitis, we hypothesized that butyrate would reinforce an M(IL-4) phenotype. Here, we show that in the presence of butyrate M(IL-4)s display reduced expression of their hallmark markers Arg1 and Ym1 and significantly suppressed LPS-induced nitric oxide, IL-12p40, and IL-10 production. Butyrate treatment likely altered the M(IL-4) phenotype via inhibition of histone deacetylation. Functionally, M(IL-4)s treated with butyrate showed increased phagocytosis and killing of bacteria, compared with M(IL-4) and this was not accompanied by enhanced proinflammatory cytokine production. Culture of regulatory T cells with M(IL-4)s and M(IL-4 + butyrate)s revealed that both macrophage subsets suppressed expression of the regulatory T-cell marker Foxp3. However, Tregs cocultured with M(IL-4 + butyrate) produced less IL-17A than Tregs cocultured with M(IL-4). These data illustrate the importance of butyrate, a microbial-derived metabolite, in the regulation of gut immunity: the demonstration that butyrate promotes phagocytosis in M(IL-4)s that can limit T-cell production of IL-17A reveals novel aspects of bacterial-host interaction in the regulation of intestinal homeostasis.

  2. Effects of IL-10 and IL-4 on LPS-induced transcription factors (AP-1, NF-IL6 and NF-kappa B) which are involved in IL-6 regulation

    NARCIS (Netherlands)

    Dokter, Willem; Koopmans, S.B.; Vellenga, E

    1996-01-01

    Interleukin-10 (IL-10), like IL-4, is known to inhibit cytokine expression in activated human monocytes. We showed that both IL-10 and IL-4 inhibit LPS-induced IL-6 mRNA and protein expression by inhibiting the transcription rate of the IL-6 gene. The strong inhibition of the IL-6 transcription rate

  3. 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.

  4. Association Between IL-4 and IL-6 Expression Variants and Gastric Cancer Among Portuguese Population

    Directory of Open Access Journals (Sweden)

    Ana Maria Sampaio

    2015-07-01

    Conclusion: IL-6 and IL-4 expression variants seem to have an important role in GC risk mechanisms. This study provides preliminary evidence that IL-4 and IL-6 polymorphisms, although not directly linked to the disease, may be useful tools in the study of this multifactorial disease.

  5. Changes in plasma IL4, TNF-α and CRP in response to regular ...

    African Journals Online (AJOL)

    Administrator

    Objective: To determine effects of passive smoking on plasma IL4, TNFá, and CRP in ... Plasma CRP, IL4 and TNFá were measured using commercially available ELISA kits. ..... with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med 1996;153:530- ... Bronchial Hyperresponsiveness, and Atopy.

  6. NanoUPLC-MS(E) proteomic analysis of osteoclastogenesis downregulation by IL-4.

    Science.gov (United States)

    Freire, Mirna S; Cantuária, Ana Paula C; Lima, Stella M F; Almeida, Jeeser A; Murad, André M; Franco, Octavio L; Rezende, Taia M B

    2016-01-10

    Bone resorption is an important factor in bone homeostasis and imbalance can cause several diseases. In osteoimmunology, IL-4 has been described as an important factor in promoting M2 macrophage profile. In order to shed some light on the effect of IL-4 on osteoclast precursors in the presence of RANKL, cytokines and nitric oxide (NO) production and the proteomic profile were analyzed. The presence of IL-4 in in vitro osteoclastogenesis provides production of TNF-α, IL-1α, IL-1β, IL-10 and IL-12 at basal cell levels. Regarding NO production, IL-4 was sufficient to increase the basal NO levels. Proteomic analyses identified 877 global proteins. IL-4 in in vitro RANKL-mediated osteoclastogenesis leads to the expression of 118 proteins. The presence of rIL-4 in in vitro rRANKL-mediated-osteoclastogenesis downregulated this process. However, the proteomics findings in the osteoclastogenesis demonstrated a much greater effect on osteoclast precursor cells than on RANKL-differentiated osteoclasts. These results suggest that the main effect of IL-4 in pre-osteoclast cells leads to a M2 macrophage activation, and this probably contributed to a reduction in osteoclastogenesis when both stimuli were used. This study noticed that IL-4 plays an important regulatory role in bone homeostasis due to its suppressive potential of precursor osteoclast cells.

  7. IL-4 confers resistance to IL-27-mediated suppression on CD4+ T cells by impairing STAT1 signaling

    Science.gov (United States)

    Chen, Zhihong; Wang, Shanze; Erekosima, Nkiruka; Li, Yapeng; Hong, Jessie; Qi, Xiaopeng; Merkel, Patricia; Nagabhushanam, Vijaya; Choo, Eugene; Katial, Rohit; Alam, Rafeul; Trikha, Anita; Chu, HongWei; Zhuang, Yonghua; Jin, Meiling; Bai, Chunxue; Huang, Hua

    2013-01-01

    Background Th2 cells play a critical role in the pathogenesis of allergic asthma. Established Th2 cells have been shown to resist reprogramming into Th1 cells. The inherent stability of Th2 cells poses a significant barrier to treating allergic diseases. Objective We sought to understand the mechanisms by which CD4+ T cells from asthmatic patients resist the IL-27-mediated inhibition. Methods We isolated and cultured CD4+ T cells from both healthy individuals and allergic asthmatic patients in order to test whether IL-27 can inhibit IL-4 production by the cultured CD4+ T cells using ELISA. Culturing conditions that resulted in resistance to IL-27 were determined using both murine and human CD4+ T cell culture systems. STAT1 phosphorylation was analyzed by Western blot and flow cytometry. Suppressor of cytokine signaling (Socs) mRNA expression was measured by quantitative PCR. The small interfering RNA method was used to knockdown the expression of Socs3 mRNA. Main Results We demonstrated that CD4+ T cells from asthmatic patients resisted the suppression of IL-4 production mediated by IL-27. We observed that repeated exposure to Th2-inducing conditions rendered healthy human CD4+ T cells resistant to IL-27-mediated inhibition. Using an in vitro murine culture system, we further demonstrated that repeated or higher doses of IL-4 stimulation, but not IL-2 stimulation, upregulated Socs3 mRNA expression and impaired IL-27-induced STAT1 phosphorylation. The Knockdown of Socs3 mRNA expression restored IL-27-induced STAT1 phosphorylation and IL-27-mediated inhibition of IL-4-production. Conclusions Our findings demonstrate that differentiated Th2 cells can resist IL-27-induced reprogramming toward Th1 cells by downregulating STAT1 phosphorylation and likely explain why the CD4+ T cells of asthmatic patients are resistant to IL-27-mediated inhibition. PMID:23958647

  8. Oligonucleotide fishing for STAT6: cross-talk between IL-4 and chemokines

    DEFF Research Database (Denmark)

    Eriksen, K W; Nielsen, M; Kaltoft, K

    2001-01-01

    Signal transducer and activator of transcription 6 (STAT6) is essential for the biological activities of interleukin-4 (IL-4) and the development of allergic responses in mice. Here we report on a sensitive and specific assay for STAT6 activation in response to IL-4. We took advantage of double-stranded...... oligonucleotide probes containing a STAT6-binding gene-sequence from the promotor of the immunoglobulin heavy chain germline epsilon transcript to study the IL-4-induced DNA binding of STAT6. Using these probes, we show that repeated adjacent STAT6-binding sites result in enhanced STAT6-DNA binding. Moreover......, the distance between the binding sites is critical for STAT-DNA binding, i.e. STAT6 binding is decreased at distances above 20 nucleotides between neighbouring binding sites. Using this assay to study cross-talk between IL-4 and chemokines, we provide evidence that MIP-1beta and MIG inhibit IL-4-induced STAT6...

  9. Critical role of p38 MAPK in IL-4-induced alternative activation of peritoneal macrophages.

    Science.gov (United States)

    Jiménez-Garcia, Lidia; Herránz, Sandra; Luque, Alfonso; Hortelano, Sonsoles

    2015-01-01

    Alternative activation of macrophages plays an important role in a range of physiological and pathological processes. This alternative phenotype, also known as M2 macrophages, is induced by type 2 cytokines such as IL-4. The binding of IL-4 to its receptor leads to activation of two major signaling pathways: STAT-6 and PI3K. However, recent studies have described that p38 MAPK might play a role in IL-4-dependent signaling in some cells, although its role in macrophages is still controversial. In this study, we investigated whether p38 MAPK plays a role in the polarization of macrophages in mice. Our results reveal that IL-4 induces phosphorylation of p38 MAPK in thioglycollate-elicited murine peritoneal macrophages, in addition to STAT-6 and PI3K activation. Furthermore, p38 MAPK inactivation, by gene silencing or pharmacological inhibition, suppressed IL-4-induced typical M2 markers, indicating the involvement of p38 MAPK in the signaling of IL-4 leading to M2-macrophage polarization. Moreover, p38 MAPK inhibition blocked phosphorylation of STAT-6 and Akt, suggesting that p38 MAPK is upstream of these signaling pathways. Finally, we show that in an in vivo model of chitin-induced M2 polarization, p38 MAPK inhibition also diminished activation of M2 markers. Taken together, our data establish a new role for p38 MAPK during IL-4-induced alternative activation of macrophages. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. IRS-1: essential for insulin- and IL-4-stimulated mitogenesis in hematopoietic cells.

    Science.gov (United States)

    Wang, L M; Myers, M G; Sun, X J; Aaronson, S A; White, M; Pierce, J H

    1993-09-17

    Although several interleukin-3 (IL-3)-dependent cell lines proliferate in response to IL-4 or insulin, the 32D line does not. Insulin and IL-4 sensitivity was restored to 32D cells by expression of IRS-1, the principal substrate of the insulin receptor. Although 32D cells possessed receptors for both factors, they lacked the IRS-1--related protein, 4PS, which becomes phosphorylated by tyrosine in insulin- or IL-4--responsive lines after stimulation. These results indicate that factors that bind unrelated receptors can use similar mitogenic signaling pathways in hematopoietic cells and that 4PS and IRS-1 are functionally similar proteins that are essential for insulin- and IL-4--induced proliferation.

  11. Modulation of mouse macrophage polarization in vitro using IL-4 delivery by osmotic pumps.

    Science.gov (United States)

    Pajarinen, Jukka; Tamaki, Yasunobu; Antonios, Joseph K; Lin, Tzu-Hua; Sato, Taishi; Yao, Zhenyu; Takagi, Michiaki; Konttinen, Yrjö T; Goodman, Stuart B

    2015-04-01

    Modulation of macrophage polarization is emerging as promising means to mitigate wear particle-induced inflammation and periprosthetic osteolysis. As a model for continuous local drug delivery, we used miniature osmotic pumps to deliver IL-4 in order to modulate macrophage polarization in vitro from nonactivated M0 and inflammatory M1 phenotypes towards a tissue regenerative M2 phenotype. Pumps delivered IL-4 into vials containing mouse bone marrow macrophage (mBMM) media. This conditioned media (CM) was collected at seven day intervals up to four weeks (week 1 to week 4 samples). IL-4 concentration in the CM was determined by ELISA and its biological activity was assayed by exposing M0 and M1 mBMMs to week 1 or week 4 CM. The IL-4 concentration in the CM approximated the mathematically calculated amount, and its biological activity was well retained, as both M0 and M1 macrophages exposed to either the week 1 or week 4 CM assumed M2-like phenotype as determined by qRT-PCR, ELISA, and immunocytochemistry. The results show that IL-4 can be delivered using osmotic pumps and that IL-4 delivered can modulate macrophage phenotype. Results build a foundation for in vivo studies using our previously validated animal models and provide possible strategies to locally mitigate wear particle-induced macrophage activation and periprosthetic osteolysis.

  12. IL-4Rα-Associated Antigen Processing by B Cells Promotes Immunity in Nippostrongylus brasiliensis Infection

    Science.gov (United States)

    Hoving, Jennifer C.; Nieuwenhuizen, Natalie; McSorley, Henry J.; Ndlovu, Hlumani; Bobat, Saeeda; Kimberg, Matti; Kirstein, Frank; Cutler, Anthony J.; DeWals, Benjamin; Cunningham, Adam F.; Brombacher, Frank

    2013-01-01

    In this study, B cell function in protective TH2 immunity against N. brasiliensis infection was investigated. Protection against secondary infection depended on IL-4Rα and IL-13; but not IL-4. Protection did not associate with parasite specific antibody responses. Re-infection of B cell-specific IL-4Rα−/− mice resulted in increased worm burdens compared to control mice, despite their equivalent capacity to control primary infection. Impaired protection correlated with reduced lymphocyte IL-13 production and B cell MHC class II and CD86 surface expression. Adoptive transfer of in vivo N. brasiliensis primed IL-4Rα expressing B cells into naïve BALB/c mice, but not IL-4Rα or IL-13 deficient B cells, conferred protection against primary N. brasiliensis infection. This protection required MHC class II compatibility on B cells suggesting cognate interactions by B cells with CD4+ T cells were important to co-ordinate immunity. Furthermore, the rapid nature of these protective effects by B cells suggested non-BCR mediated mechanisms, such as via Toll Like Receptors, was involved, and this was supported by transfer experiments using antigen pulsed Myd88−/− B cells. These data suggest TLR dependent antigen processing by IL-4Rα-responsive B cells producing IL-13 contribute significantly to CD4+ T cell-mediated protective immunity against N. brasiliensis infection. PMID:24204255

  13. IL-4 Deficiency Decreases Mortality but Increases Severity of Arthritis in Experimental Group B Streptococcus Infection

    Directory of Open Access Journals (Sweden)

    Luciana Tissi

    2009-01-01

    Full Text Available IL-4 is an anti-inflammatory cytokine that inhibits the onset and severity in different experimental arthritis models. Group B streptococci (GBS have been recognized as an ever-growing cause of serious invasive infections in nonpregnant adults. Septic arthritis is a clinical manifestation of GBS infection. To investigate the role of IL-4 in experimental GBS infection, IL-4 deficient or competent mice were inoculated with 1×107 GBS/mouse. Mortality, appearance of arthritis, GBS growth in the organs, and local and systemic cytokine and chemokine production were examined. IL-4–/– mice showed lower mortality rates but increased severity of arthritis and exhibited a lower microbial load in blood, kidneys, and joints than wt mice. Increased local levels of IL-1 β, IL-6, TNF-α, MIP-1α, and MIP-2 accompanied the more severe arthritis in IL-4–/– mice. Our results suggest a detrimental role of IL-4 in GBS sepsis, whereas it plays a beneficial effect on GBS-induced arthritis.

  14. Human risk of diseases associated with red meat intake: Analysis of current theories and proposed role for metabolic incorporation of a non-human sialic acid.

    Science.gov (United States)

    Alisson-Silva, Frederico; Kawanishi, Kunio; Varki, Ajit

    2016-10-01

    One of the most consistent epidemiological associations between diet and human disease risk is the impact of red meat consumption (beef, pork, and lamb, particularly in processed forms). While risk estimates vary, associations are reported with all-cause mortality, colorectal and other carcinomas, atherosclerotic cardiovascular disease, type II diabetes, and possibly other inflammatory processes. There are many proposed explanations for these associations, some long discussed in the literature. Attempts to explain the effects of red meat consumption have invoked various red meat-associated agents, including saturated fat, high salt intake, Trimethylamine-N-oxide (TMAO) generation by microbiota, and environmental pollutants contaminating red meat, none of which are specific for red meat. Even the frequently mentioned polycyclic aromatic carcinogens arising from high temperature cooking methods are not red meat specific, as these are also generated by grilling poultry or fish, as well as by other forms of cooking. The traditional explanations that appear to be more red meat specific invoke the impact of N-nitroso compounds, heme iron, and the potential of heme to catalyze endogenous nitrosation. However, heme can be denatured by cooking, high levels of plasma hemopexin will block its tissue delivery, and much higher amounts of heme likely originate from red blood cell breakdown in vivo. Therefore, red meat-derived heme could only contribute to colorectal carcinoma risk, via direct local effects. Also, none of these mechanisms explain the apparent human propensity i.e., other carnivores have not been reported at high risk for all these diseases. A more recently proposed hypothesis involves infectious agents in beef from specific dairy cattle as agents of colorectal cancer. We have also described another mechanistic explanation for the human propensity for risk of red-meat associated diseases that is consistent with most observations: metabolic incorporation of a non-human

  15. Nippostrongylus-induced intestinal hypercontractility requires IL-4 receptor alpha-responsiveness by T cells in mice.

    Directory of Open Access Journals (Sweden)

    Saskia Schmidt

    Full Text Available Gut-dwelling helminthes induce potent IL-4 and IL-13 dominated type 2 T helper cell (T(H2 immune responses, with IL-13 production being essential for Nippostrongylus brasiliensis expulsion. This T(H2 response results in intestinal inflammation associated with local infiltration by T cells and macrophages. The resulting increased IL-4/IL-13 intestinal milieu drives goblet cell hyperplasia, alternative macrophage activation and smooth muscle cell hypercontraction. In this study we investigated how IL-4-promoted T cells contributed to the parasite induced effects in the intestine. This was achieved using pan T cell-specific IL-4 receptor alpha-deficient mice (iLck(creIL-4Rα(-/lox and IL-4Rα-responsive control mice. Global IL-4Rα(-/- mice showed, as expected, impaired type 2 immunity to N. brasiliensis. Infected T cell-specific IL-4Rα-deficient mice showed comparable worm expulsion, goblet cell hyperplasia and IgE responses to control mice. However, impaired IL-4-promoted T(H2 cells in T cell-specific IL-4Rα deficient mice led to strikingly reduced IL-4 production by mesenteric lymph node CD4(+ T cells and reduced intestinal IL-4 and IL-13 levels, compared to control mice. This reduced IL-4/IL-13 response was associated with an impaired IL-4/IL-13-mediated smooth muscle cell hypercontractility, similar to that seen in global IL-4Rα(-/- mice. These results demonstrate that IL-4-promoted T cell responses are not required for the resolution of a primary N. brasiliensis infection. However, they do contribute significantly to an important physiological manifestation of helminth infection; namely intestinal smooth muscle cell-driven hypercontractility.

  16. IL-4 directly signals tissue-resident macrophages to proliferate beyond homeostatic levels controlled by CSF-1

    Science.gov (United States)

    Ruckerl, Dominik; Thomas, Graham D.; Hewitson, James P.; Duncan, Sheelagh; Brombacher, Frank; Maizels, Rick M.; Hume, David A.; Allen, Judith E.

    2013-01-01

    Macrophages (MΦs) colonize tissues during inflammation in two distinct ways: recruitment of monocyte precursors and proliferation of resident cells. We recently revealed a major role for IL-4 in the proliferative expansion of resident MΦs during a Th2-biased tissue nematode infection. We now show that proliferation of MΦs during intestinal as well as tissue nematode infection is restricted to sites of IL-4 production and requires MΦ-intrinsic IL-4R signaling. However, both IL-4Rα–dependent and –independent mechanisms contributed to MΦ proliferation during nematode infections. IL-4R–independent proliferation was controlled by a rise in local CSF-1 levels, but IL-4Rα expression conferred a competitive advantage with higher and more sustained proliferation and increased accumulation of IL-4Rα+ compared with IL-4Rα− cells. Mechanistically, this occurred by conversion of IL-4Rα+ MΦs from a CSF-1–dependent to –independent program of proliferation. Thus, IL-4 increases the relative density of tissue MΦs by overcoming the constraints mediated by the availability of CSF-1. Finally, although both elevated CSF1R and IL-4Rα signaling triggered proliferation above homeostatic levels, only CSF-1 led to the recruitment of monocytes and neutrophils. Thus, the IL-4 pathway of proliferation may have developed as an alternative to CSF-1 to increase resident MΦ numbers without coincident monocyte recruitment. PMID:24101381

  17. Plasma Level of IL-4 Differs in Patients Infected with Different Modern Lineages of M. tuberculosis

    Directory of Open Access Journals (Sweden)

    Adane Mihret

    2012-01-01

    Full Text Available Epidemiological evidence from tuberculosis outbreaks revealed that some genotypes of M. tuberculosis are more transmissible and capable of causing disease than others. We analysed the plasma cytokine levels of pulmonary tuberculosis patients infected with different strains of M. tuberculosis to test the hypothesis that immune responses would be linked to the bacterial genotype. Spoligotyping was carried out for genotyping, and we used Luminex technology to measure 17 cytokines (EGF, fractalkine, GM-CSF, IFN-γ, IL-1, IL-10, IL-12, IL-17, IL-4, IL-7, IL-9, IP-10, MCP-1, MCP-3, MIP-1β, TNF, and VEGF from plasma samples of tuberculosis patients. The levels of IL-12 (p40, IL-4, IL-7, and MIP-1beta were higher in patients infected with lineage 3, however, it was only IL-4 which showed statistically significant difference (P<0.05 between lineage 3 and lineage 4. We further grouped the lineages into families (CAS, H and T families, and we found that the plasma level of IL-4 was significantly higher in patients infected with the CAS family (P<0.05 in comparison with T and H families. However, there was no difference between T and H families. Therefore, the higher level of IL-4 in lineage 3 families might indicate that possible differences in the response elicited from host depend on strain lineages in the studied population.

  18. IL-4 gene expression in adventitial layer (fibrous layer) of hepatic ovine and bovine hydatid cysts.

    Science.gov (United States)

    Dorosti, Zahra; Tolouei, Sepideh; Khanahmad, Hossein; Jafari, Rasool; Jafaee, Fereshteh; Sharafi, Seyedeh Marayam; Darani, Hossein Yousofi

    2016-09-01

    Cystic Echinococcosis is a parasitic disease with cosmopolitan distribution caused by the tape worm Echinococcus granulosus. Fibrous layer is developed around the cyst as a host immune response reaction. The aim of this study was to evaluate the rate of IL-4 gene expression in fibrous layer of bovine and ovine hepatic hydatid cysts using quantitative technique of Real-Time PCR. In this descriptive study the samples of hydatid cyst fibrous layer were taken from 6 bovine and 6 ovine hepatic hydatid cysts. Samples of normal liver tissue close to the cyst were also taken as controls. Total RNA from each sample was extracted and then converted to cDNA. Afterward, the rate of IL-4 gene expression for each sample was evaluated using real-time PCR technique. Data were analyzed by REST software (version 2.0.13, 2009). In sheep the rate of IL-4 gene expression in the fibrous layer of hepatic hydatid cysts was 1.98 times more than the rate of IL4 gene expression in control samples, but the difference was not significant (P = 0.561). In cattle the rate of IL-4 gene expression in the fibrous layer of hepatic hydatid cysts was 9.84 times more than that of control samples which was statistically significant (P layer of bovine hydatid cyst, it can be concluded that this interleukin may play an important role in host parasite relationship.

  19. Biochemical and Genetic Evidence for a SAP-PKC-θ Interaction Contributing to IL-4 Regulation

    Science.gov (United States)

    Cannons, Jennifer L.; Wu, Julie Z.; Gomez-Rodriguez, Julio; Zhang, Jinyi; Dong, Baoxia; Liu, Yin; Shaw, Stephen; Siminovitch, Katherine A.; Schwartzberg, Pamela L.

    2012-01-01

    SAP, an adaptor molecule that recruits Fyn to the SLAM-family of immunomodulatory receptors, is mutated in X-linked lymphoproliferative disease. CD4+ T cells from SAP-deficient mice have defective TCR-induced IL-4 production and impaired T cell-mediated help for germinal center formation; however, the downstream intermediates contributing to these defects remain unclear. We previously found that SAP-deficient CD4+ T cells exhibit decreased PKC-θ recruitment upon TCR stimulation. We demonstrate here using GST-pulldowns and co-immunoprecipitation studies that SAP constitutively associates with PKC-θ in T cells. SAP-PKC-θ interactions required R78 of SAP, a residue previously implicated in Fyn recruitment, yet SAP’s interactions with PKC-θ occurred independent of phosphotyrosine binding and Fyn. Overexpression of SAP in T cells increased and sustained PKC-θ recruitment to the immune synapse and elevated IL-4 production in response to TCR plus SLAM-mediated stimulation. Moreover, PKC-θ, like SAP, was required for SLAM-mediated increases in IL-4 production and conversely, membrane-targeted PKC-θ mutants rescued IL-4 expression in SAP−/− CD4+ T cells, providing genetic evidence that PKC-θ is a critical component of SLAM/SAP-mediated pathways that influence TCR-driven IL-4 production. PMID:20668219

  20. Deletion of IL-4Ralpha on CD4 T cells renders BALB/c mice resistant to Leishmania major infection.

    Directory of Open Access Journals (Sweden)

    Magdalena Radwanska

    2007-05-01

    Full Text Available Effector responses induced by polarized CD4+ T helper 2 (Th2 cells drive nonhealing responses in BALB/c mice infected with Leishmania major. Th2 cytokines IL-4 and IL-13 are known susceptibility factors for L. major infection in BALB/c mice and induce their biological functions through a common receptor, the IL-4 receptor alpha chain (IL-4Ralpha. IL-4Ralpha-deficient BALB/c mice, however, remain susceptible to L. major infection, indicating that IL-4/IL-13 may induce protective responses. Therefore, the roles of polarized Th2 CD4+ T cells and IL-4/IL-13 responsiveness of non-CD4+ T cells in inducing non-healer or healer responses have yet to be elucidated. CD4+ T cell-specific IL-4Ralpha (Lck(creIL-4Ralpha(-/lox deficient BALB/c mice were generated and characterized to elucidate the importance of IL-4Ralpha signaling during cutaneous leishmaniasis in the absence of IL-4-responsive CD4+ T cells. Efficient deletion was confirmed by loss of IL-4Ralpha expression on CD4+ T cells and impaired IL-4-induced CD4+ T cell proliferation and Th2 differentiation. CD8+, gammadelta+, and NK-T cells expressed residual IL-4Ralpha, and representative non-T cell populations maintained IL-4/IL-13 responsiveness. In contrast to IL-4Ralpha(-/lox BALB/c mice, which developed ulcerating lesions following infection with L. major, Lck(creIL-4Ralpha(-/lox mice were resistant and showed protection to rechallenge, similar to healer C57BL/6 mice. Resistance to L. major in Lck(creIL-4Ralpha(-/lox mice correlated with reduced numbers of IL-10-secreting cells and early IL-12p35 mRNA induction, leading to increased delayed type hypersensitivity responses, interferon-gamma production, and elevated ratios of inducible nitric oxide synthase mRNA/parasite, similar to C57BL/6 mice. These data demonstrate that abrogation of IL-4 signaling in CD4+ T cells is required to transform non-healer BALB/c mice to a healer phenotype. Furthermore, a beneficial role for IL-4Ralpha signaling in L

  1. IL-4Ralpha-independent expression of mannose receptor and Ym1 by macrophages depends on their IL-10 responsiveness.

    Directory of Open Access Journals (Sweden)

    Benjamin G Dewals

    2010-05-01

    Full Text Available IL-4Ralpha-dependent responses are essential for granuloma formation and host survival during acute schistosomiasis. Previously, we demonstrated that mice deficient for macrophage-specific IL-4Ralpha (LysM(creIl4ra(-/lox developed increased hepatotoxicity and gut inflammation; whereas inflammation was restricted to the liver of mice lacking T cell-specific IL-4Ralpha expression (iLck(creIl4ra(-/lox. In the study presented here we further investigated their role in liver granulomatous inflammation. Frequencies and numbers of macrophage, lymphocyte or granulocyte populations, as well as Th1/Th2 cytokine responses were similar in Schistosoma mansoni-infected LysM(creIl4ra(-/lox liver granulomas, when compared to Il4ra(-/lox control mice. In contrast, a shift to Th1 responses with high IFN-gamma and low IL-4, IL-10 and IL-13 was observed in the severely disrupted granulomas of iLck(creIl4ra(-/lox and Il4ra(-/- mice. As expected, alternative macrophage activation was reduced in both LysM(creIl4ra(-/lox and iLck(creIl4ra(-/lox granulomas with low arginase 1 and heightened nitric oxide synthase RNA expression in granuloma macrophages of both mouse strains. Interestingly, a discrete subpopulation of SSC(highCD11b+I-A/I-E(highCD204+ macrophages retained expression of mannose receptor (MMR and Ym1 in LysM(creIl4ra(-/lox but not in iLck(creIl4ra(-/lox granulomas. While aaMphi were in close proximity to the parasite eggs in Il4ra(-/lox control mice, MMR+Ym1+ macrophages in LysM(creIl4ra(-/lox mice were restricted to the periphery of the granuloma, indicating that they might have different functions. In vivo IL-10 neutralisation resulted in the disappearance of MMR+Ym1+ macrophages in LysM(creIl4ra(-/lox mice. Together, these results show that IL-4Ralpha-responsive T cells are essential to drive alternative macrophage activation and to control granulomatous inflammation in the liver. The data further suggest that in the absence of macrophage-specific IL-4

  2. Oligonucleotide fishing for STAT6: cross-talk between IL-4 and chemokines

    DEFF Research Database (Denmark)

    Eriksen, K W; Nielsen, M; Kaltoft, K;

    2001-01-01

    , the distance between the binding sites is critical for STAT-DNA binding, i.e. STAT6 binding is decreased at distances above 20 nucleotides between neighbouring binding sites. Using this assay to study cross-talk between IL-4 and chemokines, we provide evidence that MIP-1beta and MIG inhibit IL-4-induced STAT6...... activation, whereas other chemokines and cytokines do not. In conclusion, our data show that oligonucleotide fishing is a supplementary tool for studying cytokine cross-talk at a genomic level....

  3. Expression of POSTN, IL-4, and IL-13 in Chronic Rhinosinusitis with Nasal Polyps.

    Science.gov (United States)

    Milonski, Jaroslaw; Zielinska-Blizniewska, Hanna; Majsterek, Ireneusz; Przybyłowska-Sygut, Karolina; Sitarek, Przemyslaw; Korzycka-Zaborowska, Barbara; Olszewski, Jurek

    2015-05-01

    Chronic rhinosinusitis with nasal polyps (CRSwNP) is one of the most frequently encountered chronic nasal diseases with a significant impact on patient quality of life. The aim of our study was therefore to investigate the association between the POSTN, IL-4, and IL-13 gene expression and the nasal polyp development. The objective of this study was to determine differential expression of POSTN, IL-4, and IL-13 genes in the mucosa and polyps of 63 patients with CRSwNP and 23 chronic rhinosinusitis (CRS) without nasal polyps (CRSsNP) when compared with patients with nasal septum deviation (n=18) who were used as controls. The expression level was investigated using reverse transcription-polymerase chain reaction assays in the polyp tissue and the mucosa of paranasal sinus collected while undergoing functional endoscopic sinus surgery. Expression of the mRNAs of all three genes, IL-4, IL-13, and POSTN, was significantly greater in the paired tissues of CRS patients with NPs or without NPs than in control subjects, with highest levels of POSTN and IL-13 seen in CRSwNP. An increased level of POSTN, IL-4, and IL-13 gene expression may be related to the development of chronic rhinosinusitis with nasal polyps, but polyp formation seemed to be associated especially with POSTN and IL-13 expression.

  4. Basal chromatin modification at the IL-4 gene in helper T cells

    Energy Technology Data Exchange (ETDEWEB)

    Grogan, Jane L.; Wang, Zhi-En; Stanley, Sarah; Harmon, Brian; Loots, Gaby G.; Rubin, Edward M.; Locksley, Richard M.

    2003-04-15

    Chromatin immunoprecipitations in naive CD4, but not CD8, T cells, demonstrated association of the IL-4 promoter with acetylated histone. Histone modifications and rapid IL-4 transcription were absent in conserved noncoding sequence 1 (CNS-1){sup -/-} cells lacking an 8-kb-distant enhancer in the IL-4/IL-13 intergenic region, but also in CD4{sup -/-} and Itk{sup -/-} cells, which have similar Th2 deficiencies. Histones associated with the IL-13 promoter were not similarly acetylated in naive T cells, but became acetylated in differentiated Th2 cells. Conversely, Th1 differentiation induced histone methylation at the type 2 cytokine locus. Like CD4{sup -/-} and Itk{sup -/-} mice, CNS-1{sup -/-} BALB/c mice were highly resistant to the Th2-inducing protozoan, Leishmania major. CNS-1 deficiency led to failure of IL-4 gene repositioning to heterochromatin after Th1 polarization, possibly related to the presence of reiterative Ikaros binding sites in the intergenic element. Hyperacetylation of nonexpressed genes may serve to mark lineage-specific loci for rapid expression and further modification.

  5. The differential expression of IL-4 and IL-13 and its impact on type-2 immunity.

    Science.gov (United States)

    Bao, Katherine; Reinhardt, R Lee

    2015-09-01

    Allergic disease represents a significant global health burden, and disease incidence continues to rise in urban areas of the world. As such, a better understanding of the basic immune mechanisms underlying disease pathology are key to developing therapeutic interventions to both prevent disease onset as well as to ameliorate disease morbidity in those individuals already suffering from a disorder linked to type-2 inflammation. Two factors central to type-2 immunity are interleukin (IL)-4 and IL-13, which have been linked to virtually all major hallmarks associated with type-2 inflammation. Therefore, IL-4 and IL-13 and their regulatory pathways represent ideal targets to suppress disease. Despite sharing many common regulatory pathways and receptors, these cytokines perform very distinct functions during a type-2 immune response. This review summarizes the literature surrounding the function and expression of IL-4 and IL-13 in CD4+ T cells and innate immune cells. It highlights recent findings in vivo regarding the differential expression and non-canonical regulation of IL-4 and IL-13 in various immune cells, which likely play important and underappreciated roles in type-2 immunity.

  6. High salt reduces the activation of IL-4- and IL-13-stimulated macrophages.

    Science.gov (United States)

    Binger, Katrina J; Gebhardt, Matthias; Heinig, Matthias; Rintisch, Carola; Schroeder, Agnes; Neuhofer, Wolfgang; Hilgers, Karl; Manzel, Arndt; Schwartz, Christian; Kleinewietfeld, Markus; Voelkl, Jakob; Schatz, Valentin; Linker, Ralf A; Lang, Florian; Voehringer, David; Wright, Mark D; Hubner, Norbert; Dechend, Ralf; Jantsch, Jonathan; Titze, Jens; Müller, Dominik N

    2015-11-01

    A high intake of dietary salt (NaCl) has been implicated in the development of hypertension, chronic inflammation, and autoimmune diseases. We have recently shown that salt has a proinflammatory effect and boosts the activation of Th17 cells and the activation of classical, LPS-induced macrophages (M1). Here, we examined how the activation of alternative (M2) macrophages is affected by salt. In stark contrast to Th17 cells and M1 macrophages, high salt blunted the alternative activation of BM-derived mouse macrophages stimulated with IL-4 and IL-13, M(IL-4+IL-13) macrophages. Salt-induced reduction of M(IL-4+IL-13) activation was not associated with increased polarization toward a proinflammatory M1 phenotype. In vitro, high salt decreased the ability of M(IL-4+IL-13) macrophages to suppress effector T cell proliferation. Moreover, mice fed a high salt diet exhibited reduced M2 activation following chitin injection and delayed wound healing compared with control animals. We further identified a high salt-induced reduction in glycolysis and mitochondrial metabolic output, coupled with blunted AKT and mTOR signaling, which indicates a mechanism by which NaCl inhibits full M2 macrophage activation. Collectively, this study provides evidence that high salt reduces noninflammatory innate immune cell activation and may thus lead to an overall imbalance in immune homeostasis.

  7. Polyunsaturated fatty acids support epithelial barrier integrity and reduce IL-4 mediated permeability in vitro.

    NARCIS (Netherlands)

    Willemsen, L.E.M.; Koetsier, Marjolein; Balvers, M.; Beermann, C.; Stahl, B.; Tol, EA van

    2008-01-01

    BACKGROUND: The intestinal mucosa functions as a barrier against harmful dietary and microbial antigens. An intact gut barrier forms a prerequisite for protection against infection and allergy. Both allergic and inflammatory mediators (e.g. IL-4, IFN-gamma) are known to compromise the epithelial

  8. Healthy individuals that control a latent infection with Mycobacterium tuberculosis express high levels of Th1 cytokines and the IL-4 antagonist IL-4delta2.

    Science.gov (United States)

    Demissie, Abebech; Abebe, Markos; Aseffa, Abraham; Rook, Graham; Fletcher, Helen; Zumla, Alimuddin; Weldingh, Karin; Brock, Inger; Andersen, Peter; Doherty, T Mark

    2004-06-01

    The majority of healthy individuals exposed to Mycobacterium tuberculosis will not develop disease and identifying what constitutes "protective immunity" is one of the holy grails of M. tuberculosis immunology. It is known that IFN-gamma is essential for protection, but it is also apparent that IFN-gamma levels alone do not explain the immunity/susceptibility dichotomy. The controversy regarding correlates of immunity persists because identifying infected but healthy individuals (those who are immune) has been problematic. We have therefore used recognition of the M. tuberculosis virulence factor early secretory antigenic target 6 to identify healthy, but infected individuals from tuberculosis (TB)-endemic and nonendemic regions (Ethiopia and Denmark) and have compared signals for cytokines expressed directly ex vivo with the pattern found in TB patients. We find that TB patients are characterized by decreased levels of Th1 cytokines and increased levels of IL-10 compared with the healthy infected and noninfected community controls. Interestingly, the healthy infected subjects exhibited a selective increase of message for the IL-4 antagonist, IL-4delta2, compared with both TB patients or noninfected individuals. These data suggest that long-term control of M. tuberculosis infection is associated not just with elevated Th1 responses but also with inhibition of the Th2 response.

  9. The location of a disease-associated polymorphism and genomic structure of the human 52-kDa Ro/SSA locus (SSA1)

    Energy Technology Data Exchange (ETDEWEB)

    Tsugu, H.; Horowitz, R.; Gibson, N. [Univ. of Oklahoma Health Sciences Center, Oklahoma City, OK (United States)] [and others

    1994-12-01

    Sera from approximately 30% of patients with systemic lupus erythematosus (SLE) contain high titers of autoantibodies that bind to the 52-kDa Ro/SSA protein. We previously detected polymorphisms in the 52-kDa Ro/SSA gene (SSA1) with restriction enzymes, one of which is strongly associated with the presence of SLE (P < 0.0005) in African Americans. A higher disease frequency and more severe forms of the disease are commonly noted among these female patients. To determine the location and nature of this polymorphism, we obtained two clones that span 8.5 kb of the 52-kDa Ro/SSA locus including its upstream regulatory region. Six exons were identified, and their nucleotide sequences plus adjacent noncoding regions were determined. No differences were found between these exons and the coding region of one of the reported cDNAs. The disease-associated polymorphic site suggested by a restriction enzyme map and confirmed by DNA amplification and nucleotide sequencing was present upstream of exon 1. This polymorphism may be a genetic marker for a disease-related variation in the coding region for the protein or in the upstream regulatory region of this gene. Although this RFLP is present in Japanese, it is not associated with lupus in this race. 41 refs., 4 figs., 2 tabs.

  10. Development of a novel microbubble-liposome complex conjugated with peptide ligands targeting IL4R on brain tumor cells.

    Science.gov (United States)

    Park, See-Hyoung; Yoon, Young Ii; Moon, Hyoungwon; Lee, Ga-Hyun; Lee, Byung-Heon; Yoon, Tae-Jong; Lee, Hak Jong

    2016-07-01

    Gas (SF6)-filled microbubbles (MBs) were prepared by emulsion and solvent-evaporation method. The prepared MBs were further conjugated with doxorubicin (Dox)-loaded nano-sized liposome and peptide ligands to interleukin-4 receptor (IL4R) for targeting brain tumor cells. The final MB-liposome (Dox)-IL4R targeting peptide ligand [MB-Lipo (Dox)-IL4RTP] had a spherical structure with the mean size of 1,500 nm. The MB-Lipo (Dox)‑IL4RTP exhibited cellular uptake in U87MG brain tumor cells (a brain tumor cell line expressing strongly IL4R) with frequency ultrasound energy suggesting that MB-Lipo (Dox)‑IL4RTP provided effective targeting ability for brain tumor cells. In addition, WST-1 assay results showed that MB-Lipo (Dox)‑IL4RTP inhibited the proliferation of U87MG cells IL4R‑dependently. This was confirmed by western blotting of γH2AX, phospho (Ser15)-p53, p53 and p21 which are signal transduction proteins involved in DNA damage response and cell cycle arrest. Taken together, these results indicate that MB-Lipo (Dox)-IL4RTP represents a promising ultrasonic contrast agent for tumor-targeting ultrasonic imaging.

  11. Regulation of the Il4 gene is independently controlled by proximal and distal 3' enhancers in mast cells and basophils.

    Science.gov (United States)

    Yagi, Ryouji; Tanaka, Shinya; Motomura, Yasutaka; Kubo, Masato

    2007-12-01

    Mast cells and basophils are known to be a critical interleukin 4 (IL-4) source for establishing Th2 protective responses to parasitic infections. Chromatin structure and histone modification patterns in the Il13/Il4 locus of mast cells were similar to those of IL-4-producing type 2 helper T cells. However, using a transgenic approach, we found that Il4 gene expression was distinctly regulated by individual cis regulatory elements in cell types of different lineages. The distal 3' element contained conserved noncoding sequence 2 (CNS-2), which was a common enhancer for memory phenotype T cells, NKT cells, mast cells, and basophils. Targeted deletion of CNS-2 compromised production of IL-4 and several Th2 cytokines in connective-tissue-type and immature-type mast cells but not in basophils. Interestingly, the proximal 3' element containing DNase I-hypersensitive site 4 (HS4), which controls Il4 gene silencing in T-lineage cells, exhibited selective enhancer activity in basophils. These results indicate that CNS-2 is an essential enhancer for Il4 gene transcription in mast cell but not in basophils. The transcription of the Il4 gene in mast cells and basophils is independently regulated by CNS-2 and HS4 elements that may be critical for lineage-specific Il4 gene regulation in these cell types.

  12. Associação dos polimorfismos dos genes TGF-beta1, CD14, IL-4, IL-4R e ADAM33 com a gravidade da asma em crianças e adolescentes Association of TGF-beta1, CD14, IL-4, IL-4R and ADAM33 gene polymorphisms with asthma severity in children and adolescents

    Directory of Open Access Journals (Sweden)

    Isabel C. J. de Faria

    2008-06-01

    Full Text Available OBJETIVO: Verificar, em uma amostra de pacientes com asma atópica persistente leve, moderada e grave, a associação entre os polimorfismos dos genes fator de crescimento transformante-beta1 (TGF-beta1 (C-509T e T869C, CD14 (C-159T, IL-4 (C-590T, IL-4R (ILe50Val e ADAM33 (S_2 com a gravidade da asma. MÉTODOS: Realizou-se um estudo clínico laboratorial prospectivo em pacientes com asma atópica persistente, comparados a um grupo controle no Hospital Universitário da Universidade Estadual de Campinas nos anos de 2006 e 2007. A análise do polimorfismo T869C do gene TGF-beta1 foi realizada pela técnica de reação em cadeia da polimerase (PCR + sistema de amplificação refratária de mutação (ARMS. Os outros polimorfismos, C-509T do gene TGF-beta1, C-159T do gene CD14, C-590T da IL-4, ILe50Val da IL-4Ra e S2 do gene ADAM33, foram detectados por PCR e enzima de restrição. RESULTADOS: Foram incluídos 88 pacientes com asma atópica persistente (27 leves, 23 moderados e 38 graves e 202 indivíduos saudáveis, doadores de sangue. Em relação ao polimorfismo T869C (TGF-beta1, observou-se uma associação entre o genótipo CC e os pacientes com asma grave. Nenhuma associação foi encontrada com os polimorfismos C-509T (TGF-beta1, C-590T (IL4 e S_2 (ADAM33. Quando se comparou a distribuição da freqüência genotípica do polimorfismo C-159T (CD14 na asma grave com o grupo controle, foi observado um resultado significativo com o genótipo TT. Houve associação significativa do genótipo Val/Val (IL-4R com a asma leve. CONCLUSÃO: Nossos resultados indicam que os polimorfismos T869C (TGF-beta1, C-159T (CD14 e Val/Val (IL-4R podem estar envolvidos na modulação da gravidade da asma.OBJECTIVE: To verify the association of transforming growth factor-beta1 (TGF-beta1 (C-509T and T869C, CD14 (C-159T, IL-4 (C-590T, IL-4R (ILe50Val and ADAM33 (S_2 gene polymorphisms with asthma severity in a sample of patients with mild, moderate and severe

  13. Deletion of IL-4 receptor alpha on dendritic cells renders BALB/c mice hypersusceptible to Leishmania major infection.

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    Ramona Hurdayal

    2013-10-01

    Full Text Available In BALB/c mice, susceptibility to infection with the intracellular parasite Leishmania major is driven largely by the development of T helper 2 (Th2 responses and the production of interleukin (IL-4 and IL-13, which share a common receptor subunit, the IL-4 receptor alpha chain (IL-4Rα. While IL-4 is the main inducer of Th2 responses, paradoxically, it has been shown that exogenously administered IL-4 can promote dendritic cell (DC IL-12 production and enhance Th1 development if given early during infection. To further investigate the relevance of biological quantities of IL-4 acting on DCs during in vivo infection, DC specific IL-4Rα deficient (CD11c(creIL-4Rα(-/lox BALB/c mice were generated by gene targeting and site-specific recombination using the cre/loxP system under control of the cd11c locus. DNA, protein, and functional characterization showed abrogated IL-4Rα expression on dendritic cells and alveolar macrophages in CD11c(creIL-4Rα(-/lox mice. Following infection with L. major, CD11c(creIL-4Rα(-/lox mice became hypersusceptible to disease, presenting earlier and increased footpad swelling, necrosis and parasite burdens, upregulated Th2 cytokine responses and increased type 2 antibody production as well as impaired classical activation of macrophages. Hypersusceptibility in CD11c(creIL-4Rα(-/lox mice was accompanied by a striking increase in parasite burdens in peripheral organs such as the spleen, liver, and even the brain. DCs showed increased parasite loads in CD11c(creIL-4Rα(-/lox mice and reduced iNOS production. IL-4Rα-deficient DCs produced reduced IL-12 but increased IL-10 due to impaired DC instruction, with increased mRNA expression of IL-23p19 and activin A, cytokines previously implicated in promoting Th2 responses. Together, these data demonstrate that abrogation of IL-4Rα signaling on DCs is severely detrimental to the host, leading to rapid disease progression, and increased survival of parasites in infected

  14. IL-4 dependent alternatively-activated macrophages have a distinctive in vivo gene expression phenotype

    Directory of Open Access Journals (Sweden)

    Guiliano David

    2002-07-01

    Full Text Available Abstract Background "Alternatively-activated" macrophages are found in Th2-mediated inflammatory settings such as nematode infection and allergic pulmonary inflammation. Due in part to a lack of markers, these cells have not been well characterized in vivo and their function remains unknown. Results We have used murine macrophages elicited by nematode infection (NeMφ as a source of in vivo derived alternatively activated macrophages. Using three distinct yet complementary molecular approaches we have established a gene expression profile of alternatively activated macrophages and identified macrophage genes that are regulated in vivo by IL-4. First, genes abundantly expressed were identified by an expressed sequence tag strategy. Second, an array of 1176 known mouse genes was screened for differential expression between NeMφ from wild type or IL-4 deficient mice. Third, a subtractive library was screened to identify novel IL-4 dependent macrophage genes. Differential expression was confirmed by real time RT-PCR analysis. Conclusions Our data demonstrate that alternatively activated macrophages generated in vivo have a gene expression profile distinct from any macrophage population described to date. Several of the genes we identified, including those most abundantly expressed, have not previously been associated with macrophages and thus this study provides unique new information regarding the phenotype of macrophages found in Th2-mediated, chronic inflammatory settings. Our data also provide additional in vivo evidence for parallels between the inflammatory processes involved in nematode infection and allergy.

  15. Antibacterial properties of the mammalian L-amino acid oxidase IL4I1.

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    Marie-Line Puiffe

    Full Text Available L-amino acid oxidases (LAAO are flavoproteins that catalyze the oxidative deamination of L-amino acids to a keto-acid along with the production of H₂O₂ and ammonia. Interleukin 4 induced gene 1 (IL4I1 is a secreted LAAO expressed by macrophages and dendritic cells stimulated by microbial derived products or interferons, which is endowed with immunoregulatory properties. It is the first LAAO described in mammalian innate immune cells. In this work, we show that this enzyme blocks the in vitro and in vivo growth of Gram negative and Gram positive bacteria. This antibiotic effect is primarily mediated by H₂O₂ production but is amplified by basification of the medium due to the accumulation of ammonia. The depletion of phenylalanine (the primary amino acid catabolized by IL4I1 may also participate in the in vivo inhibition of staphylococci growth. Thus, IL4I1 plays a distinct role compared to other antibacterial enzymes produced by mononuclear phagocytes.

  16. Age-related response of IL-4/Luc/CNS-1 transgenic miceto phthalic anhydrideexposure

    Directory of Open Access Journals (Sweden)

    Sung Ji Eun

    2016-01-01

    Full Text Available Age-related changes are associated with susceptibility to infection, malignancy, autoimmunity, response to vaccination and wound healing. To investigate the relationship of several pathological phenotypes of allergic inflammationto age, alterations in theIL-4 derived luciferase signal and general phenotype biomarkers were measured in young (2-month-old and old (12-month-old IL-4/Luc/CNS-1 transgenic (Tg mice with phthalic anhydride (PA-induced allergic inflammationfor 2 weeks. There was no difference in the ear phenotypes and thickness between young and old mice, although these levels were higher in the PA-treated group thantheacetone-olive oil (AOO-treated group. The luciferase signal was detected in the mesenteric lymph node (ML, thymus and pancreas of both young and old PA-treated mice, but showed a greater increasein old Tg mice (exceptin thethymus. Agreaterincrease inthe epidermal thickness and dermal thickness was measured in old PA-treated mice than young PA-treated mice, while total mast cell number remainedconstant in both groups. Furthermore, the concentration of IgE was greater in young PA-treated mice than in old PA-treated mice,as wasthe expression of VEGF and IL-6. Taken together, theresults of this study showed that an animal’s age is an important factor that must be considered when PA-induced allergic inflammation in IL-4/Luc/CNS-1 Tg mice areinvestigated to screen for allergens and therapeutic compounds.

  17. CD3 antibody and IL-4/IL-4 complex combination therapy inhibits atherosclerosis by augmenting a regulatory immune response%CD3抗体和IL-4/IL-4抗体复合物联合疗法拮抗动脉粥样硬化的免疫机制研究

    Institute of Scientific and Technical Information of China (English)

    齐红双; 薛士鹏; 岳会珠; 段冰杰; 胡兵

    2016-01-01

    目的 采用CD3抗体和IL-4/IL-4抗体复合物联合疗法,增加Tregs/Teffs比例,探讨其对于小鼠动脉粥样硬化的拮抗作用及免疫机制.方法 2014年5-11月采用高胆固醇饮食喂养载脂蛋白E缺陷性小鼠(apoE-/-)40只,随机分为对照组、γ δTCR抗体组、IL-4复合物组及混合组各10只,分别使用空载体、CD3单克隆抗体、IL-4/IL-4抗体免疫复合物、CD3单克隆抗体-IL-4/IL-4抗体免疫复合物干预实验小鼠.检测各组小鼠动脉粥样硬化斑块形态、面积及稳定性、病变部位巨噬细胞及细胞间质含量、淋巴器官内Treg/Teff比例、脾脏单核细胞表型变化情况.计量资料采用方差分析,两两比较采用LSD-t检验,P<0.05为差异有统计学意义.结果 四组脾脏及淋巴结CD4+T细胞/总细胞、CD25+Foxp3+细胞/CD4+细胞、CD25、CD103、类糖诱导TNF受体相关基因/蛋白(GITR)、细胞毒T细胞相关蛋白4(CTLA-4)、体重及血脂水平、Ly6C/单核细胞及CD115(CSF-1受体)水平比较差异均有统计学意义(均P<0.05).混合组脾脏CD25+Foxp3+细胞/CD4+细胞、CD25、CD103、GITR、CTLA-4、甘油三酯、CD115水平均高于对照组,差异均有统计学意义(均P<0.05).混合组淋巴结CD4+T细胞/总细胞、CD25+Foxp3+细胞/CD4+细胞、总胆固醇、低密度脂蛋白胆固醇、Ly6C/单核细胞水平均低于对照组,差异均有统计学意义(均P<0.05).结论 除了降低Teff介导的免疫反应外,增强Treg介导的免疫反应可更为有效的防治动脉粥样硬化,这可能是动脉粥样硬化治疗的新途径.

  18. IL-4 Induces Metallothionein 3- and SLC30A4-Dependent Increase in Intracellular Zn2+ that Promotes Pathogen Persistence in Macrophages

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    Kavitha Subramanian Vignesh

    2016-09-01

    Full Text Available Alternative activation of macrophages promotes wound healing but weakens antimicrobial defenses against intracellular pathogens. The mechanisms that suppress macrophage function to create a favorable environment for pathogen growth remain elusive. We show that interleukin (IL-4 triggers a metallothionein 3 (MT3- and Zn exporter SLC30A4-dependent increase in the labile Zn2+ stores in macrophages and that intracellular pathogens can exploit this increase in Zn to survive. IL-4 regulates this pathway by shuttling extracellular Zn into macrophages and by activating cathepsins that act on MT3 to release bound Zn. We show that IL-4 can modulate Zn homeostasis in both human monocytes and mice. In vivo, MT3 can repress macrophage function in an M2-polarizing environment to promote pathogen persistence. Thus, MT3 and SLC30A4 dictate the size of the labile Zn2+ pool and promote the survival of a prototypical intracellular pathogen in M2 macrophages.

  19. IL-4 receptor-alpha-dependent control of Cryptococcus neoformans in the early phase of pulmonary infection.

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    Andreas Grahnert

    Full Text Available Cryptococcus neoformans is an opportunistic fungal pathogen that causes lung inflammation and meningoencephalitis in immunocompromised people. Previously we showed that mice succumb to intranasal infection by induction of pulmonary interleukin (IL-4Rα-dependent type 2 immune responses, whereas IL-12-dependent type 1 responses confer resistance. In the experiments presented here, IL-4Rα⁻/⁻ mice unexpectedly show decreased fungal control early upon infection with C. neoformans, whereas wild-type mice are able to control fungal growth accompanied by enhanced macrophage and dendritic cell recruitment to the site of infection. Lower pulmonary recruitment of macrophages and dendritic cells in IL-4Rα⁻/⁻ mice is associated with reduced pulmonary expression of CCL2 and CCL20 chemokines. Moreover, IFN-γ and nitric oxide production are diminished in IL-4Rα⁻/⁻ mice compared to wild-type mice. To directly study the potential mechanism(s responsible for reduced production of IFN-γ, conventional dendritic cells were stimulated with C. neoformans in the presence of IL-4 which results in increased IL-12 production and reduced IL-10 production. Together, a beneficial role of early IL-4Rα signaling is demonstrated in pulmonary cryptococcosis, which contrasts with the well-known IL-4Rα-mediated detrimental effects in the late phase.

  20. Serum levels of IL-17, IL-4, and INFγ in Serbian patients with early rheumatoid arthritis

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    Voja Pavlovic

    2014-01-01

    Full Text Available Background: Rheumatoid arthritis (RA is a chronic, systemic, inflammatory disease with autoimmune etiology, characterized by synovial inflammation and destruction of joint cartilage and bone. There are controversial data about the profile of interleukin-17 (IL-17A, interleukin-4 (IL-4, and interferon-gamma (INFγ, indicating in some studies the key role of IL-17, while in others the Th1 cytokines. Materials and Methods: Serum samples of 31 early RA patients were evaluated for erythrocytes sedimentation rate (ESR, rheumatoid factor (RF, C-reactive protein (CRP, anti-cyclic citrullinated peptide antibodies (anti-CCP, and for the tested cytokines (IL-17A, IL-4, and INFγ. Disease activity score (DAS28 calculation was done for all patients. Control serum samples were obtained from 29 healthy volunteers. Results: The levels of tested cytokines were significantly higher (IL-17A, p < 0.001; INFγ, p < 0.001; IL-4, p < 0.01 in patients with early RA, compared to the healthy controls. In early RA patients, a strong correlation of serum IL-17A was found with DAS28, ESR, and CRP. Also, significant negative correlation was found between serum INFγ levels and the DAS28 score, indicating that INFγ may play a key role in maintaining immune homeostasis in patients with RA. Conclusion: The mean serum IL-17A levels in patients with early RA, corresponded with the disease activity and severity. This might highlight the usefulness of the serum IL-17A level in defining the activity and predictive patterns, for aggressive disease therapy, and it might express specific therapeutically targets.

  1. In vivo regulation of the allergic response by the IL-4 receptor alpha chain immunoreceptor tyrosine-based inhibitory motif.

    Science.gov (United States)

    Tachdjian, Raffi; Al Khatib, Shadi; Schwinglshackl, Andreas; Kim, Hong Sook; Chen, Andrew; Blasioli, Julie; Mathias, Clinton; Kim, Hye Young; Umetsu, Dale T; Oettgen, Hans C; Chatila, Talal A

    2010-05-01

    Signaling by IL-4 and IL-13 through the IL-4 receptor alpha chain (IL-4Ralpha) plays a critical role in the pathology of allergic diseases. The IL-4Ralpha is endowed with an immunoreceptor tyrosine-based inhibitory motif (ITIM) centered on tyrosine 709 (Y709) in the cytoplasmic domain that binds a number of regulatory phosphatases. The function of the ITIM in the in vivo regulation of IL-4 receptor signaling remains unknown. We sought to determine the in vivo function of the IL-4Ralpha ITIM by using mice in which the ITIM was inactivated by mutagenesis of the tyrosine Y709 residue into phenylalanine (F709). F709 ITIM mutant mice were derived by means of knock-in mutagenesis. Activation of intracellular signaling cascades by IL-4 and IL-13 was assessed by means of intracellular staining of phosphorylated signaling intermediates and gene expression analysis. In vivo responses to allergic sensitization were assessed by using models of allergic airway inflammation. The F709 mutation increased signal transducer and activator of transcription 6 phosphorylation by IL-4 and, disproportionately, by IL-13. This was associated with exaggerated T(H)2 polarization, enhanced alternative macrophage activation by IL-13, augmented basal and antigen-induced IgE responses, and intensified allergen-induced eosinophilic airway inflammation and hyperreactivity. These results point to a physiologic negative regulatory role for the Y709 ITIM in signaling through IL-4Ralpha, especially by IL-13. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  2. The effects of IL-13 on the expressions of IL-13 receptors and IL-4 receptor in fibroblasts%IL-13对成纤维细胞IL-13受体和IL-4受体表达的影响

    Institute of Scientific and Technical Information of China (English)

    石小玉; 陈厚文; 熊慧玲; 王志刚; 赵林; 李文林

    2012-01-01

    Cytokine interleukin-13 (IL-13) is critical for organ fibrosis. IL-13 receptor alpha 1 (IL-13Rα1) and IL-4 receptor (IL-4R) form a functional IL-13 receptor complex that is thought to mediate most IL-13-induced effects. However, IL-13 receptor alpha 2 (IL-13Rα2), the high affinity receptor for IL-13, is thought to act as a decoy receptor for IL-13. This study aimed to investigate whether the fibrosis-related fibroblast could express IL-13Rα1, IL-4R or IL-13Rα2 and whether IL-13 could regulate the expressions of these receptors. The expressions of IL-13Rα1, IL-4R and IL-13Rα2 mRNA were detected by RT-PCR in human lung fibroblast line HFL-1 and human hepatic stellate cell line LX-2. The luminous intensity of RT-PCR electrophoresis strips was analyzed by gel quantitative software Image Tool 2.0. The expressions of soluble IL-13Rα2, total IL-13Rα1, IL-4R and IL-13Rα2 were measured by ELISA in the supernatant or lysate of HFL-1 cells and LX-2 cells. We found that IL-13 (5 to 100 ng/ml) had no effect on the expressions of IL-13Rα1 and IL-4R in HFL-1 cells and LX-2 cells. IL-13 Rα2 expression of HFL-1 cells was induced in dose-dependent manner under the circumstance of low concentrations of 5 to 20 ng/ml IL-13. However, IL-13Rα2 expression of HFL-1 cells was significantly decreased by using 50 ng/ml of IL-13 as compare with 20 ng/ml of IL-13 group, and could not be induced by using 100 ng/ml of IL-13. On the other hand, IL-13Rα2 expression was not found in LX-2 cells and the stimulation of IL-13 could not induce its expression. These results demonstrate that IL-13 can not up-regulate the expression of IL—13Rα1 and IL-4R, a functional IL-13 receptor complex, in human lung fibroblast line HFL-1 and human hepatic stellate cell line LX-2, indicating that IL-13 can not enlarge their own function by means of increasing IL-13Rα1 and IL-4R expressions. The results also show that certain concentrations of IL-13 can induce the expression of IL-13Rα2, an inhibitory

  3. Study of the correlation between the percentage of iNKT cells and the ratio of IFN-γ/IL-4 in patients with rheumatoid arthritis%类风湿关节炎患者 iNKT 细胞频率与 IFN-γ/IL-4的相关性研究

    Institute of Scientific and Technical Information of China (English)

    孟明; 陈丹; 许鸣华; 侯明辉; 瓮沛杉; 魏芳; 王勇; 陈冬志

    2015-01-01

    目的:检测类风湿关节炎患者外周血中恒定自然杀伤T细胞( invariant nature killer T, iNKT)的频率及功能的变化,分析iNKT细胞频率与血清中IFN-γ/IL-4比值的相关性,进一步明确iNKT细胞在类风湿关节炎( rheumatoid arthritis, RA)发病中的意义。方法收集70例RA患者(并对其中30例患者在缓解期连续跟踪)和40例健康人外周静脉抗凝血并分离单个核细胞( peripheral blood mononuclear,PBMC),采用流式细胞技术(fluorescence-activated cell sorting,FACS)分析样本中iNKT细胞频率;再对PBMC体外培养,FACS动态检测iNKT细胞增殖频率;MILLIPLEX MAP Human Cytokine/Chemokine kit检测相应血清及PBMC培养上清中IFN-γ/IL-4的水平;RT-PCR检测iNKT细胞中IFN-γmRNA与IL-4 mRNA表达水平。结果与健康对照组相比,RA患者iNKT细胞频率及增殖频率显著降低(P<0.05),增殖延迟。治疗后缓解期患者iNKT细胞频率及增殖频率有所恢复,与活动期RA患者比较差异有统计学意义(P<0.05),与健康对照组比较差异无统计学意义(P>0.05);与健康对照组相比,活动期RA患者血清及PBMC培养上清中IFN-γ/IL-4比值升高,差异有统计学意义( P<0.05)。缓解期RA患者血清中IFN-γ/IL-4比值下降,与活动期比较差异有统计学意义( P<0.05),与健康对照组比较,差异无统计学意义(P>0.05);活动期RA患者iNKT细胞中IFN-γmRNA表达升高、IL-4 mRNA表达降低。缓解期RA患者与健康对照组间IFN-γmRNA、IL-4 mRNA表达水平的差异不明显;RA患者外周血中iNKT细胞频率与IFN-γ/IL-4比值呈负相关( P<0.05)。结论RA患者存在iNKT细胞频率低下与功能缺陷。 iNKT细胞参与RA发病过程,且与病情活动性密切相关。%Objective To investigate the alterations of invariant nature killer T( iNKT) cells in peripheral blood samples

  4. Transcription Factors Downstream of IL-4 and TGF-β Signals: Analysis by Quantitative PCR, Western Blot, and Flow Cytometry.

    Science.gov (United States)

    Sugimoto, Atsushi; Kawakami, Ryoji; Mikami, Norihisa

    2017-01-01

    IL-9-producing Th9 cell is a novel Th cell subset involved in type II allergic inflammations such as asthma. Th9 cells can be induced from naïve Th cells in the presence of IL-4 and TGF-β. It is also well established that downstream signals of IL-4 and TGF-β, including STAT6, IRF4, Smad, and PU.1, directly mediate IL-9 production in Th9 cells. In this chapter we describe the methods of flow cytometry, qPCR and western blot analysis to determine the expression or activation of these transcription factors downstream of IL-4 and TGF-β.

  5. IL-4基因大白菜后代的分子检测及遗传分析%Molecular Detection and Genetic Analysis of Chinese Cabbage Progeny with the IL-4

    Institute of Scientific and Technical Information of China (English)

    金晓霞; 高亚; 于丽杰

    2013-01-01

    采用PPT抗性筛选、PCR扩增、PCR-Southern杂交、ELISA、Western杂交等方法,对花粉管通道法介导IL-4基因转化大白菜的后代进行了分子生物学检测,同时结合统计分析手段研究了IL-4基因在转基因大白菜后代中的遗传规律.结果表明:(1)PPT抗性的转基因大白菜,T4代植株PPT抗性的阳性率为33.43%,IL-4基因PCR扩增的阳性率为1.39%.IL-4的分离情况不符合孟德尔分离定律.(2)对T4代5个株系的14个PCR阳性株进行ELISA检测,其中有7份样品为阳性,IL-4表达量约为326.87 ~ 1233.13 ng/g FW,同一株系内各株间IL-4的表达量差异显著.(3) Western杂交进一步证实IL-4在转基因大白菜后代中能正常表达.PCR-southern杂交表明IL-4基因已整合到大白菜基因组中,且在转基因后代植株中仍然存在.%IL-4 gene transformation mediated by pollen-tube pathway method of Chinese cabbage for molecular detection of descendants using PPT resistance screening,PCR amplification,PCR-Southern hybrid,ELISA,Western hybrid methods,combined with statistical analysis study IL-4 inheritance of genes in transgenic Chinese cabbage in future generations.Results indicated that:(1) PPT resistance in transgenic Chinese cabbage,PPT resistance positive rates of T4 generation was 33.43%,the positive rate of PCR amplification of IL-4 gene was 1.39%.IL-4 separation plant does not meet Mendel' s law of segregation.(2) ELISA test on 14 ones of PCR-positive strains of 5 strains in the T4 generation,7 samples of which are positive,IL-4 expression was about 326.87 ~ 1233.13 ng/g FW,the ones of IL-4 expression within the same strains significance of difference.(3) Western confirmed IL-4 in transgenic Chinese cabbage hybrid offspring in the regular expression.It indicated that IL-4 gene has been incorporated into the Chinese cabbage in the genome with PCR-southern hybrid,and that gene still exists in transgenic plants' future generations.

  6. Allergy Vaccines Using a Mycobacterium-Secreted Antigen, Ag85B, and an IL-4 Antagonist.

    Science.gov (United States)

    Tsujimura, Yusuke; Yasutomi, Yasuhiro

    2016-01-01

    In recent decades, the prevalence of allergic diseases, including bronchial asthma, airway hypersensitivity, hay fever, and atopic dermatitis, has been increasing in the industrialized world, and effective treatments probably require manipulating the inflammatory response to pathogenic allergens. T helper (Th) 2 cells are thought to play a crucial role in the initiation, progression, and persistence of allergic responses in association with production of interleukin (IL)-4, IL-5, and IL-13. Therefore, a strategy of a shift from Th2- to Th1-type immune response may be valuable in the prophylaxis and management of allergic diseases. It is also necessary to develop prophylactic and therapeutic treatment that induces homeostatic functions in the multifaceted allergic environment, because various factors including innate and adaptive immunity, mucosal immune response, and functional and structural maintenance of local tissue might be involved in the pathogenesis of allergic disorders. We review herein recent findings related to the curative effect for mouse models of asthma and atopic dermatitis using DNA-, virus-, and protein-based vaccines of a Mycobacterium secretion antigen, Ag85B, and a plasmid encoding cDNA of antagonistic IL-4 mutant.

  7. 青霉素过敏反应与IL-4、IL-13、IFN-γ

    Institute of Scientific and Technical Information of China (English)

    乔海灵; 张跃文; 杨静; 刘久红

    2003-01-01

    @@ 目的:探讨青霉素类抗生素过敏与IL-4、IL-13、IFN-γ之间的关系.方法:采用ELISA法检测了145例过敏病人和62例正常人血清中的IL-4、IL-13和IFN-γ浓度;采用RAST法检测了过敏病人和正常人血清中的8种特异性IgE抗体(BPO-PLL、PVO-PLL、APO-PLL、AXO-PLL、BPA-PLL、 PVA-PLL、APA-PLL、AXA-PLL).结果:特异性IgE抗体阳性的青霉素过敏病人组IL-4、IL-13、IFN-γ血清浓度显著高于正常组(P<0.01);特异性IgE抗体阴性的青霉素过敏病人组IL-4、IFN-γ浓度显著低于正常组(P<0.01);IL-4与IL-13的正相关有显著性(P<0.01);IL-4和IL-13与多种特异性抗体之间的正相关有显著性(P<0.01);随着病人青霉素特异性IgE抗体阳性种类的增多,血清中IL-4、IL-13水平显著升高(P<0.01).结论:青霉素过敏反应中,特异性抗体阳性类型的过敏反应与IL-4、IL-13、IFN-γ升高有关;特异性抗体阴性类型的过敏反应与IL-4、IFN-γ降低有关;IL-4、IL-13可能与青霉素特异性IgE抗体的产生有关;IL-4、IL-13的升高可能会增加病人对更多抗原的敏感性.

  8. Expression of IL-4 and IL-13 predicts recurrence and survival in localized clear-cell renal cell carcinoma.

    Science.gov (United States)

    Chang, Yuan; Xu, Le; An, Huimin; Fu, Qiang; Chen, Lian; Lin, Zongming; Xu, Jiejie

    2015-01-01

    Interleukin-4 (IL-4) and IL-13 are anti-inflammatory and immunoregulatory cytokines that can influence cancer-directed immunosurveillance. However, they are not evaluated as biomarkers for ccRCC outcomes. The aim of this study was to investigate the prognostic value of tumor-derived IL-4 and IL-13 in patients with localized ccRCC after surgery. Our study comprised 194 consecutive patients with localized ccRCC undergoing nephrectomy in a single center. Clinical characteristics, recurrence-free survival (RFS) and overall survival (OS) were recorded. We assessed IL-4 and IL-13 expression as continuous variables and dichotomized as low versus high by immunohistochemistry. For associations with RFS and OS, we used the Kaplan-Meier method and Cox regression models. Concordance index was calculated for predictive accuracy. We found that high expression levels of IL-4 and IL-13 were associated with increased recurrence (P IL-13 expression (IL-4/IL-13 signature) was an independent prognostic factor for RFS and OS (P = 0.009 and P = 0.016, respectively). When applied to UISS score, IL-4/IL-13 signature improved the predictive accuracy. Notably, this improvement in prediction was mainly observed in patients with low-risk disease. To conclude, IL-4/IL-13 signature is an independent predictor of outcomes in patients with localized ccRCC, and the prognostic value is more prominent among patients with low-risk disease. Evaluation of IL-4 and IL-13 expression provides the opportunity to optimize postsurgical management and develop novel targeted therapies for ccRCC patients.

  9. The Effect of IL-4 Gene Polymorphisms on Cytokine Production in Patients with Chronic Periodontitis and in Healthy Controls

    Directory of Open Access Journals (Sweden)

    Jirina Bartova

    2014-01-01

    Full Text Available Chronic periodontitis (CP is an inflammatory disease of the teeth-supporting tissues in which genetic predisposition, dental plaque bacteria, and immune mechanisms all play important roles. The aim of this study was to evaluate the occurrence of IL-4 gene polymorphisms in chronic periodontitis and to investigate the association between polymorphisms and cytokines production after bacterial stimulation. Sixty-two subjects (47 CP patients and 15 healthy controls with detected two polymorphisms in the IL-4 gene (-590C/T and intron 3 VNTR were examined. Production of cytokines (IL-1α, IL-1β, IL-4, IL-5, IL-6, IL-10, IL-17, TNFα, INFγ, and VEGF was studied after in vitro stimulation of isolated peripheral blood by mitogens (Pokeweed mitogen, Concanavalin A, dental plaque bacteria (Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Porphyromonas gingivalis, and Prevotella intermedia, and Heat Shock Protein (HSP 70 by the Luminex multiplex cytokine analysis system. The results were correlated with IL-4 genotypes in patients with CP and healthy controls. The mononuclear cells isolated from peripheral blood of CP patients with selected IL-4 polymorphisms significantly altered the production of IFNγ, IL-10, IL-1β, IL-1α, TNFα, and IL-6 after stimulation by HSP 70 or selected bacteria (from P<0.001 to P<0.05. IL-4 gene polymorphisms may influence the function of mononuclear cells to produce not only interleukin-4 but also other cytokines, especially in patients with CP.

  10. Il-4 and IL-13, but not IL-10, protect human synoviocytes from apoptosis.

    NARCIS (Netherlands)

    Relic, B.; Guicheux, J.; Mezin, F.; Lubberts, G.J.H.; Togninalli, D.; Garcia, I.; Berg, W.B. van den; Guerne, P.A.

    2001-01-01

    Interleukin-4, which has been contemplated for the treatment of rheumatoid arthritis and/or osteoarthritis because of its anticatabolic properties, has also been shown to modulate apoptosis. Because inadequate apoptosis is thought to contribute to synovial hyperplasia, we have investigated the abili

  11. 中药"凤香洗液"对伴HPV感染的CIN患者宫颈局部IL-2和IL-4的影响%Effects of traditional Chinese medicine"Fengxiang Lotion"on local cervical IL-2 and IL-4 in patients of cervical intraepithelial neoplasia with HPV infection

    Institute of Scientific and Technical Information of China (English)

    李小宁; 贺丰杰; 吉喆

    2015-01-01

    Objective To observe the effects of traditional Chinese medical compound"Fengxiang Lotion"on the local vaginal immune state for patients of cervical intraepithelial neoplasia (CIN) with human papillomavirus (HPV) infection.Methods Sixty patients with high risk HPV infection diagnosed with cervical biopsy using colpos-copy in the Affiliated Hospital of Shaanxi University of Chinese Medicine and Xi'an XD Group Hospital from July 2013 to February 2015 were selected in the study,which were divided into CINⅠand CINⅡgroup (n=30 each).Thirty healthy women coming for medical examination during the same period served as the control group.CINⅠgroup received Fengxiang Lotion for treatment,while the other two groups not.The levels of interleukin (IL)-2 and IL-4 in cervical-vaginal lavage solution,which were synthesized by type 1 and type 2 helper T cells respective-ly,were tested by ELISA.Results (1) IL-2 levels of CINⅠgroup and CINⅡgroup were significantly lower than that of the control group (P<0.01),while IL-4 levels of CINⅠgroup and CINⅡ group were significantly higher (P<0.05).The ratios of IL-2 to IL-4 in CINⅠgroup and CINⅡgroup were significantly lower than that of the con-trol group (P<0.05).What's more,all these changes was more significant in CINⅡgroup than CINⅠgroup (P<0.05).(2) In CINⅠgroup,the IL-2 level increased significantly after medication (P<0.05),while IL-4 decreased significantly (P<0.05),with the ratio of IL-2 to IL-4 increased significantly (P<0.01).Conclusion The IL-2 lev-els and IL-2/IL-4 ratio in CIN patients with HPV decreased,while IL-4 increased.These changes were consistent with the severity of CIN."Fengxiang Lotion"may block the progression of CIN through regulating the balance of Th1 and Th2.%目的 观察中药"凤香洗液"对伴有HPV感染的CINⅠ、CINⅡ患者阴道局部免疫状态的影响及治疗效果.方法 选取2013年7月至2015年2月于陕西中医学院附属医院、西安西电集团医院门诊就

  12. 关节炎大鼠模型血清中IL-4、IL-10表达的检测%Detection on Expression of IL-4 and IL-10 in Adjuvant Arthritis Rats Models

    Institute of Scientific and Technical Information of China (English)

    范雪亮; 肖金鱼

    2011-01-01

    Objeetive:To detect the expressions including IL-4 and IL-10 in adjuvant arthritis (AA) rats models. Methods:After the AA rats models were established,the IL-4 and the IL-10 were determined by ELJSA method. Results:Compared with the control group,the IL -A and the IL-10 were decreased obviously. Conclusion;That there are small amounts of IL-4 and IL-10 is indicating that IL-4 and IL-10 are inhibit in the RA onset period.%目的 检测白细胞介素-4(IL-4)、白细胞介素-10(IL-10)在佐剂性关节炎(AA)大鼠模型血清中的水平。方法建立AA大鼠模型,根据X线片及组织病理学的特点证实造模成功。用ELISA法检测AA大鼠模型血清中炎性细胞因子IL-4、IL-10的水平。结果与对照组大鼠比较,模型组大鼠血清中IL-4、IL-10水平明显降低。结论模型组大鼠血清中含有少量的lL-1、L-10,提示在类风湿关节炎的发病过程中IL-1、IL-10的分泌受到了抑制。

  13. GATA3 expression is decreased in psoriasis and during epidermal regeneration; induction by narrow-band UVB and IL-4.

    Science.gov (United States)

    Rácz, Emoke; Kurek, Dorota; Kant, Marius; Baerveldt, Ewout M; Florencia, Edwin; Mourits, Sabine; de Ridder, Dick; Laman, Jon D; van der Fits, Leslie; Prens, Errol P

    2011-01-01

    Psoriasis is characterized by hyperproliferation of keratinocytes and by infiltration of activated Th1 and Th17 cells in the (epi)dermis. By expression microarray, we previously found the GATA3 transcription factor significantly downregulated in lesional psoriatic skin. Since GATA3 serves as a key switch in both epidermal and T helper cell differentiation, we investigated its function in psoriasis. Because psoriatic skin inflammation shares many characteristics of epidermal regeneration during wound healing, we also studied GATA3 expression under such conditions.Psoriatic lesional skin showed decreased GATA3 mRNA and protein expression compared to non-lesional skin. GATA3 expression was also markedly decreased in inflamed skin of mice with a psoriasiform dermatitis induced with imiquimod. Tape-stripping of non-lesional skin of patients with psoriasis, a standardized psoriasis-triggering and skin regeneration-inducing technique, reduced the expression of GATA3. In wounded skin of mice, low GATA3 mRNA and protein expression was detected. Taken together, GATA3 expression is downregulated under regenerative and inflammatory hyperproliferative skin conditions. GATA3 expression could be re-induced by successful narrow-band UVB treatment of both human psoriasis and imiquimod-induced psoriasiform dermatitis in mice. The prototypic Th2 cytokine IL-4 was the only cytokine capable of inducing GATA3 in skin explants from healthy donors. Based on these findings we argue that GATA3 serves as a key regulator in psoriatic inflammation, keratinocyte hyperproliferation and skin barrier dysfunction.

  14. IL-2, IL-4, IFN-γ or TNF-α enhances BAFF-stimulated cell viability and survival by activating Erk1/2 and S6K1 pathways in neoplastic B-lymphoid cells.

    Science.gov (United States)

    Gui, Lin; Zeng, Qingyu; Xu, Zhigang; Zhang, Hai; Qin, Shanshan; Liu, Chunxiao; Xu, Chong; Qian, Zhou; Zhang, Shuangquan; Huang, Shile; Chen, Long

    2016-08-01

    B-cell activating factor of the TNF family (BAFF) has been documented to act as a critical factor in the development of aggressive B lymphocytes and autoimmune diseases. However, the effect of various cytokines on BAFF-elicited neoplastic B-lymphoid cells is not known. In this study, we exhibited that administration of human soluble BAFF (hsBAFF), IL-2, IL-4, IFN-γ, or TNF-α alone increased cell viability and survival in Raji cells concentration-dependently, yet a more robust viability/survival was seen in the cells co-treatment of IL-2, IL-4, IFN-γ, or TNF-α with hsBAFF, respectively. Further research revealed that both Erk1/2 and S6K1 signaling pathways were essential for IL-2, IL-4, IFN-γ, or TNF-α enhancement of the viability/survival in the hsBAFF-stimulated cells, as inhibition of Erk1/2 with U0126 or down-regulation of Erk1/2, or blockage of S6K1 with rapamycin or silencing S6K1, or silencing S6K1/Erk1/2, respectively, reduced the cell viability/survival in the cells treated with/without hsBAFF±IL-2, IL-4, IFN-γ, or TNF-α. These findings indicate that IL-2, IL-4, IFN-γ or TNF-α enhances BAFF-stimulated cell viability/survival by activating Erk1/2 and S6K1 signaling in neoplastic B-lymphoid cells. Our data suggest that modulation of IL-2, IL-4, IFN-γ and/or TNF-α levels, or inhibitors of Erk1/2 or S6K1 may be a new approach to prevent BAFF-induced aggressive B-cell malignancies.

  15. BALB/c mice deficient in CD4 T cell IL-4Rα expression control Leishmania mexicana Load although female but not male mice develop a healer phenotype.

    Directory of Open Access Journals (Sweden)

    Karen J Bryson

    2011-01-01

    Full Text Available Immunologically intact BALB/c mice infected with Leishmania mexicana develop non-healing progressively growing lesions associated with a biased Th2 response while similarly infected IL-4Rα-deficient mice fail to develop lesions and develop a robust Th1 response. In order to determine the functional target(s for IL-4/IL-13 inducing non-healing disease, the course of L. mexicana infection was monitored in mice lacking IL-4Rα expression in specific cellular compartments. A deficiency of IL-4Rα expression on macrophages/neutrophils (in LysM(creIL-4Rα(-/lox animals had minimal effect on the outcome of L. mexicana infection compared with control (IL-4Rα(-/flox mice. In contrast, CD4(+ T cell specific (Lck(creIL-4Rα(-/lox IL-4Rα(-/- mice infected with L. mexicana developed small lesions, which subsequently healed in female mice, but persisted in adult male mice. While a strong Th1 response was manifest in both male and female CD4(+ T cell specific IL-4Rα(-/- mice infected with L. mexicana, induction of IL-4 was manifest in males but not females, independently of CD4(+ T cell IL-4 responsiveness. Similar results were obtained using pan-T cell specific (iLck(creIL-4Rα(-/lox IL-4Rα(-/- mice. Collectively these data demonstrate that upon infection with L. mexicana, initial lesion growth in BALB/c mice is dependent on non-T cell population(s responsive to IL-4/IL-13 while progressive infection is dependent on CD4(+ T cells responsive to IL-4.

  16. The Serum Levels of IL-4, IL-5 and IFN-γ in Skin Allergy- and Measles- Induced Exanthema

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    Arshi Saba

    2009-10-01

    Full Text Available Macular or maculopapular skin reactions are frequent events in skin allergies as well as in viral infections. Clinically, the differentiation may be difficult in the absence of a clear relationship with drug intake or in the failure to detect measles virus-specific antibodies. Studies on drug-specific T cell lines and T cell clones isolated from skin-allergy patients have suggested that these cells may represent a significant source of IL-4 and IL-5. On the other hand, viral infections are frequently associated with elevated IFN-γ levels. Determination of serum cytokine levels helps to differentiate between skin allergies and virally induced skin eruptions. Forty patients suffering from skin allergy and 40 patients with measles infection entered the study. Serum IL-4, IL-5 and IFN-γ levels were determined by ELISA assay for skin-allergy and measles patients. In 37/40 patients with skin allergy, IL-4 was elevated and in 6/40 patients with skin allergy IFN-γ was measurable. In 29/40 patients with measles infection, IFN-γ serum levels were elevated and 32/40 patients with measles had elevated IL-4 levels. IL-5 was increased in 32/40 patients with measles infection and in 34/40 patients with skin allergy. These data underline the distinct pathogenesis of these morphologically similar exanthemas and suggest that a combined analysis of IL-4, IL-5, and IFN-γ might help differentiate skin eruptions.

  17. Expression of rabbit IL-4 by recombinant myxoma viruses enhances virulence and overcomes genetic resistance to myxomatosis.

    Science.gov (United States)

    Kerr, P J; Perkins, H D; Inglis, B; Stagg, R; McLaughlin, E; Collins, S V; Van Leeuwen, B H

    2004-06-20

    Rabbit IL-4 was expressed in the virulent standard laboratory strain (SLS) and the attenuated Uriarra (Ur) strain of myxoma virus with the aim of creating a Th2 cytokine environment and inhibiting the development of an antiviral cell-mediated response to myxomatosis in infected rabbits. This allowed testing of a model for genetic resistance to myxomatosis in wild rabbits that have undergone 50 years of natural selection for resistance to myxomatosis. Expression of IL-4 significantly enhanced virulence of both virulent and attenuated virus strains in susceptible (laboratory) and resistant (wild) rabbits. SLS-IL-4 completely overcame genetic resistance in wild rabbits. The pathogenesis of SLS-IL-4 was compared in susceptible and resistant rabbits. The results support a model for resistance to myxomatosis of an enhanced innate immune response controlling virus replication and allowing an effective antiviral cell-mediated immune response to develop in resistant rabbits. Expression of IL-4 did not overcome immunity to myxomatosis induced by immunization.

  18. Expression of TSLP and Downstream Molecules IL-4, IL-5, and IL-13 on the Eye Surface of Patients with Various Types of Allergic Conjunctivitis

    Directory of Open Access Journals (Sweden)

    Xiaofen Zheng

    2016-01-01

    Full Text Available Background. The pathogenesis of allergic conjunctivitis has not been clearly established. Moreover, previous studies fail to consider human models of allergic conjunctivitis. This study investigated the expression of thymic stromal lymphopoiet in TSLP and its downstream molecules in conjunctival scrappings and tear. Methods. This cross-sectional study compares patients with vernal keratoconjunctivitis (VKC, seasonal allergic conjunctivitis (SAC, and perennial allergic conjunctivitis (PAC with normal controls. There are 80 people recorded in Shanxi Eye Hospital. Increasingly, 20 are with VKC, 20 are with SAC, 20 are with PAC, and the remaining 20 are normal controls. Conjunctiva were harvested for total RNA extraction and gene expression by real-time polymerase chain reaction. Epithelial cells were collected to make pathological sections for immunohistochemical staining. Human tears were evaluated by Luminex microbead assay. A P value less than 0.05 from Dunnett’s post hoc test in SPSS means a statistical significant distinction. Results. Positive expression in conjunctival cells of patients with allergic conjunctivitis. The expression of TSLP and IL-4, IL-5, and IL-13 mRNA shows a statistically significant difference (P<0.05. TSLP and IL-4, IL-5, and IL-13 concentrations show a statistically significant difference (P<0.01. Conclusions. This study suggests that TSLP and downstream molecules are expressed in patients with various types of allergic conjunctivitis.

  19. Microglia activated by IL-4 or IFN-gamma differentially induce neurogenesis and oligodendrogenesis from adult stem/progenitor cells.

    Science.gov (United States)

    Butovsky, Oleg; Ziv, Yaniv; Schwartz, Adi; Landa, Gennady; Talpalar, Adolfo E; Pluchino, Stefano; Martino, Gianvito; Schwartz, Michal

    2006-01-01

    Cell renewal in the adult central nervous system (CNS) is limited, and is blocked in inflammatory brain conditions. We show that both neurogenesis and oligodendrogenesis of adult neural progenitor cells in mice are blocked by inflammation-associated (endotoxin-activated) microglia, but induced by microglia activated by cytokines (IL-4 or low level of IFN-gamma) associated with T-helper cells. Blockage was correlated with up-regulation of microglial production of tumor necrosis factor-alpha. The effect induced by IL-4-activated microglia was mediated, at least in part, by insulin-like growth factor-I. The IL-4-activated microglia showed a bias towards oligodendrogenesis whereas the IFN-gamma-activated microglia showed a bias towards neurogenesis. It thus appears that microglial phenotype critically affects their ability to support or impair cell renewal from adult stem cell.

  20. IL-1, IL-4 production and IgE levels in acute and chronic fasciolosis before and after triclabendazole treatment.

    Science.gov (United States)

    Allam, A F; Osman, M M; el-Sayed, M H; Demian, S R

    2000-12-01

    IL-1 generation by mononuclear phagocytes, IL-4 production by Th2 lymphocytes and IgE levels in serum were measured in eight patients with acute fasciolosis and seven patients in the chronic stage of the disease before and after triclabendazole treatment. Results were compared with those of a control group of ten individuals. The monocytes and lymphocytes from patients with acute and chronic fasciolosis produced significantly lower levels of IL-1 and IL-4 respectively, particularly in the chronic phase of the disease, as compared to the control. A significant increase in IgE level in both acute and chronic fasciolosis was observed. The level was significantly higher in acute as compared to chronic cases. After treatment with triclabendazole IL-1, IL-4 and IgE levels moved towards the control indicating obvious improvement in the immunological responses of the patients.

  1. Evaluation of IL-4, IL-17, and IFN-γ Levels in PatientsWith Breast Cancer

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    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.

  2. Abrogation of IL-4 receptor-α-dependent alternatively activated macrophages is sufficient to confer resistance against pulmonary cryptococcosis despite an ongoing T(h)2 response.

    Science.gov (United States)

    Müller, Uwe; Stenzel, Werner; Piehler, Daniel; Grahnert, Andreas; Protschka, Martina; Köhler, Gabriele; Frey, Oliver; Held, Josephin; Richter, Tina; Eschke, Maria; Kamradt, Thomas; Brombacher, Frank; Alber, Gottfried

    2013-08-01

    In the murine model of pulmonary infection with Cryptococcus neoformans, IL-4 receptor α (IL-4Rα)-dependent polyfunctional T(h)2 cells induce disease progression associated with alternative activation of lung macrophages. To characterize the effector role of IL-4Rα-dependent alternatively activated macrophages (aaMph), we intra-nasally infected mice with genetically ablated IL-4Rα expression on macrophages (LysM(Cre)IL-4Rα(-/lox) mice) and IL-4Rα(-/lox) littermates. LysM(Cre)IL-4Rα(-/lox) mice were significantly more resistant to pulmonary cryptococcosis with higher survival rates and lower lung burden than non-deficient heterozygous littermates. Infected LysM(Cre)IL-4Rα(-/lox) mice had reduced but detectable numbers of aaMph expressing arginase-1, chitinase-like enzyme (YM1) and CD206. Similar pulmonary expression of inducible nitric oxide synthase was found in LysM(Cre)IL-4Rα(-/lox) and IL-4Rα(-/lox) control mice, but macrophages from LysM(Cre)IL-4Rα(-/lox) mice showed a higher potential to produce nitric oxide. In contrast to the differences in the macrophage phenotype, pulmonary T(h)2 responses were similar in infected LysM(Cre)IL-4Rα(-/lox) and IL-4Rα(-/lox) mice with each mouse strain harboring polyfunctional T(h)2 cells. Consistently, type 2 pulmonary allergic inflammation associated with eosinophil recruitment and epithelial mucus production was present in lungs of both LysM(Cre)IL-4Rα(-/lox) and IL-4Rα(-/lox) mice. Our results demonstrate that, despite residual IL-4Rα-independent alternative macrophage activation and ongoing T(h)2-dependent allergic inflammation, abrogation of IL-4Rα-dependent aaMph is sufficient to confer resistance in pulmonary cryptococcosis. This is even evident on a relatively resistant heterozygous IL-4Rα(+/-) background indicating a key contribution of macrophage IL-4Rα expression to susceptibility in allergic bronchopulmonary mycosis.

  3. Retrovirus-mediated delivery of an IL-4 receptor antagonist inhibits allergic responses in a murine model of asthma

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    This work reports the investigation of the effect of airway IL-4RA gene transfer by a recombinant retroviral vector on airway inflammation and airway responsiveness in asthmatic mice. The retrovirus-mediated delivery of IL-4RA to the airways of mice inhibited elevations of airway responsiveness and the development of allergic inflammation in asthmatic mice, and regulated the Th1/Th2 balance in OVA-sensitized and -challenged mouse models. This suggests that gene therapy is a therapeutic option for treating and controlling chronic airway inflammation and asthma symptoms.

  4. CLINICAL FEATURES AND SIGNIFICANCE OF CYTOKINE IL-4 IN CHILDREN WITH DENGUE AT A TERTIARY CARE CENTRE

    Directory of Open Access Journals (Sweden)

    Rakesh Manoharan

    2016-12-01

    Full Text Available BACKGROUND Dengue is a mosquito borne viral infection in tropical and subtropical regions caused by one of the four serotypes of dengue viruses (DENV1-DENV4. The consequences of DENV infection range from asymptomatic condition Dengue Fever (DF or severe forms such as Dengue Haemorrhagic Fever (DHF and Dengue Shock Syndrome (DSS. The host immune responses have been considered as the major factor responsible for dengue pathogenesis. Endothelial activation markers such as expression of adhesion molecules and receptors have been found to serve as biomarkers of severe dengue disease. In this study, the cytokine IL-4 is reviewed for its utility as potential biomarker of severe dengue disease. MATERIALS AND METHODS 120 children of paediatric age group from 1 month till 18 years of age with fever for more than 5 days with either dengue NS1 antigen or dengue IgM positive were included. 30 children who were admitted for noninfectious disease (e.g. surgery without fever, any systemic illness and preexisting illness (tuberculosis, asthma in SRMC and RI were taken as controls. Cases were classified as uncomplicated dengue (dengue without warning signs and complicated dengue (dengue with warning signs and severe dengue. Clinical features and IL-4 (ELISA kit were analysed and compared among the study population and statistical analysis done for the obtained data. RESULTS Analysis of clinical features among the study groups revealed children with complicated dengue had persistent vomiting (95%, abdominal pain (80%, decreased urine output (50%, bleeding manifestations (83.3%, hepatomegaly (70%, haemoconcentration with concurrent thrombocytopenia (93.3%, altered coagulation profile (28.3%, ICU stay (54.7%, leucocytosis (15%, leucopenia (66.6% and normal leucocytes (18.4%. Analysis of IL-4 levels revealed children with complicated dengue showed >6 fold elevation in IL-4 levels (p=0.003. Mean IL-4 levels in complicated dengue group was also statistically

  5. Chromosome 5q candidate genes in coeliac disease: genetic variation at IL4, IL5, IL9, IL13, IL17B and NR3C1.

    Science.gov (United States)

    Ryan, A W; Thornton, J M; Brophy, K; Daly, J S; McLoughlin, R M; O'Morain, C; Abuzakouk, M; Kennedy, N P; Stevens, F M; Feighery, C; Kelleher, D; McManus, R

    2005-02-01

    Genetic predisposition to coeliac disease (CD) is determined primarily by alleles at the HLA-DQB locus, and evidence exists implicating other major histocompatibility complex-linked genes (6p21) and the CTLA4 locus on chromosome 2q33. In addition, extensive family studies have provided strong, reproducible evidence for a susceptibility locus on chromosome 5q (CELIAC2). However, the gene responsible has not been identified. We have assayed genetic variation at the IL4, IL5, IL9, IL13, IL17B and NR3C1 (GR) loci, all of which are present on chromosome 5q and have potential or demonstrated involvement in autoimmune and/or inflammatory disease, in a sample of 409 CD cases and 355 controls. Thirteen single nucleotide polymorphisms were chosen on the basis of functional relevance, prior disease association and, where possible, prior knowledge of the haplotype variation present in European populations. There were no statistically significant allele or haplotype frequency differences between cases and controls. Therefore, these results provide no evidence that these loci are associated with CD in this sample population.

  6. IL-4 and IL-13 induce protection from complement and melittin in endothelial cells despite initial loss of cytoplasmic proteins: membrane resealing impairs quantifying cytotoxicity with the lactate dehydrogenase permeability assay.

    Science.gov (United States)

    Benson, Barbara A; Vercellotti, Gregory M; Dalmasso, Agustin P

    2015-01-01

    Endothelial cell activation and injury by the terminal pathway of complement is important in various pathobiological processes, including xenograft rejection. Protection against injury by human complement can be induced in porcine endothelial cells (ECs) with IL-4 and IL-13 through metabolic activation. However, despite this resistance, the complement-treated ECs were found to lose membrane permeability control assessed with the small molecule calcein. Therefore, to define the apparent discrepancy of permeability changes vis-à-vis the protection from killing, we now investigated whether IL-4 and IL-13 influence the release of the large cytoplasmic protein lactate dehydrogenase (LDH) in ECs incubated with complement or the pore-forming protein melittin. Primary cultures of ECs were pre-treated with IL-4 or IL-13 and then incubated with human serum as source of antibody and complement or melittin. Cell death was assessed using neutral red. Membrane permeability was quantitated measuring LDH release. We found that IL-4-/IL-13-induced protection of ECs from killing by complement or melittin despite loss of LDH in amounts similar to control ECs. However, the cytokine-treated ECs that were protected from killing rapidly regained effective control of membrane permeability. Moreover, the viability of the protected ECs was maintained for at least 2 days. We conclude that the protection induced by IL-4/IL-13 in ECs against lethal attack by complement or melittin is effective and durable despite severe initial impairment of membrane permeability. The metabolic changes responsible for protection allow the cells to repair the membrane injury caused by complement or melittin.

  7. Diseases associated with leaky hemichannels

    Science.gov (United States)

    Retamal, Mauricio A.; Reyes, Edison P.; García, Isaac E.; Pinto, Bernardo; Martínez, Agustín D.; González, Carlos

    2015-01-01

    Hemichannels (HCs) and gap junction channels (GJCs) formed by protein subunits called connexins (Cxs) are major pathways for intercellular communication. While HCs connect the intracellular compartment with the extracellular milieu, GJCs allow the interchange of molecules between cytoplasm of two contacting cells. Under physiological conditions, HCs are mostly closed, but they can open under certain stimuli allowing the release of autocrine and paracrine molecules. Moreover, some pathological conditions, like ischemia or other inflammation conditions, significantly increase HCs activity. In addition, some mutations in Cx genes associated with human diseases, such as deafness or cataracts, lead to the formation of more active HCs or “leaky HCs.” In this article we will revise cellular and molecular mechanisms underlying the appearance of leaky HCs, and the consequences of their expression in different cellular systems and animal models, in seeking a common pattern or pathological mechanism of disease. PMID:26283912

  8. Diseases associated with leaky hemichannels.

    Directory of Open Access Journals (Sweden)

    Mauricio Antonio Retamal

    2015-07-01

    Full Text Available Hemichannels (HCs and gap junction channels (GJCs formed by protein subunits called connexins (Cxs are major pathways for intercellular communication. While HCs connect the intracellular compartment with the extracellular milieu, GJCs allow the interchange of molecules between cytoplasm of two contacting cells. Under physiological conditions, HCs are mostly closed, but they can open under certain stimuli allowing the release of autocrine and paracrine molecules. Moreover, some pathological conditions, like ischemia or other inflammation conditions, significantly increase HCs activity. In addition, some mutations in Cx genes associated with human diseases, such as deafness or cataracts, lead to the formation of more active HCs or leaky HCs. In this article we will revise cellular and molecular mechanisms underlying the appearance of leaky HCs, and the consequences of their expression in different cellular systems and animal models, in seeking a common pattern or pathological mechanism of disease.

  9. Acute Respiratory Disease Associated with Mannheimia ...

    African Journals Online (AJOL)

    Acute Respiratory Disease Associated with Mannheimia Haemolytica ... to the Veterinary Teaching Hospital (VTH), University of Agriculture, Abeokuta, Nigeria. Mannheimia spp was isolated from the nasal swab and lymph node and lung ...

  10. Enteric nematodes and the path to up-regulation of type 2 cytokines IL-4 and IL-13.

    Science.gov (United States)

    Shea-Donohue, Terez; Sun, Rex; Bohl, Jennifer A; McLean, Leon P; Zhao, Aiping

    2015-09-01

    Protective immunity against enteric parasitic nematodes is dependent on IL-4, IL-13 activation of their exclusive transcription factor STAT6. The precise pathways by which enteric parasitic nematodes are recognized by the host is unclear, but elimination of this important interaction in developed nations is thought to contribute to the dysregulated immune responses that are a characteristic of autoimmune diseases. Nematode-derived products are involved in evading host defenses to promote their life cycle leading to modulation of host immune responses. Host protective immunity has adapted to enteric parasitic nematode infection by elaboration of mucins, increasing intraluminal fluid to control access to the surface epithelium, increasing cell turnover to maintain an effective barrier to their invasion, initiating immune responses through activation of resident immune cells, and recruitment of additional immune cells to release immune mediators that help orchestrate these responses. Both the immune and functional outcomes depend largely on IL-4/IL-13 signaling through STAT6, with a dominant role for IL-13 working through the type 2 IL-4 receptor (IL-4R). The recent observation that enteric nematode infection prevents the onset of a number of experimental models of IBD, diabetes, and several extraintestinal autoimmune diseases including multiple sclerosis has generated considerable interest in the identification of worm/egg products involved in the generation and maintenance of Th2 cytokines that may mediate the beneficial effects of nematode infection in autoimmune and inflammatory pathologies.

  11. Increase of precursor frequency and clonal size of murine IgE-secreting cells by IL-4

    NARCIS (Netherlands)

    Savelkoul, H.F.J.; Lebman, D.A.; Benner, R.; Coffman, R.L.

    1988-01-01

    IL-4 is able to preferentially enhance murine IgE levels in the supernatant of LPS-stimulated T cell-depleted splenic B cell cultures. Clonal and quantitative analysis of this response revealed that this is due partly to a 14-fold increased IgE precursor frequency and partly to a three-fold increase

  12. IL-4 increases type 2, but not type 1, cytokine production in CD8+ T cells from mild atopic asthmatics

    Directory of Open Access Journals (Sweden)

    Coyle Anthony J

    2005-07-01

    Full Text Available Abstract Background Virus infections are the major cause of asthma exacerbations. CD8+ T cells have an important role in antiviral immune responses and animal studies suggest a role for CD8+ T cells in the pathogenesis of virus-induced asthma exacerbations. We have previously shown that the presence of IL-4 during stimulation increases the frequency of IL-5-positive cells and CD30 surface staining in CD8+ T cells from healthy, normal subjects. In this study, we investigated whether excess IL-4 during repeated TCR/CD3 stimulation of CD8+ T cells from atopic asthmatic subjects alters the balance of type 1/type 2 cytokine production in favour of the latter. Methods Peripheral blood CD8+ T cells from mild atopic asthmatic subjects were stimulated in vitro with anti-CD3 and IL-2 ± excess IL-4 and the expression of activation and adhesion molecules and type 1 and type 2 cytokine production were assessed. Results Surface expression of very late antigen-4 [VLA-4] and LFA-1 was decreased and the production of the type 2 cytokines IL-5 and IL-13 was augmented by the presence of IL-4 during stimulation of CD8+ T cells from mild atopic asthmatics. Conclusion These data suggest that during a respiratory virus infection activated CD8+ T cells from asthmatic subjects may produce excess type 2 cytokines and may contribute to asthma exacerbation by augmenting allergic inflammation.

  13. 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

  14. Lol p I-induced IL-4 and IFN-gamma production by peripheral blood mononuclear cells of atopic and nonatopic subjects during and out of the pollen season.

    Science.gov (United States)

    Gagnon, R; Akoum, A; Hébert, J

    1993-04-01

    The reciprocal effects of IL-4 and IFN-gamma on IgE synthesis have been well established. It has also been shown that these two lymphokines are secreted by different subsets of CD4+ T cells (TH1 and TH2), and that TH2 helper T lymphocytes could be involved in the pathophysiology of allergic diseases. But little is known about the effects of an allergen on the profile of lymphokine synthesis by human peripheral blood mononuclear cells (PBMCs) of allergic and nonallergic subjects. We studied the production of IL-4 and IFN-gamma by PBMCs of atopic and nonatopic donors after in vitro stimulation by the group 1 allergen from Lolium perenne pollen (Lol p I), during and out of the grass pollen season. On natural exposure to pollen, Lol p I-induced IL-4 production was observed only with atopic donors (6 of 8), whereas the synthesis of IFN-gamma was observed for all nonatopic donors (7 of 7) and most allergic patients (5 of 7). At the time of the study, higher amounts of IFN-gamma were produced by PBMCs of nonatopic donors than by PBMCs of atopic patients. Out of the pollen season the production of IL-4 was not observed either by atopic (n = 11) or by nonatopic subjects (n = 5). On the other hand, IFN-gamma was produced by PBMCs of most subjects (atopic, 10 of 11; nonatopic, 5 of 5), but at the time of the study no difference was observed between the two groups. These results show that Lol p I induces different profiles of IL-4 and IFN-gamma production by PBMCs of atopic and nonatopic subjects. In atopic subjects this profile of lymphokine synthesis is influenced by the natural exposure to pollen, which is in keeping with the seasonal rise of IgE antibodies.

  15. The Interleukin-13 Receptor-α1 Chain Is Essential for Induction of the Alternative Macrophage Activation Pathway by IL-13 but Not IL-4.

    Science.gov (United States)

    Sheikh, Faruk; Dickensheets, Harold; Pedras-Vasconcelos, Joao; Ramalingam, Thirumalai; Helming, Laura; Gordon, Siamon; Donnelly, Raymond P

    2015-01-01

    Macrophages coexpress both the interleukin (IL)-2Rγ chain (γ(c)) and IL-13Rα1. These receptor chains can heterodimerize with IL-4Rα to form type I or type II IL-4 receptor complexes, respectively. We used macrophages derived from Il2rg and Il13ra1 knockout (KO) mice to evaluate the requirements for these receptor chains for induction of the alternative macrophage activation (AMA) pathway by IL-4 and IL-13. Absence of γ(c) significantly decreased activation of STAT6 by IL-4 but not IL-13. However, although activation of STAT6 by IL-4 was markedly reduced in γ(c) KO macrophages, it was not abolished, indicating that IL-4 can still signal through type II IL-4 receptors via the IL-13Rα1 chain. IL-13 failed to activate STAT6 in macrophages derived from Il13ra1 KO mice; however, these cells remained fully responsive to IL-4. The inability of IL-13 but not IL-4 to signal in Il13ra1(-/-) macrophages correlated with the inability of IL-13 but not IL-4 to induce expression of genes such as Arg1, Retnla and Ccl11 that are characteristically expressed by alternatively activated macrophages. In addition, IL-13 but not IL-4 failed to induce membrane fusion and giant cell formation by Il13ra1 KO macrophages. These findings demonstrate that the IL-13Rα1 chain is essential for induction of the AMA pathway by IL-13 but not IL-4.

  16. Common Membrane Trafficking Defects of Disease Associated Dynamin 2 Mutations

    OpenAIRE

    Liu, Ya-Wen; Lukiyanchuk, Vasyl; Schmid, Sandra L.

    2011-01-01

    Dynamin (Dyn) is a multidomain and multifunctional GTPase best known for its essential role in clathrin-mediated endocytosis (CME). Dyn2 mutations have been linked to two human diseases, Centronuclear Myopathy (CNM) and Charcot-Marie-Tooth (CMT) disease. Paradoxically, although Dyn2 is ubiquitously expressed and essential for embryonic development, the disease-associated Dyn2 mutants are autosomal dominant, but result in slowly progressing and tissue-specific diseases. Thus, although the cell...

  17. Complement genetics, deficiencies, and disease associations.

    Science.gov (United States)

    Mayilyan, Karine R

    2012-07-01

    The complement system is a key component of innate immunity. More than 45 genes encoding the proteins of complement components or their isotypes and subunits, receptors, and regulators have been discovered. These genes are distributed throughout different chromosomes, with 19 genes comprising three significant complement gene clusters in the human genome. Genetic deficiency of any early component of the classical pathway (C1q, C1r/s, C2, C4, and C3) is associated with autoimmune diseases due to the failure of clearance of immune complexes (IC) and apoptotic materials, and the impairment of normal humoral response. Deficiencies of mannan-binding lectin (MBL) and the early components of the alternative (factor D, properdin) and terminal pathways (from C3 onward components: C5, C6, C7, C8, C9) increase susceptibility to infections and their recurrence. While the association of MBL deficiency with a number of autoimmune and infectious disorders has been well established, the effects of the deficiency of other lectin pathway components (ficolins, MASPs) have been less extensively investigated due to our incomplete knowledge of the genetic background of such deficiencies and the functional activity of those components. For complement regulators and receptors, the consequences of their genetic deficiency vary depending on their specific involvement in the regulatory or signalling steps within the complement cascade and beyond. This article reviews current knowledge and concepts about the genetic load of complement component deficiencies and their association with diseases. An integrative presentation of genetic data with the latest updates provides a background to further investigations of the disease association investigations of the complement system from the perspective of systems biology and systems genetics.

  18. Costimulation of resting B lymphocytes alters the IL-4-activated IRS2 signaling pathway in a STAT6 independent manner: implications for cell survival and proliferation

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    IL-4 is an important B cell survival and growth factor.IL-4 induced the tyrosine phosphorylation of IRS2 in resting B lymphocytes and in LPS- or CD40L-activated blasts.Phosphorylated IRS2 coprecipitated with the p85 subunit of PI 3' kinase in both resting and activated cells.By contrast,association of phosphorylated IRS2 with GRB2 was not detected in resting B cells after IL-4 treatment although both proteins were expressed.However,IL-4 induced association of IRS2 with GRB2 in B cell blasts.The pattern of IL-4-induced recruitment of p85 and GRB2 to IRS2 observed in B cells derived from STAT6 null mice was identical to that observed for normal mice.While IL-4 alone does not induce activation of MEK,a MEK1 inhibitor suppressed the IL-4-induced proliferative response of LPS-activated B cell blasts.These results demonstrate that costimulation of splenic B cells alters IL-4-induced signal transduction independent of STAT6 leading to proliferation.Furthermore,proliferation induced by IL-4 in LPS-activated blasts is dependent upon the MAP kinase pathway.

  19. Regulation of the Il4 Gene Is Independently Controlled by Proximal and Distal 3′ Enhancers in Mast Cells and Basophils▿

    OpenAIRE

    Yagi, Ryouji; Tanaka, Shinya; Motomura, Yasutaka; Kubo, Masato

    2007-01-01

    Mast cells and basophils are known to be a critical interleukin 4 (IL-4) source for establishing Th2 protective responses to parasitic infections. Chromatin structure and histone modification patterns in the Il13/Il4 locus of mast cells were similar to those of IL-4-producing type 2 helper T cells. However, using a transgenic approach, we found that Il4 gene expression was distinctly regulated by individual cis regulatory elements in cell types of different lineages. The distal 3′ element con...

  20. Angiogenesis related genes NOS3, CD14, MMP3 and IL4R are associated to VEGF gene expression and circulating levels in healthy adults

    OpenAIRE

    Saleh, Abdelsalam; Stathopoulou, Maria G.; Dadé, Sébastien; Ndiaye, Ndeye Coumba; Azimi-Nezhad, Mohsen; Murray, Helena; Masson, Christine; Lamont, John; Fitzgerald, Peter; Visvikis-Siest, Sophie

    2015-01-01

    Background Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis. The aim was to assess the genetic connections between the angiogenesis-related NOS3, CD14, MMP3, IL4R, IL4 genes and VEGF expression and plasma levels. Methods The associations between VEGF plasma levels with the polymorphisms of NOS3, CD14, MMP3, IL4R, and IL4 were assessed in 403 healthy unrelated adults. The epistatic and environmental interactions were explored, including four VEGF-related polymorphisms...

  1. The influence of drinking-water pollution with heavy metal on the expression of IL-4 and IFN-γ in mice by real-time polymerase chain reaction

    OpenAIRE

    Radbin, Rayhaneh; Vahedi, Fatemeh; Chamani, Jamshidkhan

    2013-01-01

    In recent years, water pollution has been converted to a challenging discussion in health area of human being. Heavy elements are one of the most important water pollutants and their negative adverse effects on body systems have been confirmed. In this study, investigation of effects of two heavy elements including lead (Pb) and copper (Cu) on expression of interlukin-4 (IL-4) and interferon-gamma (IFN-γ) as humoral and cellular immunity biomarkers, respectively, was aimed and PCR, real-time ...

  2. Cytometric evaluation of intracellular IFN-γ and IL-4 levels in thyroid follicular cells from patients with autoimmune thyroid diseases

    Directory of Open Access Journals (Sweden)

    Bossowski Artur

    2011-09-01

    Full Text Available Abstract Background In recent few years is underlined that altered balance of pro- and anti-inflammatory cytokines play an important role in the pathogenesis of AITD. The aim of this study was to estimate intracellular INF-γ and IL-4 levels in thyroid-infiltrating lymphocytes and thyrocytes isolated from thyroid tissues in 54 adolescent patients aged 8-21 years, with Graves' disease (GD; n = 18, Hashimoto's thyroiditis (HT; n = 18 and non-toxic multinodular goiter (NTMG; n = 18. Methods Fresh thyroid tissues were taken on culture medium RPMI -1640, it was mechanically prepared. In next step were added cell activators -12- myristate 13- the acetate (PMA and Ionomycin as well as the inhibitor of transportation of proteins - Breferdin A. They were cultured 24 hours in 50 ml flasks at 37°C in a 5-95% CO2-air water-saturated atmosphere. After that, thyrocytes were identified by mouse mAb directed against human TPO epitope 64 conjugated with rabbit anti-mouse antibodies IgG (Fab'2 labeled by FITC. After incubation at room temperature to each of samples added reagent A fixative the cellular membrane. In next step into the cell suspensions were added reagent B to permeabilization of cellular membrane and specific anti-IL-4-PE or anti-IFN-γ-PE mAbs. Identification of intracellular cytokines in T lymphocytes was performed in the same procedure with application of anti-CD4-PerCP and anti-CD8-PerCP mAbs specific for T lymphocytes. The cells were analyzed in a flow cytometry (Coulter EPICS XL. Results In examined group of patients with GD we observed statistically significant higher mean percentage of cells with phenotype CD4+IL-4 (p Conclusions We conclude that human thyrocytes in autoimmune thyroid disorders could be a source of cytokine production and that their activation influences local interaction with T lymphocytes inflowing to the thyroid gland.

  3. Disease-associated mutations that alter the RNA structural ensemble.

    Directory of Open Access Journals (Sweden)

    Matthew Halvorsen

    2010-08-01

    Full Text Available Genome-wide association studies (GWAS often identify disease-associated mutations in intergenic and non-coding regions of the genome. Given the high percentage of the human genome that is transcribed, we postulate that for some observed associations the disease phenotype is caused by a structural rearrangement in a regulatory region of the RNA transcript. To identify such mutations, we have performed a genome-wide analysis of all known disease-associated Single Nucleotide Polymorphisms (SNPs from the Human Gene Mutation Database (HGMD that map to the untranslated regions (UTRs of a gene. Rather than using minimum free energy approaches (e.g. mFold, we use a partition function calculation that takes into consideration the ensemble of possible RNA conformations for a given sequence. We identified in the human genome disease-associated SNPs that significantly alter the global conformation of the UTR to which they map. For six disease-states (Hyperferritinemia Cataract Syndrome, beta-Thalassemia, Cartilage-Hair Hypoplasia, Retinoblastoma, Chronic Obstructive Pulmonary Disease (COPD, and Hypertension, we identified multiple SNPs in UTRs that alter the mRNA structural ensemble of the associated genes. Using a Boltzmann sampling procedure for sub-optimal RNA structures, we are able to characterize and visualize the nature of the conformational changes induced by the disease-associated mutations in the structural ensemble. We observe in several cases (specifically the 5' UTRs of FTL and RB1 SNP-induced conformational changes analogous to those observed in bacterial regulatory Riboswitches when specific ligands bind. We propose that the UTR and SNP combinations we identify constitute a "RiboSNitch," that is a regulatory RNA in which a specific SNP has a structural consequence that results in a disease phenotype. Our SNPfold algorithm can help identify RiboSNitches by leveraging GWAS data and an analysis of the mRNA structural ensemble.

  4. Cloning and sequence analysis of IL-2, IL-4 and IFN-γ from Indian Dromedary camels (Camelus dromedarius).

    Science.gov (United States)

    Nagarajan, G; Swami, Shelesh Kumar; Ghorui, S K; Pathak, K M L; Singh, R K; Patil, N V

    2012-06-01

    The cDNAs of three cytokines, viz., IL-2, IL-4 and IFN-γ from Dromedary camels were amplified by PCR using Bactrian camel sequences and subsequently cloned for sequence analysis. Relationship based on amino acid sequences revealed that Dromedary camel IL-2 shared 99.5% and 99.3% identity at the nucleotide and amino acid levels with Bactrian camel IL-2. In the case of IL-4, the identity of Dromedary camel was 99.7% and 99.2% at the nucleotide and amino acid levels, respectively with that of Bactrian camel. The Dromedary camel IFN-γ shared 100% identity both at nucleotide and amino acid levels with Bactrian camel IFN-γ. Phylogenetic analysis based on amino acid sequences indicated the close relationship in these cytokine genes between the Dromedary camel and other camelids.

  5. IL-4-producing murine T helper cell line provides help for in vitro production of IgE

    DEFF Research Database (Denmark)

    Poulsen, L K; Katamura, K; Ishizaka, K

    1991-01-01

    with nonadherent splenocytes from normal MHC-matched mice. Help provided by the antigen-stimulated T cell line induced significant IgE production (20 ng/ml), along with IgG1 (5 micrograms/ml) and IgM (250 micrograms/ml). Immunoglobulin synthesis in cultures was detectable at day 3-4 and culminated at day 7-8. IL-4...... synthesis of IgE. The presence of interferon-gamma in the cultures, inhibited synthesis of IgE, IgM and IgG1, but this inhibition was not due to interference with the IL-4 production, which increased in the presence of high doses of interferon-gamma....

  6. Cognate interactions: extrafollicular IL-4 drives germinal-center reactions, a new role for an old cytokine.

    Science.gov (United States)

    Toellner, Kai-Michael

    2014-07-01

    Over the past 25 years it has become clear that B and T lymphocytes go through a range of interactions and migratory events when B cells differentiate to become high-affinity, antibody-secreting cells. This B-cell differentiation is associated with multiple sequential cognate interactions. In this issue of the European Journal of Immunology, Turqueti-Neves et al. [Eur. J. Immunol. 2014. 44: 2130-2138] show that IL-4, a cytokine well known as a regulator of Ig class switch recombination, has another as-yet-unappreciated role. The authors show that IL-4 produced by T-helper cells outside germinal centers has a major effect on the early stages of germinal-center B-cell differentiation. This Commentary will summarize their findings and relate them to what we know on the sequence of cognate interactions and migratory events B cells undergo during T-dependent immune responses.

  7. EFFECTS OF IL-4 UPON THE ACTIVITY OF STAT6 TRANSCRIPTION FACTOR IN PERIPHERAL BLOOD LYMPHOCYTES IN BRONCHIAL ASTHMA

    Directory of Open Access Journals (Sweden)

    V. N. Mineev

    2009-01-01

    Full Text Available Abstract. The aim of the study is to specify the levels of STAT6, and phospho-STAT6 under the influence of IL-4 in patients with bronchial asthma (BA. The samples from ten healthy controls and thirty-three BA patients with allergic and non-allergic clinical forms of different severity were under investigation. Peripheral blood lymphocytes were treated with 10 ng/ml of IL-4 (Sigma Aldrich, USA for 1 h. Then the proteins (STAT6 and phospho-STAT6 expressed in peripheral lymphocytes were analyzed by Western blot of cell lysates. Preparation of the cell lysates and Western blotting were carried out using standard procedures. Antibodies against phospho-STAT6 and STAT6 (10 ng/ml were used (Cell Signaling, USA. Levels of thespecific proteins were standardized according to β-actin (Cell Signaling, USA. Treatment with IL-4 caused an increase of phospho-STAT6 levels in lymphocytes of all BA patients, as compared with control group. In allergic BA, the phospho-STAT6 levels were significantly higher than in non-allergic clinical forms. Expression of STAT6 in lymphocytes of patients with severe BA was significantly higher, as compared to BA of moderate severity. An IL-4-induced activation of the STAT6 transcription factor was revealed in an in vitro system, being mostly expressed in allergic BA. The level of STAT6 may serve as a BA severity index. This study was supported by a «Scholarship of the Year» grant from the St. Petersburg State Medical I. Pavlov University (2007.

  8. Extracellular vesicles released by CD40/IL-4-stimulated CLL cells confer altered functional properties to CD4+ T cells.

    Science.gov (United States)

    Smallwood, Dawn T; Apollonio, Benedetta; Willimott, Shaun; Lezina, Larissa; Alharthi, Afaf; Ambrose, Ashley R; De Rossi, Giulia; Ramsay, Alan G; Wagner, Simon D

    2016-07-28

    The complex interplay between cancer cells, stromal cells, and immune cells in the tumor microenvironment (TME) regulates tumorigenesis and provides emerging targets for immunotherapies. Crosstalk between CD4(+) T cells and proliferating chronic lymphocytic leukemia (CLL) tumor B cells occurs within lymphoid tissue pseudofollicles, and investigating these interactions is essential to understand both disease pathogenesis and the effects of immunotherapy. Tumor-derived extracellular vesicle (EV) shedding is emerging as an important mode of intercellular communication in the TME. In order to characterize tumor EVs released in response to T-cell-derived TME signals, we performed microRNA (miRNA [miR]) profiling of EVs released from CLL cells stimulated with CD40 and interleukin-4 (IL-4). Our results reveal an enrichment of specific cellular miRNAs including miR-363 within EVs derived from CD40/IL-4-stimulated CLL cells compared with parental cell miRNA content and control EVs from unstimulated CLL cells. We demonstrate that autologous patient CD4(+) T cells internalize CLL-EVs containing miR-363 that targets the immunomodulatory molecule CD69. We further reveal that autologous CD4(+) T cells that are exposed to EVs from CD40/IL-4-stimulated CLL cells exhibit enhanced migration, immunological synapse signaling, and interactions with tumor cells. Knockdown of miR-363 in CLL cells prior to CD40/IL-4 stimulation prevented the ability of CLL-EVs to induce increased synapse signaling and confer altered functional properties to CD4(+) T cells. Taken together, these data reveal a novel role for CLL-EVs in modifying T-cell function that highlights unanticipated complexity of intercellular communication that may have implications for bidirectional CD4(+) T-cell:tumor interactions within the TME. © 2016 by The American Society of Hematology.

  9. Effect of Point Application in Dog Days on Serum IgE, IL-4, IFN-γ in Patients with Allergic Rhinitis%三伏天穴位敷贴疗法对变应性鼻炎患者血清IgE、IL-4、IFN-γ的影响

    Institute of Scientific and Technical Information of China (English)

    林佳静; 何晓华; 胡雨华; 王彦成; 孙伯坚; 韩梅

    2011-01-01

    Objective To establish a prokaryotio expression vector for FcγRIIb extracellular gene, to induce its expression and to purify the protein. Methods The human FcγRIIb extracellular gene was amplified by PCR and inserted into pET32a( + ).The recombinant vector pET -sFcγRIIb was analyzed by PCR,restriction enzyme digestion and DNA sequencing. The recombinant vector pET - sFcγRIIb was transformed into BL21. Through observing protein expression induced by IPTG at different temperature and time, the best induced conditionswere confirmed. The protein was detected by SDS - PAGE and then purified. Results The recombi-nant vector pET - sFcyRIIb was constructed and the husFcγRHb protein was successfully expressed after in-duced 10 hours by IPTG in SOX, and purified. Conclusion We have got the fusion protein of hus FcγRIIb by establishing pET - s FcyRIIb and laid a basis for further study of husFcγRIIb protein.%目的 观察三伏天穴位敷贴疗法对变应性鼻炎患者血清IgE及IL-4、IFN-γ的影响,为经腧穴处皮肤给药刺激经络系统达到调节免疫,治疗变应性疾病提供依据.方法 在农历三伏天对变应性鼻炎患者进行穴位敷贴治疗,采用放射免疫法检测变应性鼻炎患者治疗前后及健康体检者血清IgE、IL-4和IFN-γ.结果 治疗前变应性鼻炎患者血清总IgE及IL-4水平明显高于健康体检者(P<0.01),血清IFN-γ与健康体检者相比差异无统计学意义(P>0.05).经1个疗程穴位敷贴治疗后,患者血清总IgE较治疗前明显降低(P<0.05),但IL-4和IFN-γ无明显变化(P>0.05).结论 穴位敷贴疗法治疗变应性鼻炎可降低血清IgE水平.

  10. Comparative evaluation of IFNγ, IL4 and IL17 cytokines in healthy gingiva and moderate to advanced chronic periodontitis

    Directory of Open Access Journals (Sweden)

    Parichehr Behfarnia

    2010-01-01

    Full Text Available Background: Considering the role of T cells in the pathogenesis of periodontitis, the purpose of this study was to compare the amount of IFNγ, IL4 and IL17 in advanced periodontal lesions with healthy gum areas to determine each TH1, TH2 and TH17 cells activity in comparison with each other and finally, to compare the value and the role of humoral, cell mediate and autoimmune responses. Methods : In this descriptive analytical study, those with moderate to advanced periodontitis, having pocket with 4 to 7 mm in depth, were randomly selected. After preparing the healthy and affected sample tissues, the amount of the specific antibody in I IFNγ, IL4 and IL17 cytokines were measured using ELISA method and were compared between the two groups. The findings were analyzed using the software and descriptive statistical methods and Pearson correlation statistical analysis (α = 0.05. Results: This study was performed on 37 patients with moderate to severe periodontitis and 22 healthy individuals without any periodontal disease. IL4 and IFNγ levels in the patients with chronic periodontitis compared to those of healthy gingival samples showed a significant reduction (P > 0.05 whereas the amount of IL17 in tissue samples of chronic periodontitis compared to healthy gums had a significant increase (P < 0.05. Conclusion: It appears that in the periodontitis pathogenesis, as well as TH1 and TH2 responses, IL17 causes the host immunological response to the periodontal pathogenesis.

  11. 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......(+) (approximately 40% apoptotic cells) B cell cultures as well as B cell lines, but has no effect on chemotaxis or cell adhesion. Freshly isolated B cells express low levels of CD95 and CD95 ligand (CD95L) (19 and 21%, respectively). Expression is up-regulated on culture in the presence of a combination of IL-2, IL......-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...

  12. Disease-associated mutations prevent GPR56-collagen III interaction.

    Directory of Open Access Journals (Sweden)

    Rong Luo

    Full Text Available GPR56 is a member of the adhesion G protein-coupled receptor (GPCR family. Mutations in GPR56 cause a devastating human brain malformation called bilateral frontoparietal polymicrogyria (BFPP. Using the N-terminal fragment of GPR56 (GPR56(N as a probe, we have recently demonstrated that collagen III is the ligand of GPR56 in the developing brain. In this report, we discover a new functional domain in GPR56(N, the ligand binding domain. This domain contains four disease-associated mutations and two N-glycosylation sites. Our study reveals that although glycosylation is not required for ligand binding, each of the four disease-associated mutations completely abolish the ligand binding ability of GPR56. Our data indicates that these four single missense mutations cause BFPP mostly by abolishing the ability of GPR56 to bind to its ligand, collagen III, in addition to affecting GPR56 protein surface expression as previously shown.

  13. T cell subsets and cytokines in allergic and non-allergic children. I. Analysis of IL-4, IFN-? and IL-13 mRNA expression and protein production

    NARCIS (Netherlands)

    Koning, H.; Neijens, H.J.; Baert, M.R.M.; Oranje, A.P.; Savelkoul, H.F.J.

    1997-01-01

    Interleukin 4 (IL-4) and IL-13 are key cytokines inducing switching to immunoglobulin E (IgE), whereas interferon (IFN-) acts inhibitory on this process. We analysed whether differences existed in IL-4, IFN- and IL-13 mRNA expression and protein production between T cells of children with allergic a

  14. Conditional IL-4/IL-13-deficient mice reveal a critical role of innate immune cells for protective immunity against gastrointestinal helminths.

    Science.gov (United States)

    Oeser, K; Schwartz, C; Voehringer, D

    2015-05-01

    Approximately one-third of the world population is infected with gastrointestinal helminths. Studies in mouse models have demonstrated that the cytokines interleukin (IL)-4 and IL-13 are essential for worm expulsion, but the critical cellular source of these cytokines is poorly defined. Here, we compared the immune response to Nippostrongylus brasiliensis in wild-type, T cell-specific IL-4/IL-13-deficient and general IL-4/IL-13-deficient mice. We show that T cell-derived IL-4/IL-13 promoted T helper 2 (Th2) polarization in a paracrine manner, differentiation of alternatively activated macrophages, and tissue recruitment of innate effector cells. However, innate IL-4/IL-13 played the critical role for induction of goblet cell hyperplasia and secretion of effector molecules like Mucin5ac and RELMβ in the small intestine. Surprisingly, T cell-specific IL-4/IL-13-deficient and wild-type mice cleared the parasite with comparable efficiency, whereas IL-4/IL-13-deficient mice showed impaired expulsion. These findings demonstrate that IL-4/IL-13 produced by cells of the innate immune system is required and sufficient to initiate effective type 2 immune responses resulting in protective immunity against N. brasiliensis.

  15. T cell subsets and cytokines in allergic and non-allergic children. I. Analysis of IL-4, IFN-? and IL-13 mRNA expression and protein production

    NARCIS (Netherlands)

    Koning, H.; Neijens, H.J.; Baert, M.R.M.; Oranje, A.P.; Savelkoul, H.F.J.

    1997-01-01

    Interleukin 4 (IL-4) and IL-13 are key cytokines inducing switching to immunoglobulin E (IgE), whereas interferon (IFN-) acts inhibitory on this process. We analysed whether differences existed in IL-4, IFN- and IL-13 mRNA expression and protein production between T cells of children with allergic

  16. The Effect of Vitamin A on Secretion of IFN-γ and IL-4 in A549 Cells Induced by Mycoplasma Pneumoniae

    Institute of Scientific and Technical Information of China (English)

    Xiaolan WU; Xianzhou LIU; Jilu TANG

    2008-01-01

    In order to investigate the effect of vitamin A (VA) on the secretion of IFN-γ and IL-4 in Mycoplasma Pneumoniae (MP)-induced A549 cells, A549 cells were co-cultured with MP for different time lengths and then the levels of IFN-γ and IL-4 in the cell culture supematants were detected before and after treatment with different concentrations of VA by using the enzyme-linked immunosorbent assay (ELISA). The results showed that the level of IFN-γ and IL-4 in the supernatants of MP-induced A549 cells was much higher than that in non-induced cells (P<0.01). After application of VA, IL-4 level was not increased until the concentration of VA was up to 0.5 × 10-5 mol/L (P<0.01).However, with concentration of VA increased up to 1 × 10-4 mol/L, IL-4 was significantly suppressed (P<0.01). It was concluded that MP could induce the secretion of IFN-y and IL-4 in A549 cells. VA could inhibit the secretion of IFN-γ, and increase the IL-4 level in MP-induced A549 cells. However,high concentration of VA had an inhibitory effect on the secretion of IL-4 as well as on the IFN-γ.These data provided a theoretical basis for the application of VA in MP pneumonia in the clinical practice.

  17. IL-4Rα-dependent alternative activation of macrophages is not decisive for Mycobacterium tuberculosis pathology and bacterial burden in mice.

    Directory of Open Access Journals (Sweden)

    Reto Guler

    Full Text Available Classical activation of macrophages (caMph or M1 is crucial for host protection against Mycobacterium tuberculosis (Mtb infection. Evidence suggests that IL-4/IL-13 alternatively activated macrophages (aaMph or M2 are exploited by Mtb to divert microbicidal functions of caMph. To define the functions of M2 macrophages during tuberculosis (TB, we infected mice deficient for IL-4 receptor α on macrophages (LysMcreIL-4Rα-/lox with Mtb. We show that absence of IL-4Rα on macrophages does not play a major role during infection with Mtb H37Rv, or the clinical Beijing strain HN878. This was demonstrated by similar mortality, bacterial burden, histopathology and T cell proliferation between infected wild-type (WT and LysMcreIL-4Rα-/lox mice. Interestingly, we observed no differences in the lung expression of inducible nitric oxide synthase (iNOS and Arginase 1 (Arg1, well-established markers for M1/M2 macrophages among the Mtb-infected groups. Kinetic expression studies of IL-4/IL-13 activated bone marrow-derived macrophages (BMDM infected with HN878, followed by gene set enrichment analysis, revealed that the MyD88 and IL-6, IL-10, G-CSF pathways are significantly enriched, but not the IL-4Rα driven pathway. Together, these results suggest that IL-4Rα-macrophages do not play a central role in TB disease progression.

  18. IL-4/IL-13-dependent and independent expression of miR-124 and its contribution to M2 phenotype of monocytic cells in normal conditions and during allergic inflammation.

    Directory of Open Access Journals (Sweden)

    Tatyana Veremeyko

    Full Text Available Monocytic cells exhibit a high level of heterogeneity and have two distinct modes of their activation: 1 classical M1 path associated with inflammation and tissue damage, and 2 alternative M2 path. Although it has been demonstrated that M2 macrophages play an important role in the regulation of the allergic immune responses, tissue maintenance and repair, little is known about the mechanisms that determine the M2 phenotype. We have previously shown that miR-124 is expressed in microglia that exhibit the M2 phenotype and overexpression of miR-124 in macrophages resulted in downregulation of a number of M1 markers (MHC class II, CD86 and up-regulation of several M2 markers (Fizz1, Arg1. We further investigated whether the polarization of macrophages towards the M2 phenotype induced miR-124 expression. We found that exposure of cells to IL-4 and IL-13 resulted in the upregulation of miR-124 in macrophages. We also demonstrated that IL-4 induced expression of three miR-124 precursor transcripts with predominant expression of pri-miR-124.3, suggesting regulation of miR-124 expression by IL-4 on a transcriptional level. Expression of miR-124 in microglia did not depend on IL-4 and/or IL-13, whereas expression of miR-124 in lung resident macrophages was IL-4 and IL-13-dependent and was upregulated by systemic administration of IL-4 or during allergic inflammation. Upregulation of several M2 markers (CD206, Ym1 and downregulation of the M1 markers (CD86, iNOS, TNF in M2-polarized macrophages was abrogated by a miR-124 inhibitor, suggesting that this microRNA contributed to the M2 phenotype development and maintenance. Finally we showed that human CD14(+CD16(+ intermediate monocytes, which are found in increased numbers in patients with allergies and bronchial asthma, expressed high levels of miR-124 and exhibited other properties of M2-like cells. Thus, our study suggests that miR-124 serves as a regulator of the M2 polarization in various subsets of

  19. Filarial infection modulates the immune response to Mycobacterium tuberculosis through expansion of CD4+ IL-4 memory T cells.

    Science.gov (United States)

    Chatterjee, Soumya; Clark, Carolyn E; Lugli, Enrico; Roederer, Mario; Nutman, Thomas B

    2015-03-15

    Exaggerated CD4(+) T helper 2-specific cytokine producing memory T cell responses developing concomitantly with a T helper 1 response might have a detrimental role in immunity to infection caused by Mycobacterium tuberculosis. To assess the dynamics of Ag-specific memory T cell compartments in the context of filarial infection, we used multiparameter flow cytometry on PBMCs from 25 microfilaremic filarial-infected (Inf) and 14 filarial-uninfected (Uninf) subjects following stimulation with filarial Ag (BmA) or with the M. tuberculosis-specific Ag culture filtrate protein-10 (CFP-10). Our data demonstrated that the Inf group had a marked increase in BmA-specific CD4(+)IL-4(+) cells (median net frequency compared with baseline [Fo] = 0.09% versus 0.01%; p = 0.038) but also to CFP-10 (Fo = 0.16% versus 0.007%; p = 0.04) and staphylococcal enterotoxin B (Fo = 0.49% versus 0.26%; p = 0.04). The Inf subjects showed a BmA-specific expansion of CD4(+)CD45RO(+)IL-4(+) producing central memory (TCM, CD45RO(+)CCR7(+)CD27(+); Fo = 1.1% versus 0.5%; p = 0.04) as well as effector memory (TEM, CD45RO(+)CCR7(-)CD27(-); Fo = 1.5% versus 0.2%; p = 0.03) with a similar but nonsignificant response to CFP-10. In addition, there was expansion of CD4(+)IL-4(+)CD45RA(+)CCR7(+)CD27(+) (naive-like) in Inf individuals compared with Uninf subjects. Among Inf subjects with definitive latent tuberculosis, there were no differences in frequencies of IL-4-producing cells within any of the memory compartments compared with the Uninf group. Our data suggest that filarial infection induces Ag-specific, exaggerated IL-4 responses in distinct T cell memory compartments to M. tuberculosis-specific Ags, which are attenuated in subjects who are able to mount a delayed type hypersensitivity reaction to M. tuberculosis.

  20. Effect of IL-4 on altered expression of complement activation regulators in rat pancreatic cells during severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Cheng Zhang; Chun-Lin Ge; Ren-Xuan Guo; San-Guang He

    2005-01-01

    AIM: To investigate the effect of IL-4 on the altered expression of complement activation regulators in pancreas and pancreatic necrosis during experimental severe acute pancreatitis (SAP).METHODS: SAP model of rats was established by retrograde injection of 5% sodium taurocholate (1 mL/kg)into the pancreatic duct. We immunohistochemically assayed the expression of three complement activation regulators: decay accelerating factor (DAF; CD55), 20ku homologous restriction factor (HRF20; CD59) and membrane cofactor protein (MCP; CD46), in the pancreatic acinar cells of rats at 0, 3, 6, 12, and 24 h after the induction of SAP model. Meanwhile the levels of amylase and lipase were determined, and morphological examination was performed. Then, 61 rats were randomly divided into three groups. Group A (n = 21) received notreatment after the SAP model was established; group B (n = 20) was given IL-4 (8 μg/animal) intraperitoneally 0.5 h before the SAP model was established; group C (n = 20) was given IL-4 (8 μg/animal) intraperitoneally 0.5 h after the SAP model was established. Plasma amylase and lipase, extent of pancreatic necrosis and expression of complement activation regulators were investigated 6 h after the induction of SAP model.RESULTS: Three complement activation regulators were all expressed in pancreatic acinar cells. MCP was not found on the basolateral surface as reported. Contrary to the gradually increasing plasma level of amylase and lipase, expression of complement activation regulators decreased after SAP model was set up. At the same time, the severity of pancreatic necrosis was enhanced.A strong negative correlation was found between the expression of MCP, DAF, CD59 in pancreatic acinar cells and the severity of pancreatic necrosis (r = -0.748, -0.827,-0.723; P<0.01). In the second series of experiments,no matter when the treatment of IL-4 was given (before or after the induction of SAP model), the serum level of amylase or lipase Was decreased

  1. Short-term stimulation with interleukin (IL-4 enhances purified protein derivative-induced production of an eosinophil chemotactic lymphokine, but suppresses IL-5 production

    Directory of Open Access Journals (Sweden)

    Takehiko Nishiyama

    1998-01-01

    Full Text Available The effect of interleukin (IL-4 on eosinophil chemotactic lymphokine (ECL production from peripheral blood mononuclear cells (PBMC stimulated with purified protein derivative (PPD was examined. The PBMC stimulated with PPD in the absence of IL-4 failed to produce evident ECL. However, PPD-induced eosinophil chemotactic activity (ECA production was markedly enhanced in a dose-dependent manner by pretreatment of PBMC with IL-4. The most potent enhancement was induced by IL-4 at a concentration of 30 U in tuberculin-sensitive PBMC. Short-term pretreatment (30 min to 3 h was sufficient for the enhancement, whereas longer-term treatment was less effective. Eosinophil chemotactic lymphokine was found to be a CD4+ T cell-derived factor with an isoelectric point of approximately pH 7.0 and without heparin affinity, unlike chemokines such as RANTES and eotaxin. The effect of IL-4 on the production of other cytokines, such as interferon (IFN-γ, IL-5, RANTES (regulated on activation, normal T expressed and secreted, and granulocyte-macrophage colony stimulating factor (GM-CSF was also examined. Peripheral blood mononuclear cells produced all these cytokines when they were treated with PPD, even in the absence of IL-4. When PBMC were pretreated with IL-4, interestingly not only IFNy but also IL-5 production was suppressed by pretreatment with IL-4, although ECL production was enhanced by the pretreatment. In the case of RANTES and GM-CSF, significant amounts of these cytokines were produced, even without antigenic stimulation, and IL-4 pretreatment did not result in an enhancement of their production. It is thus suggested that IL-4, existing in allergic lesions, plays a crucial role in eosinophil accumulation mediated by the T cell-derived ECL.

  2. Effects of IL4 on Distribution of Fat Granule in Fasciola hepatica Elicited Macrophages%IL4对肝片吸虫感染诱导巨噬细胞中脂肪滴分布的影响

    Institute of Scientific and Technical Information of China (English)

    谌剑波; 郭智莉; 周容琼; 周作勇; 张文韬; 周雪梅; 罗洪林

    2013-01-01

    试验以肝片吸虫囊蚴经口分别感染雌性BALB/c野生型及其IL4单抗处置小鼠,运用特异性PCR鉴定成功感染小鼠后获取巨噬细胞,设立人工巯基醋酸盐诱导巨噬细胞对照组进行体外培养.用荧光定量PCR检测巨噬细胞的标记蛋白Relmα和Yml以确定其激活状态.将所获取的巨噬细胞的细胞质用特异性抗体染色,并用共聚焦显微镜拍摄不同时间点从不同小鼠体内获取的巨噬细胞染色后的图片.结果发现,Relmα和Yml基因在IL4单抗处置小鼠和巯基醋酸盐诱导小鼠的巨噬细胞中均表达,但在IL4单抗处置小鼠的表达量显著下降.脂肪滴分布在肝片吸虫诱导的选择性激活巨噬细胞的细胞质中,被染色成绿色且呈圆形.同时发现脂肪滴的分布形式多样,大小不一,既有单个分布也能成蔟分布.

  3. Dermatitis Granules on Serum IFN-γ IL-4%皮炎康颗粒对小鼠血清IFN-γIL-4的影响研究

    Institute of Scientific and Technical Information of China (English)

    刘彬

    2012-01-01

    Objective zTn investigate the heat and dampness, cooling Wood Shufeng, nourishing Qi role dermatitis granule anti-inflammatory, inhibiting the pharmacological action of the immune response. Methods : 2,4 - dinitrochlorohenzene ( DNCB ) to establish mice with chronic allergic contact dermatitis ( ACD ) model, set dermatitis granules ( 4 times the equivalent amount), ( 2 limes the equivalent volume ), low ( equivalent volume ) of the three-dose group and the loratadine given piece of high-dose ( 4 times ) group. Using enzyme-linked immunosorbent assay ( ELISA ) was the content of the of dermatitis granules of chronic ACD serum, inlerferon- γ ( IFN-gamma ), interleukin -4 ( IL-4 ) . Results : Dermatitis granules can be significantly improved to reduce chronic ACD model of serum IFN-γ levels and increased IL-4 level. Conclusion : It can be seen dermatitis granules have good suppression of the immune stress response.%目的:探讨具有清热利湿、凉血疏风、益气养血作用的皮炎康颗粒是否有抗炎、抑制免疫反应的药理学作用.方法:采用2,4-二硝基氯苯(DNCB)建立小鼠慢性变应性接触性皮炎(ACD)模型,设定皮炎康颗粒高(4倍等效量)、中(2倍等效量)、低(等效量)3个剂量组和氯雷他定片高剂量(4倍量)组.运用酶联免疫(ELISA)法检测皮炎康颗粒对慢性ACD小鼠血清中干扰素-γ(IFN-γ)、白细胞介素-4(IL-4)的含量的影响.结果:皮炎康颗粒可明显改善降低慢性ACD模型小鼠血清IFN-γ水平,并升高IL-4含量.结论:可以看出皮炎康颗粒具有良好的抑制免疫应激反应的作用.

  4. The influence of drinking-water pollution with heavy metal on the expression of IL-4 and IFN-γ in mice by real-time polymerase chain reaction.

    Science.gov (United States)

    Radbin, Rayhaneh; Vahedi, Fatemeh; Chamani, JamshidKhan

    2014-10-01

    In recent years, water pollution has been converted to a challenging discussion in health area of human being. Heavy elements are one of the most important water pollutants and their negative adverse effects on body systems have been confirmed. In this study, investigation of effects of two heavy elements including lead (Pb) and copper (Cu) on expression of interlukin-4 (IL-4) and interferon-gamma (IFN-γ) as humoral and cellular immunity biomarkers, respectively, was aimed and PCR, real-time PCR and electrophoresis techniques were used. In this study, BALB/c mice were studied that had free access to drinking water which contained Cu or Pb salts. After 2 weeks, spleens of mice were removed, RNA extracted, and cDNA was prepared for RT-PCR. Then the expression of IL-4 and IFN-γ genes were assessed by real-time PCR. The expression of IFN-γ was up-regulated in both treated groups and the expression of IL-4 was only up-regulated in the group treated with Cu and down-regulated in the group treated with Pb. This study shows that the presence of heavy elements as drinking-water pollutants results in a disproportion of natural cytokines balances, and thus may result in a negative effect on immune system.

  5. A Recombinant DNA Plasmid Encoding the sIL-4R-NAP Fusion Protein Suppress Airway Inflammation in an OVA-Induced Mouse Model of Asthma.

    Science.gov (United States)

    Liu, Xin; Fu, Guo; Ji, Zhenyu; Huang, Xiabing; Ding, Cong; Jiang, Hui; Wang, Xiaolong; Du, Mingxuan; Wang, Ting; Kang, Qiaozhen

    2016-08-01

    Asthma is a chronic inflammatory airway disease. It was prevalently perceived that Th2 cells played the crucial role in asthma pathogenesis, which has been identified as the important target for anti-asthma therapy. The soluble IL-4 receptor (sIL-4R), which is the decoy receptor for Th2 cytokine IL-4, has been reported to be effective in treating asthma in phase I/II clinical trail. To develop more efficacious anti-asthma agent, we attempt to test whether the Helicobacter pylori neutrophil-activating protein (HP-NAP), a novel TLR2 agonist, would enhance the efficacy of sIL-4R in anti-asthma therapy. In our work, we constructed a pcDNA3.1-sIL-4R-NAP plasmid, named PSN, encoding fusion protein of murine sIL-4R and HP-NAP. PSN significantly inhibited airway inflammation, decreased the serum OVA-specific IgE levels and remodeled the Th1/Th2 balance. Notably, PSN is more effective on anti-asthma therapy comparing with plasmid only expressing sIL-4R.

  6. NK-derived IFN-γ/IL-4 triggers the sexually disparate polarization of macrophages in CVB3-induced myocarditis.

    Science.gov (United States)

    Liu, Li; Yue, Yan; Xiong, Sidong

    2014-11-01

    Coxsackievirus B3 (CVB3) is a common etiology of myocarditis with an increased morbidity and mortality in males. We previously reported that differential polarization of macrophages contributed to sexually dimorphic susceptibility of mice to CVB3-induced myocarditis. However, the underlying kinetics, impetus as well as the molecular mechanism remain unclear. Here, we demonstrated that myocardial macrophages started to polarize at as early as day 5 post CVB3 infection in both genders of BALB/c mice, with M1 phenotype detected in males and M2a phenotype in females, and this trend was further amplified at day 7 when myocarditis reached peak. In addition, we identified that prevailed IFN-γ in males and dominant IL-4 in females were critical myocardial cytokines for the disparate macrophage polarization, which respectively activated JAK1-STAT1 and JAK3-STAT6 pathways. Strikingly, we found that the main source of IFN-γ and IL-4 cytokines in both genders were myocardial infiltrating NK cells, which differentially secreted cytokines in various microenvironments manifested synergistically by sex hormones and CVB3 infection. Consistently, depletion of NK cells significantly impeded the myocardial macrophage polarization in both genders of CVB3-infected mice. Collectively, these data indicated that myocardial NK-derived IFN-γ/IL-4 was critical for the differential polarization of macrophages in CVB3-induced myocarditis via activating JAK1-STAT1 and JAK3-STAT6 pathways respectively. Our study may help understand the mechanism of sexually differential polarization of macrophages and provide clues for the gender bias in CVB3-induced myocarditis.

  7. Airway responsiveness in two inbred strains of mouse disparate in IgE and IL-4 production.

    Science.gov (United States)

    Fan, T; Yang, M; Halayko, A; Mohapatra, S S; Stephens, N L

    1997-08-01

    The mouse provides an excellent model for genetic studies of asthma, which is characterized by airway hyperexcitability and hyperreactivity. The former is a function of the properties of the membrane of the airway smooth muscle (ASM), whereas the latter is a function, albeit indirectly, of the mechanical properties of the muscle contractile apparatus. The very small size of the muscle has in the past hampered its study. We report herein that contractile properties of tracheal smooth muscle (TSM) can be measured in mice. We examined TSM strips from two inbred strains of mouse, ASW and SJL, which are high and low IgE responders, respectively. Force-velocity relationships were measured in four groups of mice, two ASW (control and sensitized)/and two SJL (control and sensitized). Muscle strips from sensitized SJL mice exhibited shortening velocities (V0) and maximum shortening capacities (deltaLmax), that were significantly greater than those of the other groups. However, no difference was found between the two strains in maximal isometric force (P0). The two strains also showed differences in their potential to express cytokines such as interleukin-4 (IL-4) and IL-5 in ex vivo splenocyte cultures, as measured by the cytokines' messenger RNA (mRNA) and protein expression. The SJL strain, which exhibited TSM hyperreactivity, was found to produce significantly greater amounts of IL-4 than the ASW strain. We conclude that the altered contractile properties of TSM in sensitized SJL mice are independent of IgE response, but linked to increased amounts of IL-4.

  8. Genetic regulation of parasite infection: empirical evidence of the functional significance of an IL4 gene SNP on nematode infections in wild primates

    Directory of Open Access Journals (Sweden)

    Kappeler Peter M

    2011-04-01

    Full Text Available Abstract Background Susceptibility to parasite infection affects fitness-related processes, such as mate choice and survival, yet its genetic regulation remains poorly understood. Interleukin-4 (IL4 plays a central role in the humoral immune defence against nematode parasite infections, inducing IgE switch and regulation of worm expulsion from the intestines. The evolutionary and functional significance of single nucleotide polymorphisms (SNPs in IL4-genes is known, yet empirical information on the effect of IL4 SNPs on gastro-intestinal infections is lacking. Using samples from a population of wild red-fronted lemurs (Eulemur fulvus rufus, Primates: Lemuridae, from western Madagascar, we explored the association of IL4-gene promoter polymorphisms with nematode infections and investigated a possible functional role of the IL4 polymorphism on male reproductive success. Results Using sequence analyses of lemur DNA we detected a new SNP in the IL4 gene promoter area. Carriers of the genotype T/T showed higher nematode infection intensities than individuals of genotypes C/T and C/C. Genetic population analyses using data from more than 10 years, suggested higher reproductive success of T/T males than expected. Conclusions Our results suggest a regulatory effect of an IL4 gene promoter polymorphism on the intensity of parasite infections in a natural population of red-fronted lemurs, with a seemingly disadvantageous genotype represented in low frequencies. Long-term population analyses, however, point in the direction of a negative frequency-dependent association, giving a fitness advantage to the rare genotype. Due to low frequencies of the genotype in question conclusive evidence of a functional role of IL4 polymorphism cannot be drawn here; still, we suggest the use of IL4 polymorphism as a new molecular tool for quick assessment of individual genetic constitution with regard to nematode infection intensities, contributing to a better

  9. Early IL-4 gene expression in abomasum is associated with resistance to Haemonchus contortus in hair and wool sheep breeds.

    Science.gov (United States)

    Jacobs, J R; Sommers, K N; Zajac, A M; Notter, D R; Bowdridge, S A

    2016-06-01

    Early immune events associated with reduced larval burden remain unclear in parasite-resistant breeds of sheep. Therefore, our objective was to determine breed differences in immune-related gene expression following infection with H. contortus. Gene expression in abomasal tissue and mucosa and in abomasal lymph nodes (ALN) was measured in 24 St. Croix (hair) lambs and 24 Dorset x (Finn-Rambouillet) (wool) lambs at 0 (uninfected), 3, 5 and 7 days after infection with 10 000 L3 H. contortus larvae. Expression of IL-4 in abomasal mucosa was detected on day 3 and increased to day 7 in hair lambs, but was not detectable in wool lambs. Genes that recruit neutrophils (CXCL1) and macrophages (MCP1) were upregulated in abomasal mucosa of hair lambs. Genes associated with alternative macrophage activation (ARG-1) and eosinophil activation (Gal-14) were also upregulated in the abomasal mucosa of hair lambs. Tissue remodeling genes (MMP13, PDGF) and tumour necrosis factor alpha (TNF-α) and MCP1 were upregulated in abomasal tissue of wool lambs; these lambs also had greater expression of forkhead box P3 in ALN. These data indicate a role for early IL-4 expression locally and demonstrate potential downregulation of immunity in wool sheep that could facilitate establishment of H. contortus.

  10. 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.

  11. [The serum level transformation of IFN-gamma, IL-4 and IgE before and after SIT in patients with allergic rhinitis].

    Science.gov (United States)

    Li, Yujin; Li, Peizhong

    2013-04-01

    To assess the efficacy and the transformation of IFN-gamma, IL-4, total IgE and specific IgE before and after specific immune therapy(SIT) in patients with allergic rhinitis. The subjective symptom and levels of IFN-gamma, IL-4, total IgE and specific IgE were observed in 40 patients with allergic rhinitis before and after SIT. Total effective rate in patients after SIT was 85%. There's no significant difference between the levels of specific IgE before and after SIT(P>0.05) ,while the levels of IL-4 and total IgE were significantly lower, the levels of IFN-gamma were significantly higher pre than that of post SIT. SIT is safe and effective,and can regulate the levels of IFN-gamma, IgE and IL-4. But the role of specific IgE in SIT is still unknown.

  12. 早期梅毒患者血清中IL-2、IL-4的检测%Detection of IL-2 IL-4 in early phase of syphilis

    Institute of Scientific and Technical Information of China (English)

    陈宏翔; 盛晚香; 宋继权; 孙祥银; 宋韬

    2002-01-01

    @@ 梅毒(syphilis)是由苍白螺旋体(Treponema,pallidum,TP)感染所致的一种慢性传染病,主要通过性接触传染.其临床表现多种多样、免疫机制非常复杂,为了探讨细胞因子在梅毒发病中所起的作用,本文通过对一期和二期梅毒抗心磷脂抗体、抗梅毒螺旋体抗体、IL-2、IL-4等细胞、体液免疫相关因素的检测和比较,来探讨早期梅毒患者免疫学的变化.

  13. Incomplete deletion of IL-4Rα by LysM(Cre reveals distinct subsets of M2 macrophages controlling inflammation and fibrosis in chronic schistosomiasis.

    Directory of Open Access Journals (Sweden)

    Kevin M Vannella

    2014-09-01

    Full Text Available Mice expressing a Cre recombinase from the lysozyme M-encoding locus (Lyz2 have been widely used to dissect gene function in macrophages and neutrophils. Here, we show that while naïve resident tissue macrophages from IL-4Rαf(lox/deltaLysM(Cre mice almost completely lose IL-4Rα function, a large fraction of macrophages elicited by sterile inflammatory stimuli, Schistosoma mansoni eggs, or S. mansoni infection, fail to excise Il4rα. These F4/80(hiCD11b(hi macrophages, in contrast to resident tissue macrophages, express lower levels of Lyz2 explaining why this population resists LysM(Cre-mediated deletion. We show that in response to IL-4 and IL-13, Lyz2(loIL-4Rα(+ macrophages differentiate into an arginase 1-expressing alternatively-activated macrophage (AAM population, which slows the development of lethal fibrosis in schistosomiasis. In contrast, we identified Lyz2(hiIL-4Rα(+ macrophages as the key subset of AAMs mediating the downmodulation of granulomatous inflammation in chronic schistosomiasis. Our observations reveal a limitation on using a LysMCre mouse model to study gene function in inflammatory settings, but we utilize this limitation as a means to demonstrate that distinct populations of alternatively activated macrophages control inflammation and fibrosis in chronic schistosomiasis.

  14. Incomplete deletion of IL-4Rα by LysM(Cre) reveals distinct subsets of M2 macrophages controlling inflammation and fibrosis in chronic schistosomiasis.

    Science.gov (United States)

    Vannella, Kevin M; Barron, Luke; Borthwick, Lee A; Kindrachuk, Kristen N; Narasimhan, Prakash Babu; Hart, Kevin M; Thompson, Robert W; White, Sandra; Cheever, Allen W; Ramalingam, Thirumalai R; Wynn, Thomas A

    2014-09-01

    Mice expressing a Cre recombinase from the lysozyme M-encoding locus (Lyz2) have been widely used to dissect gene function in macrophages and neutrophils. Here, we show that while naïve resident tissue macrophages from IL-4Rαf(lox/delta)LysM(Cre) mice almost completely lose IL-4Rα function, a large fraction of macrophages elicited by sterile inflammatory stimuli, Schistosoma mansoni eggs, or S. mansoni infection, fail to excise Il4rα. These F4/80(hi)CD11b(hi) macrophages, in contrast to resident tissue macrophages, express lower levels of Lyz2 explaining why this population resists LysM(Cre)-mediated deletion. We show that in response to IL-4 and IL-13, Lyz2(lo)IL-4Rα(+) macrophages differentiate into an arginase 1-expressing alternatively-activated macrophage (AAM) population, which slows the development of lethal fibrosis in schistosomiasis. In contrast, we identified Lyz2(hi)IL-4Rα(+) macrophages as the key subset of AAMs mediating the downmodulation of granulomatous inflammation in chronic schistosomiasis. Our observations reveal a limitation on using a LysMCre mouse model to study gene function in inflammatory settings, but we utilize this limitation as a means to demonstrate that distinct populations of alternatively activated macrophages control inflammation and fibrosis in chronic schistosomiasis.

  15. Exogenous IL-4-Expressing Bone Marrow Mesenchymal Stem Cells for the Treatment of Autoimmune Sensorineural Hearing Loss in a Guinea Pig Model

    Directory of Open Access Journals (Sweden)

    Chang-qiang Tan

    2014-01-01

    Full Text Available Bone marrow mesenchymal stem cells (BMSCs expressing recombinant IL-4 have the potential to remediate inflammatory diseases. We thus investigated whether BMSCs expressing exogenous IL-4 could alleviate autoimmune sensorineural hearing loss. BMSCs isolated from guinea pigs were transfected with recombinant lentivirus expressing IL-4. A total of 33 animals were divided into three groups. Group A received scala tympani injection of IL-4-expressing BMSCs, and Group B received control vector-expressing BMSCs, and Group C received phosphate-buffered saline. The distribution of implanted BMSCs in the inner ears was assessed by immunohistochemistry and fluorescence microscopy. Auditory brain-stem response (ABR was monitored to evaluate the auditory changes. Following BMSCs transplantation, the threshold levels of ABR wave III decreased in Groups A and B and significant differences were observed between these two groups P<0.05. Transplanted BMSCs distributed in the scala tympani and scala vestibuli. In some ears with hearing loss, there was a decrease in the number of spiral ganglion cells and varying degrees of endolymphatic hydrops or floccule. Following transplantation, the lentivirus-infected BMSCs migrated to the inner ear and produced IL-4. Our results demonstrate that, upon transplantation, BMSCs and BMSCs expressing recombinant IL-4 have the ability to remediate the inflammatory injury in autoimmune inner ear diseases.

  16. Co-stimulation of cultured peripheral blood mononuclear cells from intrinsic asthmatics with exogenous recombinant IL-6 produce high levels of IL-4-dependent IgE.

    Science.gov (United States)

    Sánchez-Guerrero, I M; Herrero, N; Muro, M; Vegara, R P; Campos, M; García-Alonso, A M; Alvarez, M R

    1997-09-01

    Asthma is an inflammatory airway disorder, traditionally subdivided into extrinsic, immunoglobulin E (IgE)-mediated, and intrinsic asthma of unknown aetiology. IgE synthesis requires contact between T- and B-cells and a signal provided by interleukin (IL)-4, which can be modulated by IL-6. The objective of this study was to evaluate the effects of IL-4 and IL-6 on total IgE synthesis by peripheral blood mononuclear cells from intrinsic and extrinsic asthmatics. Peripheral blood mononuclear cells from intrinsic and extrinsic asthmatic patients and from healthy subjects were cultured and stimulated with pokeweed mitogen, recombinant IL-4 and IL-6. The IgE level in serum and supernatants was measured by an enzyme-linked immunoassay. Serum IgE was significantly lower in intrinsic asthma than in extrinsic asthma, but significantly higher than in control subjects. IgE production by cultured mononuclear cells from extrinsic asthmatics was not modified after exogenous IL-4 and IL-6 addition. However, intrinsic asthmatics showed enhancement of IgE synthesis in response to IL-4 stimulation, reaching a threefold increase of the spontaneous IgE values, when simultaneous recombinant IL-4 plus IL-6 stimulus was used. Our results indicate that exogenous recombinant interleukin-6 can significantly upregulate the interleukin-4-dependent immunoglobulin E synthesis in intrinsic asthma. This suggests that immunoglobulin E could also play a role in the pathogenesis of intrinsic asthma, in which an interleukin-6 threshold would be critical.

  17. 茶碱对哮喘患者IL-4及IgE合成的抑制作用%A study of the Inhibiting Function of theophylline on Asthma Patients by Observing the levels of IL-4 and IgE

    Institute of Scientific and Technical Information of China (English)

    刘伟; 李太华; 张洪宇

    2002-01-01

    观察了茶碱对哮喘患者外周血单个核细胞(PBMC)合成白介素-4(IL-4)和免疫球蛋白E(IgE)的抑制作用.方法用ELSa法测定IL-4、IgE含量证明,哮喘1组合成IL-4、IgE较对照组(仅用PHA)明显增高(P<0.01).哮喘2组(PHA+氨茶碱)PBMC合成IL-4、IgE较哮喘1组显著下降(P<0.05).结论认为茶碱治疗哮喘的机理,部分是通过减少IL-4、IgE的合成而达到抗炎目的.

  18. Associations between the IL-4 -590 T allele and Plasmodium falciparum infection prevalence in asymptomatic Fulani of Mali.

    Science.gov (United States)

    Vafa, Manijeh; Maiga, Bakary; Berzins, Klavs; Hayano, Masashi; Bereczky, Sandor; Dolo, Amagana; Daou, Modibo; Arama, Charles; Kouriba, Bourema; Färnert, Anna; Doumbo, Ogobara K; Troye-Blomberg, Marita

    2007-07-01

    In this study, we compared the genotype and allele frequencies of the IL-10 -1087 A/G and IL-4 -590 C/T single nucleotide polymorphisms in asymptomatic subjects of two sympatric ethnic tribes differing in susceptibility to malaria, the Fulani and the Dogon in Mali. The genotype data was correlated with ethnicity and malariometric indexes. A statistically significant inter-ethnic difference in allele and genotype frequency for both loci was noted (PDogon. Inter-ethnic differences in spleen rates, higher in the Fulani than the Dogon, were seen between T carriers (TT and CT) of both groups (PDogon. No associations between IL-10 genotypes and studied malariometric indexes were observed in any of the two communities.

  19. Biomedical Information Extraction: Mining Disease Associated Genes from Literature

    Science.gov (United States)

    Huang, Zhong

    2014-01-01

    Disease associated gene discovery is a critical step to realize the future of personalized medicine. However empirical and clinical validation of disease associated genes are time consuming and expensive. In silico discovery of disease associated genes from literature is therefore becoming the first essential step for biomarker discovery to…

  20. Biomedical Information Extraction: Mining Disease Associated Genes from Literature

    Science.gov (United States)

    Huang, Zhong

    2014-01-01

    Disease associated gene discovery is a critical step to realize the future of personalized medicine. However empirical and clinical validation of disease associated genes are time consuming and expensive. In silico discovery of disease associated genes from literature is therefore becoming the first essential step for biomarker discovery to…

  1. CD8+ T Cells Mediate Female-Dominant IL-4 Production and Airway Inflammation in Allergic Asthma.

    Directory of Open Access Journals (Sweden)

    Chihiro Ito

    Full Text Available The prevalence and severity of bronchial asthma are higher in females than in males after puberty. Although antigen-specific CD8+ T cells play an important role in the development of asthma through their suppressive effect on cytokine production, the contribution of CD8+ T cells to sex differences in asthmatic responses remains unclear. In the present study, we investigated the sex-specific effect of CD8+ T cells in the suppression of asthma using an ovalbumin mouse model of asthma. The number of inflammatory cells in bronchoalveolar lavage (BAL fluid, lung type 2 T-helper cytokine levels, and interleukin-4 (IL-4 production by bronchial lymph node cells were significantly higher in female wild-type (WT mice compared with male mice, whereas no such sex differences were observed between male and female cd8α-disrupted mice. The adaptive transfer of male, but not female, CD8+ T cells reduced the number of inflammatory cells in the recovered BAL fluid of male recipient mice, while no such sex difference in the suppressive activity of CD8+ T cells was observed in female recipient mice. Male CD8+ T cells produced higher levels of IFN-γ than female CD8+ T cells did, and this trend was associated with reduced IL-4 production by male, but not female, CD4+ T cells. Interestingly, IFN-γ receptor expression on CD4+ T cells was significantly lower in female mice than in male mice. These results suggest that female-dominant asthmatic responses are orchestrated by the reduced production of IFN-γ by CD8+ T cells and the lower expression of IFN-γ receptor on CD4+ T cells in females compared with males.

  2. ASSOCIATION OF IL-1β, IL-4 AND IL-6 GENES POLYMORPHISMS WITH GENETIC PREDISPOSITION FOR AUTOIMMUNE THYROIDITIS

    Directory of Open Access Journals (Sweden)

    E. M. Biktagirova

    2011-01-01

    Full Text Available Abstract.  Autoimmune  thyroiditis  (Hashimoto’s  thyroiditis,  HT  still  represents  an  unresolved  problem of modern endocrinology, since its etiology and pathogenesis are yet unclear. Cytokines play an important role in the regulation of immune and inflammatory response, therefore, some gene variants encoding them, are considered as potential risk risk factors for autoimmune thyroid diseases. We have genotyped 298 women from the Republic of Tatarstan (RT, control group, 137 persons; HT patients, 161 for the following gene polymorphisms: interleukin-1 beta (IL-1β +3953 C/T (rs 1143634; interleukin 4 (IL-4 -590C/T (rs 2243250, and interleukin 6 (IL-6 -174C/G (rs 1800795, using allele-specific PCR. The results showed a significantly increased frequencies of C allele (P  = 0.0003 and CT genotype (P  = 0.048, OR  = 6.05, 95%CI 2.59-2.97 of  +3953  C/T  of  IL-1β  in  patients  with  Hashimoto's thyroiditis, as compared with control group. The latter  group showed higher prevalence of T allele (P  = 0.0003 and TT genotype (P  = 4.95 Ч 6.10; OR  = 0.15, 95%CI 0.06-0.38. The 590C/T and -174C/G polymorphic variants in, resp., IL-4 and IL-6 genes are not associated with increased risk of this disease among women from RT. (Med. Immunol., 2011, vol. 13, N 6, pp 603-608 

  3. IL-17A contributes to reducing IFN-γ/IL-4 ratio and persistence of Entamoeba histolytica during intestinal amebiasis.

    Science.gov (United States)

    Deloer, Sharmina; Nakamura, Risa; Kikuchi, Mihoko; Moriyasu, Taeko; Kalenda, Yombo Dan Justin; Mohammed, Eman Sayed; Senba, Masachika; Iwakura, Yoichiro; Yoshida, Hiroki; Hamano, Shinjiro

    2017-09-16

    Amebiasis is an infectious disease caused by Entamoeba histolytica, an anaerobic protozoan parasite, and is a major public health problem worldwide, particularly in areas with inadequate sanitation and poor hygiene. Th1 responses, represented by interferon gamma (IFN-γ), play a protective role by clearing the amebae from the gut, whereas Th2 responses are responsible for chronic infection. Th17 responses preconditioned by vaccination or by modulating the intestinal microbiome protect mice from the settlement of E. histolytica. However, the role of interleukin-17A (IL-17A), which is upregulated during the natural course of intestinal amebiasis, has not been clarified. The aim of this study was to investigate the role of IL-17A during intestinal amebiasis in a mouse model. IL-17A knockout and wild-type CBA/J mice were challenged intracecally with 2×10(6)E. histolytica trophozoites, and their infection, pathology, and immune responses were monitored. Neither the initial settlement of E. histolytica nor the inflammation of the cecum was affected by the absence of IL-17A for week 1, but the infection rate and parasite burden declined in a late stage of infection, accompanied by an increased IFN-γ/IL-4 ratio. Therefore, IL-17A contributes to the persistence of E. histolytica and modulates the immune response, including the IFN-γ/IL-4 ratio, which may be responsible for the reduction of the parasite burden in the IL-17A knockout mice during the chronic phase of intestinal amebiasis. Copyright © 2017. Published by Elsevier B.V.

  4. Effects of IL-4 and IL-13 on adenosine receptor expression and responsiveness of the human mast cell line 1

    NARCIS (Netherlands)

    Versluis, Mieke; Postma, Dirkje S.; Timens, Wim; Hylkema, Machteld N.

    2008-01-01

    Background: Inhalation of adenosine-5'-monophosphate (AMP) causes bronchoconstriction in asthma but not in healthy subjects. Bronchoconstriction upon AMP inhalation is thought to occur by histamine release and subsequent binding to receptors on airway smooth muscle cells. Methods: To explain enhance

  5. 儿童支气管哮喘血清IL-4、IL-13及IgE水平变化的意义

    Institute of Scientific and Technical Information of China (English)

    蒋群芳

    2013-01-01

    目的 探讨儿童支气管哮喘急性发作期、缓解期白细胞介素4(IL-4)、白细胞介素13(IL-13)及免疫球蛋白E(IgE)水平的变化意义.方法 应用ELISA法分别测定50例哮喘儿童急性发作期、缓解期IL-4、IL-13及IgE的水平,并设健康对照组45例.结果 哮喘儿童血清IL-4、IL 13及IgE水平明显高于健康对照组,差异均有统计学意义(P<0.05).结论 IL-4、IL-13及IgE是儿童哮喘发作的重要因子,同时检测IL-4、IL-13及IgE可作为儿童哮喘辅助诊断的重要指标之一.

  6. 胃癌患者血清中 IL-2,IL-4和 IL-6的动态分析及临床意义

    Institute of Scientific and Technical Information of China (English)

    孙景春; 李锐

    2013-01-01

    目的:探讨胃癌患者血清中 IL-2,IL-4和 IL-6的动态变化及临床意义;方法:应用 ELISA 的方法检测手术前后胃癌患者血清中 IL-2, IL-4和 IL-6的水平,并与良性肿瘤患者和健康体检者(对照组)进行比较.结果:胃癌患者在手术前,IL-4和 IL-6的水平高于良性肿瘤组和对照组(P<0.05),IL-2的水平低于良性肿瘤组和对照组(P<0.05);而在手术后 IL-4和 IL-6的水平明显降低,IL-2的水平呈现升高趋势,与对照组水平接近.结论:胃癌病人存在免疫功能的紊乱,IL-2,IL-4和 IL-6的水平变化参与了胃癌的发生、发展过程,对胃癌患者的诊断和预后判断具有重要的指导意义.

  7. Effect of TGF-β1 on the Expression of IL-12, IL-15, IL-18, IL-4 and IL-10 in Heart Transplantation Rejection in Rats

    Institute of Scientific and Technical Information of China (English)

    ZHAO Jinping; LI Ping; GAO Sihai; WANG Xianguo; GAO Xiaojian

    2007-01-01

    To investigate the effect of TGF-β1 on the expressions of IL-12, IL-15, IL-18, IL-4 and IL-10 in heart transplantation rejection in rats, a model of rat cervical heterotopic heart transplanta-tion was set up and the model rats were randomly divided into three groups: control group, transplant group and TGF-β1 group. The mRNA expression levels of IL-12, IL-15, IL-18, IL-4 and IL-10 were determined by RT-PCR at the 5th day after the transplantation. The mRNA expression levels of IL-12,IL-15, IL-18 were increased obviously and those of IL-4, IL-10 were significantly decreased in the transplant group as compared with the control group (P<0.01). In the TGF-β1 group, the mRNA ex-pression levels of IL-12, IL-15, IL-18 were significantly decreased and those of IL-4, IL-10 were sig-nificantly increased as compared with the transplant group (P<0.01). The immunosuppressive effect of TGF-β1 on heart transplantation rejection was related to its inhibition of the expressions of Th1-type cytokines (IL-12, IL-15, IL-18 etc) and its promotion of the expressions of Th2-tpye cyto-kines (IL-4, IL-10).

  8. LDAP: a web server for lncRNA-disease association prediction.

    Science.gov (United States)

    Lan, Wei; Li, Min; Zhao, Kaijie; Liu, Jin; Wu, Fang-Xiang; Pan, Yi; Wang, Jianxin

    2017-02-01

    Increasing evidences have demonstrated that long noncoding RNAs (lncRNAs) play important roles in many human diseases. Therefore, predicting novel lncRNA-disease associations would contribute to dissect the complex mechanisms of disease pathogenesis. Some computational methods have been developed to infer lncRNA-disease associations. However, most of these methods infer lncRNA-disease associations only based on single data resource. In this paper, we propose a new computational method to predict lncRNA-disease associations by integrating multiple biological data resources. Then, we implement this method as a web server for lncRNA-disease association prediction (LDAP). The input of the LDAP server is the lncRNA sequence. The LDAP predicts potential lncRNA-disease associations by using a bagging SVM classifier based on lncRNA similarity and disease similarity. The web server is available at http://bioinformatics.csu.edu.cn/ldap jxwang@mail.csu.edu.cn. Supplementary data are available at Bioinformatics online.

  9. The detection of peripheral blood IL-13,IL-4 and eosinophil cells count in atopic dermatitis patients%过敏性皮炎患者外周血IL-13、IL-4和嗜酸性粒细胞数检测

    Institute of Scientific and Technical Information of China (English)

    曲松本; 宋松山; 阎丽平; 牟晓峰

    2013-01-01

    Objective:To investigate the correlation of PBEC, IL-4, IL-13 and atopic dermatitis. Methods:The counting of peripheral blood eosinophil cells (PBEC) was performed by the routine method,and the level of serum IL-4 and IL-13 in 28 atopic dermatitis patients and 40 health adults was measured by ELISA.Results:The amount of PBEC ,the level of serum IL-4 and IL-13 in atopic dermatitis group was significantly higher than that in the health control (P<0.01) , and there was a positive correlation between IL-4 and IL-13 in atopic dermatitis group(P<0.05). Conclusions:There is an important role of PBEC, IL-4 and IL-13 in atopic dermatitis, and IL-13 IL-13 May play a role by IL-4.%目的:探讨外周血中嗜酸性粒细胞(peripheral blood eosinophil ce11, PBEC)计数、人白介素-13(interleukin-13,IL-13)和人白介素-4(interleukin-4,IL-4)水平的表达在过敏性皮炎发生发展中的作用。方法:收集28例过敏性皮炎患者和40例健康查体者外周血标本,常规计数PBEC,并通过半定量酶联免疫吸附试验(ELISA)检测上述标本中的IL-13和IL-4的水平,采用t检验比较其间的差异。结果:过敏性皮炎患者外周血PBEC计数、IL-13和IL-4的水平显著高于健康对照组(P<0.01),且过敏性皮炎组IL-13和IL-4水平呈显著正相关性(P<0.05)。结论:PBEC、IL-13和IL-4参与过敏性皮炎患者体内的变态反应,IL-13可能通过IL-4来发挥作用。

  10. Douchi (fermented Glycine max Merr.) alleviates atopic dermatitis-like skin lesions in NC/Nga mice by regulation of PKC and IL-4.

    Science.gov (United States)

    Jung, A-Ram; Ahn, Sang-Hyun; Park, In-Sik; Park, Sun-Young; Jeong, Seung-Il; Cheon, Jin-Hong; Kim, Kibong

    2016-10-24

    Douchi (fermented Glycine max Merr.) is produced from fermented soybeans, which is widely used in traditional herbal medicine. In this study, we investigated whether Douchi attenuates protein kinase C (PKC) and interleukin (IL)-4 response and cutaneous inflammation in Atopic dermatitis (AD)-like NC/Nga mice. To induce AD-like skin lesions, D. farinae antigen was applied to the dorsal skin of 3-week-old NC/Nga mice. After inducing AD, Douchi extract was administered 20 mg/kg daily for 3 weeks to the Douchi-treated mice group. We identified the changes of skin barrier and Th2 differentiation through PKC and IL-4 by immunohistochemistry. Douchi treatment of NC/Nga mice significantly reduced clinical scores (p < 0.01) and histological features. The levels of PKC and IL-4 were significantly reduced in the Douchi-treated group (p < 0.01). The reduction of IL-4 and PKC led to decrease of inflammatory factors such as substance P, inducible nitric oxide synthase (iNOS) and Matrix metallopeptidase 9 (MMP-9) (all p < 0.01). Douchi also down-regulated Th1 markers (IL-12, TNF-α) as well as Th2 markers (IL-4, p-IκB) (p < 0.01). Douchi alleviates AD-like skin lesions through suppressing of PKC and IL-4. These results also lead to diminish levels of substance P, iNOS and MMP-9 in skin lesions. Therefore, Douchi may have potential applications for the prevention and treatment of AD.

  11. Interaction between endothelial cells and the secreted cytokine drives the fate of an IL4- or an IL5-transduced tumour.

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    Di Carlo, E; Modesti, A; Coletti, A; Colombo, M P; Giovarelli, M; Forni, G; Diodoro, M G; Musiani, P

    1998-12-01

    Injection of interleukin-4 (IL4) gene-transduced tumour cells into syngeneic immunocompetent mice resulted in tumour rejection in which a key role for eosinophils was suggested. To evaluate whether IL5 inhibits tumour growth by selectively inducing eosinophil recruitment and activation, a poorly differentiated mammary adenocarcinoma cell line (TSA) was transfected with the IL5 gene and the cells secreting IL5 (TSA-IL5) were injected subcutaneously (s.c.) in syngeneic mice. The oncogenicity of TSA-IL5 was compared with that exhibited by TSA cells transfected with the IL4 gene (TSA-IL4) and with the neomycin resistance gene only (TSA-neo). At progressive times after subcutaneous challenge, tumour growth areas were studied histologically, ultrastructurally, and immunohistochemically to identify the reactive cells, visualize tumour vessels, and detect the cytokines and chemokines involved in the anti-tumour reaction. Both the morphological and the functional data showed that TSA-IL5, despite the large eosinophil infiltrate, grew progressively like TSA-neo, suggesting that eosinophils per se do not play a crucial role in TSA tumour rejection. Furthermore, our data indicate that the rejection of TSA-IL4 depends on the IL4-induced expression of VCAM-1 and MCP-1 by endothelial cells. MCP-1 together with VCAM-1 results in recruitment and activation of basophils, mast cells, and macrophages, and hence a pro-inflammatory cytokine cascade that initially favours the influx and activation of neutrophils and finally tumour rejection. In this context, the rejection of TSA-IL4 seems to involve a variety of reactive cells and rests on a continuous cross-talk between basophils, mast cells, macrophages, CD8-positive lymphocytes, and granulocyte subsets, mostly neutrophils.

  12. Microglial VPAC1R mediates a novel mechanism of neuroimmune-modulation of hippocampal precursor cells via IL-4 release.

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    Nunan, Robert; Sivasathiaseelan, Harri; Khan, Damla; Zaben, Malik; Gray, William

    2014-08-01

    Neurogenesis, the production of new neurons from neural stem/progenitor cells (NSPCs), occurs throughout adulthood in the dentate gyrus of the hippocampus, where it supports learning and memory. The innate and adaptive immune systems are increasingly recognized as important modulators of hippocampal neurogenesis under both physiological and pathological conditions. However, the mechanisms by which the immune system regulates hippocampal neurogenesis are incompletely understood. In particular, the role of microglia, the brains resident immune cell is complex, as they have been reported to both positively and negatively regulate neurogenesis. Interestingly, neuronal activity can also regulate the function of the immune system. Here, we show that depleting microglia from hippocampal cultures reduces NSPC survival and proliferation. Furthermore, addition of purified hippocampal microglia, or their conditioned media, is trophic and proliferative to NSPCs. VIP, a neuropeptide released by dentate gyrus interneurons, enhances the proliferative and pro-neurogenic effect of microglia via the VPAC1 receptor. This VIP-induced enhancement is mediated by IL-4 release, which directly targets NSPCs. This demonstrates a potential neuro-immuno-neurogenic pathway, disruption of which may have significant implications in conditions where combined cognitive impairments, interneuron loss, and immune system activation occurs, such as temporal lobe epilepsy and Alzheimer's disease.

  13. IL4 gene polymorphism and previous malaria experiences manipulate anti-Plasmodium falciparum antibody isotype profiles in complicated and uncomplicated malaria

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    Kalambaheti Thareerat

    2009-12-01

    Full Text Available Abstract Background The IL4-590 gene polymorphism has been shown to be associated with elevated levels of anti-Plasmodium falciparum IgG antibodies and parasite intensity in the malaria protected Fulani of West Africa. This study aimed to investigate the possible impact of IL4-590C/T polymorphism on anti-P. falciparum IgG subclasses and IgE antibodies levels and the alteration of malaria severity in complicated and uncomplicated malaria patients with or without previous malaria experiences. Methods Anti-P.falciparum IgG subclasses and IgE antibodies in plasma of complicated and uncomplicated malaria patients with or without previous malaria experiences were analysed using ELISA. IL4-590 polymorphisms were genotyped using RFLP-PCR. Statistical analyses of the IgG subclass levels were done by Oneway ANOVA. Genotype differences were tested by Chi-squared test. Results The IL4-590T allele was significantly associated with anti-P. falciparum IgG3 antibody levels in patients with complicated (P = 0.031, but not with uncomplicated malaria (P = 0.622. Complicated malaria patients with previous malaria experiences carrying IL4-590TT genotype had significantly lower levels of anti-P. falciparum IgG3 (P = 0.0156, while uncomplicated malaria patients with previous malaria experiences carrying the same genotype had significantly higher levels (P = 0.0206 compared to their IL4-590 counterparts. The different anti-P. falciparum IgG1 and IgG3 levels among IL4 genotypes were observed. Complicated malaria patients with previous malaria experiences tended to have lower IgG3 levels in individuals carrying TT when compared to CT genotypes (P = 0.075. In contrast, complicated malaria patients without previous malaria experiences carrying CC genotype had significantly higher anti-P. falciparum IgG1 than those carrying either CT or TT genotypes (P = 0.004, P = 0.002, respectively. Conclusion The results suggest that IL4-590C or T alleles participated differently in the

  14. Chronic proliferative dermatitis in Sharpin null mice: development of an autoinflammatory disease in the absence of B and T lymphocytes and IL4/IL13 signaling.

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    Christopher S Potter

    Full Text Available SHARPIN is a key regulator of NFKB and integrin signaling. Mice lacking Sharpin develop a phenotype known as chronic proliferative dermatitis (CPDM, typified by progressive epidermal hyperplasia, apoptosis of keratinocytes, cutaneous and systemic eosinophilic inflammation, and hypoplasia of secondary lymphoid organs. Rag1(-/- mice, which lack mature B and T cells, were crossed with Sharpin(-/- mice to examine the role of lymphocytes in CDPM. Although inflammation in the lungs, liver, and joints was reduced in these double mutant mice, dermatitis was not reduced in the absence of functional lymphocytes, suggesting that lymphocytes are not primary drivers of the inflammation in the skin. Type 2 cytokine expression is increased in CPDM. In an attempt to reduce this aspect of the phenotype, Il4ra(-/- mice, unresponsive to both IL4 and IL13, were crossed with Sharpin(-/- mice. Double homozygous Sharpin(-/- , Il4ra(-/- mice developed an exacerbated granulocytic dermatitis, acute system inflammation, as well as hepatic necrosis and mineralization. High expression of CHI3L4, normally seen in CPDM skin, was abolished in Sharpin(-/- , Il4ra(-/- double mutant mice indicating the crucial role of IL4 and IL13 in the expression of this protein. Cutaneous eosinophilia persisted in Sharpin(-/- , Il4ra(-/- mice, although expression of Il5 mRNA was reduced and the expression of Ccl11 and Ccl24 was completely abolished. TSLP and IL33 were both increased in the skin of Sharpin(-/- mice and this was maintained in Sharpin(-/- , Il4ra(-/- mice suggesting a role for TSLP and IL33 in the eosinophilic dermatitis in SHARPIN-deficient mice. These studies indicate that cutaneous inflammation in SHARPIN-deficient mice is autoinflammatory in nature developing independently of B and T lymphocytes, while the systemic inflammation seen in CPDM has a strong lymphocyte-dependent component. Both the cutaneous and systemic inflammation is enhanced by loss of IL4 and IL13 signaling

  15. A FQ-RT-PCR method for quantitative determination of IL-2 mRNA and IL-4 mRNA and its application

    Institute of Scientific and Technical Information of China (English)

    QING HUI ZHU; QING LU; GU SHENG ZHANG

    2006-01-01

    The purpose of the study is to establish a fluorescence quantitative reverse transcription polymerase chain response (FQ-RT-PCR) method for the quantitative determination of IL-2 mRNA and IL-4mRNA in Th cells, with which the Th cells status of the patients with gynaecological tumors and chronic renal failure (CRF) can be analyzed. IL-2 cDNA and IL-4 cDNA were prepared, and the plasmid pMD18 carrying IL-2 cDNA or IL-4 cDNA fragment was constructed and cloned as the template for quantitative determination. The primers and probes labelled with 6-carboxy-fluorescein (FAM) and 6-carboxytetramethylrhodamine (TAMRA) were prepared, and the experimental conditions were optimized to set up the FQ-RT-PCR method for quantitative determination of IL-2 mRNA and IL-4 mRNA. Th cells enriched from peripheral blood mononuclear cells (PBMCs) of 20 healthy volunteers (HVs), 16 gynaecological benign (GB) cases, 18 gynaecological malignant (GM) tumor cases and 16 chronic renal failure (CRF) patients were tested for IL-2 mRNA and IL-4 mRNA by FQ-RT-PCR. The house-keeping gene 3-actin was used as the internal control gene of the experiment. The standard curve for log concentration of series of quantitative templates vs threshold cycle (CT) was established by linear regression, and the linear range was 102-107 copies/μl. The imprecision test showed the CV of inter-assay and intra-assay of a high content sample by FQ-RT-PCR were 7.8% and 12.5%, respectively. The CV of inter-assay and intra-assay of a low content sample were 10.8% and 19.5%, respectively. The IL-2 mRNA expressions in Th of the patients with gynaecological malignant tumor (compared with the HVs and the patients with gynaecological benign disease) and in Th of the CRF patients (compared with the HVs) were declined significantly and at the same time the IL-4 mRNA expression increased significantly ( P < 0. 001 ). A simple, sensitive and accurate FQ-RT-PCR method for the quantitative detection of IL-2 mRNA and IL-4 mRNA has

  16. Novel HIV IL-4R antagonist vaccine strategy can induce both high avidity CD8 T and B cell immunity with greater protective efficacy.

    Science.gov (United States)

    Jackson, Ronald J; Worley, Matthew; Trivedi, Shubhanshi; Ranasinghe, Charani

    2014-09-29

    We have established that the efficacy of a heterologous poxvirus vectored HIV vaccine, fowlpox virus (FPV)-HIV gag/pol prime followed by attenuated vaccinia virus (VV)-HIV gag/pol booster immunisation, is strongly influenced by the cytokine milieu at the priming vaccination site, with endogenous IL-13 detrimental to the quality of the HIV specific CD8+ T cell response induced. We have now developed a novel HIV vaccine that co-expresses a C-terminal deletion mutant of the mouse IL-4, deleted for the essential tyrosine (Y119) required for signalling. In our vaccine system, the mutant IL-4C118 can bind to IL-4 type I and II receptors with high affinity, and transiently prevent the signalling of both IL-4 and IL-13 at the vaccination site. When this IL-4C118 adjuvanted vaccine was used in an intranasal rFPV/intramuscular rVV prime-boost immunisation strategy, greatly enhanced mucosal/systemic HIV specific CD8+ T cells with higher functional avidity, expressing IFN-γ, TNF-α and IL-2 and greater protective efficacy were detected. Surprisingly, the IL-4C118 adjuvanted vaccines also induced robust long-lived HIV gag-specific serum antibody responses, specifically IgG1 and IgG2a. The p55-gag IgG2a responses induced were of a higher magnitude relative to the IL-13Rα2 adjuvant vaccine. More interestingly, our recently tested IL-13Rα2 adjuvanted vaccine which only inhibited IL-13 activity, even though induced excellent high avidity HIV-specific CD8+ T cells, had a detrimental impact on the induction of gag-specific IgG2a antibody immunity. Our observations suggest that (i) IL-4 cell-signalling in the absence of IL-13 retarded gag-specific antibody isotype class switching, or (ii) IL-13Rα2 signalling was involved in inducing good gag-specific B cell immunity. Thus, we believe our novel IL-4R antagonist adjuvant strategy offers great promise not only for HIV-1 vaccines, but also against a range of chronic infections where sustained high quality mucosal and systemic T and B

  17. 首发精神分裂症患者使用阿立哌唑后血清IL-2、IL-4水平变化的探讨%Explore the level changes of IL-2,IL-4 in the first-episode schizophrenia after the treatment of arip-iprazole

    Institute of Scientific and Technical Information of China (English)

    刘倩倩; 李亚飞; 朱祥路; 蒋天玉

    2014-01-01

    Objective To explore the differences of serum IL-2 ,IL-4 in the first-episode schizo-phrenia and healthy controls were explored ,and to compare the changes of symptoms before and after aripiprazole treatment and the changes of serum IL-2 ,IL-4 .Methods Serum of IL-2 ,IL-4 was exam-ined with Flow Cytometry in 35 healthy volunteers and 35 first episode patients .The symptoms of pa-tients were evaluated with Positive and Negative Syndrome Scale .Results There were no statistical sig-nificantly differents in the serum of IL-2 ,IL-4 in the first-episode schizophrenia than normal .controls (P>0 .05) .The serum levels of IL-4 was lower in patients with first-episode schizophrenia after aripi-prazole treatment (P<0 .01) .IL-2 and IL-4 levels were increased in positive symptoms of schizophre-nia patients before aripiprazole treatment (positive symptoms) than normal controls (P<0 .05) .IL-2 and IL-4 levels were different in positive symptoms of schizophrenia patients before and after aripi-prazole treatment (P<0 .05) .Conclusion The patients with schizophrenia have immune dysfunction ;Aripiprazole of antipsychotics have lowered the level of IL-2 ,IL-4 and positive symptoms also im-proved .Conclusion.%目的:探讨首发精神分裂症患者血清细胞因子IL-2、IL-4与正常人的差异,比较分析首发精神分裂症患者经过阿立哌唑治疗前后症状改变及细胞因子IL-2、IL-4的变化。方法选择35例首发精神分裂症患者作为研究组,35例健康志愿者作为对照组,通过流式细胞学技术测定血清标本中IL-2、IL-4的水平,用PANSS量表评定精神症状。结果(1)首发精神分裂症患者IL-2、IL-4水平与正常对照组相比,差异无统计学意义(P>0.05)。(2)首发精神分裂症患者阿立哌唑治疗后较治疗前IL-4水平降低,差异有统计学意义(P<0.01)。(3)首发精神分裂症阳性症状患者血清IL-2、IL-4水平在治疗前均高于对照组(P<0.05

  18. Study of polymorphisms in the interleukin-4 and IL-4 receptor genes in a population of Brazilian patients with multiple sclerosis Estudo de polimorfismos nos genes da interleucina-4 (*33C-T e receptor IL-4 (*Q551R numa população de pacientes brasileiros com esclerose múltipla

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    Thereza Quirico-Santos

    2007-03-01

    Full Text Available This study aimed to investigate in a population of Brazilian patients with multiple sclerosis (MS single-nucleotide polymorphisms (SNP in the promoter region of IL4 (*33C-T and receptor IL4R (*Q551R A-G genes proposed to interfere with disease progression. No significant differences were observed in either of the SNPs investigated between healthy controls (n=135 and MS patients (n=129. However, the IL4+33 TT genotype was significantly (p=0.039 higher in African descendants MS (AF-MS= 9.09% than in Caucasian MS (CA-MS= 1.35%. It was also observed a significant (p=0.016 increase for the IL4R* Q551R CC genotype in AF-MS compared to those of Caucasian ethnicity (AF-MS= 21.62%; CA-MS= 4.35%. These results suggest that IL4+33 and IL4R*Q551 polymorphisms may have a disease-promoting role of TH2 mediators in African MS descendants. Additionally neither IL4 nor IL4R genes are susceptibility factors for Brazilian MS but may be able to modify ethnicity-dependent disease risk and penetrance of susceptibility factors.Este é um estudo inédito realizado numa população brasileira de pacientes portadores de esclerose múltipla (EM visando determinar uma possível associação na expressão de polimorfismo (SNP nos genes da citocina reguladora IL4 (*33C-T e do seu respectivo receptor IL4R (*Q551R A-G capazes de modificar a evolução da doença. Não foi observada diferença significativa em ambos SNPs analisados entre o grupo controle de indivíduos saudáveis (n=135 e os pacientes com EM (n=129. Contudo, o genotipo IL4+33 TT apresentava percentual mais elevado (9,09% nos pacientes EM com descendência africana (AF-EM do que nos descendentes caucasianos (CA-EM=1,35% sendo esta diferença significativa (p=0,039. Também foi observado um aumento significativo (p=0,016 para o genotipo IL4R* Q551R CC nos pacientes AF-EM (21,62% comparando-se com CA-EM (4,35%. Estes resultados indicam que polimorfismos nos genes da citocina IL4 (*33C-T e respectivo receptor IL4R

  19. 哮喘患儿血清IL-4、IL-13及嗜酸性粒细胞意义的探讨%Exploration into Significance of Serum IL-4 and IL-13 and EOS in Children Patients

    Institute of Scientific and Technical Information of China (English)

    吴海涛

    2012-01-01

    [目的]检测哮喘患儿血清中IL-4、IL-13及嗜酸性粒细胞(EOS)的水平并探讨其临床意义.[方法]取中-量度哮喘患几28例为实验组1、缓解期哮喘患儿24例为实验组2、取正常儿童25例为对照组,分别取外周静脉血3mL,用ELISA方法检测IL-4、IL-13的含量,并进行外周血嗜酸性粒细胞计数.[结果]两实验组IL-4、IL-13、EOS计数水平均高于对照组,实验组1较实验组2明显增高;且哮喘患儿血清IL-4与IL-13水平呈正相关.[结论]IL-4、IL-13及EOS参与了哮喘的发病过程,其水平反映了病情的严重程度;且这些因子间存在着一定联系.%[ Objective ]To detect the levels of serum intcrleukin-4(IL-4),interleukin-13(IL-13) and eosinophil(EOS) in bronchial asthma children patients and investigate the clinical significance of these cytokines. [Methods] 52 children patients suffering bronchial asthma were selected as two expremental groups(EG): patients suffering moderate-severe bronchial asthma were selected as EG1 (n=28) and patients in remission of asthma as EG2 (n=24); 25 healthy children were served as the control group (CG). Venous blood was collected from every individual. The concentrations of serum IL-4 and IL-13 were measured by enzyme linked immunosorbent assay, the blood specimens were assayed for eosinophil count.[Results] Compared with the CG.the IL-4,IL-13 and EOS levels in both EGs were increased obviously, the IL-4,IL-13 and EOS levels in EG1 were increased compared with EG2.Moreover,there were positive correlation between the level of IL- 4 and IL-13. [Condution] IL-4,IL-13 and EOS participate in the pathogenethy of bronchial asthma,the levels of these cytokines indicate the severity of clinical symptom in asthma,and some connection exists among these cytokines.

  20. 黄芪有效部位对化疗性贫血小鼠细胞因子IL-2、 IL-4、 IL-6的影响%Effect of Effective Parts of Astragalus on Cytokines IL-2 IL-4and IL-6 of Chemotherapy-induced Anemic Mice

    Institute of Scientific and Technical Information of China (English)

    陈晶晶; 范颖; 张红梅; 林庶茹

    2011-01-01

    目的:探讨黄芪有效部位对化疗性贫血模型小鼠脾组织IL-2、IL-4、IL-6的影响.方法:采用ELISA 法测定脾组织IL-2、IL-4、IL-6含量.结果:模型组脾组织IL-2、IL-4含量下降,IL-6含量升高,均有统计学意义(P<0.05).各治疗组对化疗所致骨髓抑制性贫血的脾组织IL-2、IL-4、IL-6具有不同程度的调控作用.结论:IL-2、IL-4、IL-6与环磷酰胺所致骨髓抑制性贫血的免疫失调有关;黄芪及其有效部位对环磷酰胺引起的骨髓抑制性贫血引发的免疫损伤具有保护作用,并对IL-2、IL-4、IL-6的生成具有不同的调节机制.%Objective: To investigate effect of effective parts of astragalus on cytokines IL-2,IL-4 and IL-6 of chemotherapy-induced anemic mice. Methods : Enzyme-linked immunosorbent assay(ELISA) was applied to measure the content of IL-2, EL-4 and IL-6 in spleen. Results: In spleen of the model group, the content of IL-2 and IL-4 decreased, the content of IL-6 increased, both with significances in statistics(P<0.05). In each treated group, IL-2, IL-4 and IL-6 in spleen of chemotherapy-induced myelosuppression anemic mice are regulated in varying degree. Conclusion: There are relationship between immune disorders caused by cyclophosphamide-induced myelosuppression anemia and the content of IL-2, IL-4 and IL-6. Astragalus and its effective parts can protect immune injury caused by cyclophosphamide-induced myelosuppression anemia, also regulate the production of IL-2, IL-4 and IL-6 in different metabolism.

  1. 地氯雷他定对过敏性哮喘豚鼠模型肺组织IL-4R mRNA表达的影响%Effects of Desloratadine on the Expression of IL-4 Receptor mRNA in Lung Tissues of Allergic Asthma Guinea Pig

    Institute of Scientific and Technical Information of China (English)

    张丽; 白茹芹

    2015-01-01

    Objective: To study the effects of desloratadine on the expression of IL-4 receptor mRNA in lung tissues of allergic asthma guinea pig. Methods: The allergic asthma model of guinea pig was induced by ovalbumin. Then the effects of desloratadine were observed on the pathological changes and the expression of IL-4 receptor mRNA in lung tissues. ResuIts: Desloratadine could improve the pathological changes and decrease the expression of IL-4 receptor mRNA in lung tissues. ConcIusion: Decreasing the expression of IL-4 receptor mRNA in lung tissues may be the mechanism of desloratadine in treating asthma.%目的:研究地氯雷他定对过敏性哮喘豚鼠模型肺组织IL-4R mRNA表达的影响。方法:用卵蛋白制备过敏性哮喘豚鼠模型,观察地氯雷他定对过敏性哮喘豚鼠肺组织病理及IL-4R mRNA表达水平的影响。结果:地氯雷他定能显著改善过敏性哮喘豚鼠肺组织病理变化,明显降低肺组织IL-4R mRNA表达水平。结论:降低肺组织IL-4R mRNA的表达可能是地氯雷他定防治哮喘的基因机制。

  2. PROGNOSIS FOR PREDISPOSAL TO DEVELOPMENT OF VIRAL HEPATITIS C BASED ON G-308A TNFА, T-330G IL-2, С-590Т IL-4, С-703Т IL-5, AND C-592A IL-10 GENE POLYMORPHISMS

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    V. V. Avdoshina

    2006-01-01

    Full Text Available Abstract. The main objective of this work was to identify allelic variants of cytokine genes at the polymorphic positions of G-308A TNFА, T-330G IL-2, С-590Т IL-4, С-703Т IL-5, and C-592A IL-10, and to assess their contribution to predisposition and resistance of human patients to progression of viral hepatitis C infection. We observed significant increase in frequency of T/G T-330G IL-2 genotype in HCV-infected patients, as compared to healthy individuals. Distribution analysis of C-590T promoter alleles of the IL-4 gene displayed a wide overrepresentation of C/T genotype among HCV-infected patients. Likewise, we have shown the G/A genotype of G-308A TNFA to be highly frequent in the group of HCV-infected patients, whereas this genotype was rare in the sample of healthy persons. When analysing allelic frequencies of cytokine genes at these polymorphic positions, we get an opportunity to predict predisposal for the chronic variant of viral hepatitis C in HCV-infected persons.

  3. IL4I1 Is a Novel Regulator of M2 Macrophage Polarization That Can Inhibit T Cell Activation via L-Tryptophan and Arginine Depletion and IL-10 Production.

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    Yinpu Yue

    Full Text Available Interleukin 4-induced gene-1 (IL4I1 was initially described as an early IL-4-inducible gene in B cells. IL4I1 protein can inhibit T cell proliferation by releasing its enzymatic catabolite, H2O2, and this effect is associated with transient down-regulation of T cell CD3 receptor-zeta (TCRζ expression. Herein, we show that IL4I1 contributes to the regulation of macrophage programming. We found that expression of IL4I1 increased during bone marrow-derived macrophage (BMDM differentiation, expression of IL4I1 is much higher in primary macrophages than monocytes, and IL4I1 expression in BMDMs could be induced by Th1 and Th2 cytokines in two different patterns. Gene expression analysis revealed that overexpression of IL4I1 drove the expression of M2 markers (Fizz1, Arg1, YM-1, MR and inhibited the expression of M1-associated cytokines. Conversely, knockdown of IL4I1 by siRNA resulted in opposite effects, and also attenuated STAT-3 and STAT-6 phosphorylation. Furthermore, IL4I1 produced by macrophages catalyzed L-tryptophan degradation, while levo-1-methyl-tryptophan (L-1-MT, but not dextro-1-methyl-tryptophan, partially rescued IL4I1-dependent inhibition of T cell activation. Other inhibitors, such as diphenylene iodonium (DPI, an anti-IL-10Rα blocking antibody, and a nitric oxide synthase inhibitor, NG-monomethyl-L-arginine, also had this effect. Overall, our findings indicate that IL4I1 promotes an enhanced M2 functional phenotype, which is most likely associated with the phosphorylation of STAT-6 and STAT-3. Moreover, DPI, L-1-MT, NG-monomethyl-L-arginine, and anti-IL-10Rα blocking antibody were all found to be effective IL4I1 inhibitors in vitro.

  4. Significance of CYCLOOXYGENASE-2(COX-2), PERIOSTIN (POSTN) and INTERLEUKIN-4(IL-4) gene expression in the pathogenesis of chronic rhinosinusitis with nasal polyps.

    Science.gov (United States)

    Miłoński, Jarosław; Zielińska-Bliźniewska, Hanna; Przybyłowska, Karolina; Pietkiewicz, Piotr; Korzycka-Zaborowska, Barbara; Majsterek, Ireneusz; Olszewski, Jurek

    2015-12-01

    The purpose of this paper was to evaluate the level of Cyclooxygenase-2 (COX-2), Periostin (POSTN) and Interleukin-4(IL-4) gene expression in patients with chronic rhinosinusitis with nasal polyps, without polyps and with a nasal septum deviation. The tests were performed on 63 patients (24 women and 39 men) with chronic rhinosinusitis and polyps (CRSwP-study group I), with determination of the COX-2, POSTN and IL-4 gene expression; an allergy was diagnosed in 38 cases. The reference groups were patients with chronic rhinosinusitis without polyps--CRS (n = 23, including 14 women and 9 men) and patients with nasal septum deviation--DSN (n = 18, including 9 women and 9 men). The expression level was determined in the polyp tissue and the mucosa of paranasal sinus collected during an FESS. The expression level of studied genes was also evaluated in the material. Immediately after being collected, the tissue fragments were placed in test tubes with 1 ml of RNAlater (Qiagen, Hilden, Germany) preventing the degradation of RNA and frozen at -70 °C. The studies revealed an increased level of POSTN, IL-4 gene expression and a decreased level of COX-2 gene expression that may be associated with the development of chronic rhinosinusitis with nasal polyps. An analysis of the expression level indicates the participation of POSTN and IL-4 in the development of chronic rhinosinusitis with nasal polyps in patients with atopy.

  5. IL-4 Protects the Mitochondria Against TNFα and IFNγ Induced Insult During Clearance of Infection with Citrobacter rodentium and Escherichia coli.

    Science.gov (United States)

    Maiti, Arpan K; Sharba, Sinan; Navabi, Nazanin; Forsman, Huamei; Fernandez, Harvey R; Lindén, Sara K

    2015-01-01

    Citrobacter rodentium is a murine pathogen that serves as a model for enteropathogenic Escherichia coli. C. rodentium infection reduced the quantity and activity of mitochondrial respiratory complexes I and IV, as well as phosphorylation capacity, mitochondrial transmembrane potential and ATP generation at day 10, 14 and 19 post infection. Cytokine mRNA quantification showed increased levels of IFNγ, TNFα, IL-4, IL-6, and IL-12 during infection. The effects of adding these cytokines, C. rodentium and E. coli were hence elucidated using an in vitro colonic mucosa. Both infection and TNFα, individually and combined with IFNγ, decreased complex I and IV enzyme levels and mitochondrial function. However, IL-4 reversed these effects, and IL-6 protected against loss of complex IV. Both in vivo and in vitro, the dysfunction appeared caused by nitric oxide-generation, and was alleviated by an antioxidant targeting mitochondria. IFNγ -/- mice, containing a similar pathogen burden but higher IL-4 and IL-6, displayed no loss of any of the four complexes. Thus, the cytokine environment appears to be a more important determinant of mitochondrial function than direct actions of the pathogen. As IFNγ and TNFα levels increase during clearance of infection, the concomitant increase in IL-4 and IL-6 protects mitochondrial function.

  6. Rat bone marrow-derived dendritic cells generated with GM-CSF/IL-4 or FLT3L exhibit distinct phenotypical and functional characteristics.

    Science.gov (United States)

    N'diaye, Marie; Warnecke, Andreas; Flytzani, Sevasti; Abdelmagid, Nada; Ruhrmann, Sabrina; Olsson, Tomas; Jagodic, Maja; Harris, Robert A; Guerreiro-Cacais, Andre Ortlieb

    2016-03-01

    Dendritic cells are professional APCs that play a central role in the initiation of immune responses. The limited ex vivo availability of dendritic cells inspires the widespread use of bone marrow-derived dendritic cells as an alternative in research. However, the functional characteristics of bone marrow-derived dendritic cells are incompletely understood. Therefore, we compared functional and phenotypic characteristics of rat bone marrow-derived dendritic cells generated with GM-CSF/IL-4 or FLT3 ligand bone marrow-derived dendritic cells. A comparison of surface markers revealed that FLT3 ligand-bone marrow-derived dendritic cells expressed signal regulatory protein α, CD103, and CD4 and baseline levels of MHC class II, CD40, and CD86, which were highly up-regulated upon stimulation. Conversely, GM-CSF/IL-4-bone marrow-derived dendritic cells constitutively expressed signal regulatory protein α, CD11c, and CD11b but only mildly up-regulated MHC class II, CD40, or CD86 following stimulation. Expression of dendritic cell-associated core transcripts was restricted to FLT3 ligand-bone marrow-derived dendritic cells . GM-CSF/IL-4-bone marrow-derived dendritic cells were superior at phagocytosis but were outperformed by FLT3 ligand-bone marrow-derived dendritic cells at antigen presentation and T cell stimulation in vitro. Stimulated GM-CSF/IL-4-bone marrow-derived dendritic cells secreted more TNF, CCL5, CCL20, and NO, whereas FLT3 ligand-bone marrow-derived dendritic cells secreted more IL-6 and IL-12. Finally, whereas GM-CSF/IL-4-bone marrow-derived dendritic cell culture supernatants added to resting T cell cultures promoted forkhead box p3(+) regulatory T cell populations, FLT3 ligand-bone marrow-derived dendritic cell culture supernatants drove Th17 differentiation. We conclude that rat GM-CSF/IL-4-bone marrow-derived dendritic cells and FLT3 ligand-bone marrow-derived dendritic cells are functionally distinct. Our data support the current rationale that FLT3

  7. Eotaxin and IL-4 levels are increased in induced sputum and correlate with sputum eosinophils in patients with nonasthmatic eosinophilic bronchitis.

    Science.gov (United States)

    Zhang, Rui; Luo, Wei; Liang, Zhenyu; Tan, Yaxia; Chen, Ruchong; Lu, Wenju; Zhong, Nanshan

    2017-03-01

    Nonasthmatic eosinophilic bronchitis (NAEB) is characterized by chronic cough and airway eosinophilic inflammation. Airway and systemic inflammation cytokine profile have not been comprehensively described in patients with NAEB.The aim of the study was to identify the cytokine profile in sputum and serum of NAEB patients. Furthermore, the relationship between cytokines and clinical features would be evaluated.Induced sputum and serum were collected from untreated NAEB patients and healthy subjects. The cytokine profile in sputum and serum was analyzed by a bead-based multiplex cytokine assay including 21 cytokines.The levels of EGF, eotaxin, GM-CSF, GRO, IFN-γ, IL-1β, IL-4, IL-6, IL-17A, IP-10, MIP-1α, and TNF-α in sputum were significantly higher in NAEB patients than that in healthy subjects (all P < 0.05). Values of area under the receiver operating characteristic curve (AUROC) of these cytokines were all above 0.750. The concentrations of eotaxin and IL-4 were positively correlated with sputum eosinophil percentage (r = 0.726, P = 0.002; r = 0.511, P = 0.043; respectively). No significant correlations between other cytokines (EGF, GM-CSF, GRO, IFN-γ, IL-1β, IL-6, IL-17A, IP-10, MIP-1α, and TNF-α) in sputum and sputum eosinophil percentage were found. The level of IL-4 in serum was slightly higher in NAEB patients than in healthy subjects. However, there was no correlation between serum IL-4 levels and sputum eosinophil percentage.We identified the cytokine profile in sputum and serum from NAEB patients. Sputum eotaxin and IL-4 could have the potential to become the biomarkers for NAEB and might be useful to assist in the diagnosis of NAEB.

  8. 尖锐湿疣组织IL-2、IL-4、IL-10、IL-18表达的意义

    Institute of Scientific and Technical Information of China (English)

    胡凯; 程方雄; 陈蓓; 韩林; 马鸣

    2012-01-01

    目的:探讨尖锐湿疣(CA)患者治疗前、后血清中白细胞介素(IL)-2、IL-4、IL-10和IL-18的水平变化在CA免疫发病机制中的作用.方法:用酶联免疫吸附法(ELISA)分别检测30例CA患者在治疗前和治疗后3个月未复发时血清IL-2、IL-4 、ID-10和IL-18的水平,并与20例正常人作比较.结果:结果CA患者治疗前血清中IL-2水平明显低于正常对照组(P<0.01),IL-4、IL-10和IL-18水平明显高于正常对照组(P<0.05);治疗后3个月末血清IL-2、IL-4、IL-10、IL-18的水平同正常对照组相比,差异无统计学意义(均P>0.05).结论:人乳头瘤病毒(HPV)感染可造成患者细胞免疫功能异常,IL-2、IL-4、IL-10和IL 18在CA免疫发病机制中可能起重要作用.

  9. 尖锐湿疣组织IL-2、IL-4、IL-1O、IL-18的表达

    Institute of Scientific and Technical Information of China (English)

    胡凯; 程方雄; 陈蓓; 韩林; 马鸣

    2012-01-01

    目的:探讨尖锐湿疣(CA)患者治疗前、后血清中白介素2(IL-2)、白介素4(IL-4)、白介素10(IL-10)和白介素18(IL-18)的水平变化在CA免疫发病机制中的作用.方法:用酶联免疫吸附法(ELISA)分别检测30例CA患者在治疗前和治疗后3个月未复发时血清IL-2、IL-4、IL-10和IL-18的水平,并与20例正常人作比较.结果:CA患者治疗前血清中IL2水平明显低于正常对照组(P>0.01),IL-4、IL-10和IL-18水平明显高于正常对照组(P>0.05);治疗后3个月末血清IL-2、IL-4、IL-10、IL-18的水平同正常对照组相比,差异无统计学意义(P均>0.05).结论:人乳头瘤病毒(HPV)感染可造成患者细胞免疫功能异常,IL2、IL-4、IL-10和IL-18在CA免疫发病机制中可能起重要作用.

  10. Transgenic Eimeria mitis Expressing Chicken IL-4 Mediated Decrease in Pathogenicity Compared to Wild Type Eimeria mitis Strains in Broiler Chickens

    Directory of Open Access Journals (Sweden)

    Jamal Muhammad Khan1,2, Saeed El-Ashram, Hong Bin Liu3, Sher Hayat Khan4, Adnan Ayan5, Xian Yong Liu1,2, Hui Wang2, Xin Ming Tang1,2, Xun Suo1,2* and Mohammad Farooque Hassan4,6

    2016-11-01

    Full Text Available The present study was designed to establish transgenic Eimeria mitis (tE. mitis expressing chicken interleukin-4 (ChIL-4 and further exploitation of tE. mitis as a novel vaccine vector to control coccidiosis. For this purpose we compared the clinico-hematological alterations induced by wild type and tE. mitis carrying ChIL-4 in broilers birds. Wild type E. mitis (wE. mitis oocysts were nucleofected with double cassette vector and transgenic oocysts were propagated for stable transfection. Stability of the transfected E. mitis was observed by fluorescent microscopy and PCR analysis revealed the appearance of 411bp band suggestive of presence of IL-4 into the genome of tE. mitis. Birds inoculated with transgenic EmiChIL-4 excreted fewer oocysts and fecundity potential of tE. mitis turned out to be significantly lower than that of the wild type parent strain. Moderate clinical and behavioral signs such as restlessness, diarrhea, emaciation, decreased feed intake and loss of body weight was observed in birds inoculated with wE. mitis oocysts. The erythrocyte counts, Hb conc, PCV and MCHC decreased in birds infected with wE. mitis as compared to those infected with tE. mitis. The total leukocyte count including heterophils, eosinophil and basophils increased while lymphocytes were decreased in birds inoculated with wE. mitis as compared to birds in control group and those infected with tE.mitis. It was concluded that tE. mitis incorporated with ChIL-4 functions well as an adjuvant, conferring reduced fertility and compromised pathogenicity of tE. mitis. This discrimination, may be applied as a potential vaccine vector to control coccidiosis as well as pathogens from which antigens are expressed by tE. mitis.

  11. Research on change of levels of IL-10, IL-4 and total IgE in asthmatic children%哮喘患儿血清IL-10、IL-4与IgE水平的检测及意义

    Institute of Scientific and Technical Information of China (English)

    原树云

    2009-01-01

    目的:研究哮喘患儿白细胞介素10(IL-10)、白细胞介素4(IL-4)与免疫球蛋白E(IgE)水平的变化.方法:采用酶联免疫(ELISA)法测定不同时期支气管哮喘患儿血清IL-10、IL-4和IgE水平,并与正常对照组进行统计分析.结果:哮喘急性发作组血清IL-10水平显著低十缓解组和对照组(P<0.05),而IL-4和IgE水平却显著高于缓解期和对照组(P<0.05).IL-10与IgE呈负相关(r=-0.536,P<0.05).而IL-4与IgE呈正相关(r=0.548,P<0.05).结论:IL-10和IL-4参与支气管哮喘发病的整个过程,IL-10降低和IL-4升高是哮喘发病的重要因素;在支气管哮喘患儿不同时期检测血清IL-10和IL-4水平具有重要的临床意义.

  12. The association of sputum TSLP, IL-4, IL-5, IL-13 and serum IgE in patients with asthma%哮喘患者痰液TSLP、IL-4、IL-5、IL-13及血清IgE水平的相关性研究

    Institute of Scientific and Technical Information of China (English)

    李克明; 唐汉庆; 窦锡彬; 李晓华; 朱晓莹; 郑建宇

    2014-01-01

    目的 观察哮喘患者痰液胸腺基质淋巴细胞生成素(TSLP)、白细胞介素(IL)-4、IL-5、IL-13及血清免疫球蛋白E(IgE)水平并研究其相关性.方法 30例哮喘病例作为实验组,选取30例健康成年人作为对照组.取实验组和对照组外周静脉血,ELISA 法检测血清IgE水平;取哮喘患者痰液作为标本,ELISA 法检测TSLP、IL-4、IL-5、IL-13水平.和对照组比较,观察哮喘患者痰液TSLP、IL-4、IL-5、IL-13及血清IgE水平的变化并分析TSLP与IL-4、IL-5、IL-13及血清IgE水平的相关性.结果 和对照组比较,实验组TSLP、IL-4及 IgE水平均显著升高,差异有统计学意义(P<0.01).和对照组比较,实验组IL-5及IL-13水平升高,差异也有统计学意义(P<0.05).实验组TSLP与IL-4、IL-5、IL-13及血清IgE水平均存在正相关(r值分别为0.742,0.351,0.424,0.679,P均<0.01);IL-4与IgE存在正相关( r值为0.548,P<0.01 ).结论 哮喘患者的TSLP、IL-4、IL-5、IL-13及IgE水平均升高,是哮喘炎症的重要表现,哮喘患者TSLP水平与IL-4、IL-5、IL-13及IgE水平呈正相关,推测是TSLP发挥调控作用的节点之一.

  13. The expressions of serum IL-2, IL-4, IL-13 and IgE levels in patients with bronchial asthma%支气管哮喘患者外周血中IL-2IL-4IL-13和IgE的表达

    Institute of Scientific and Technical Information of China (English)

    胡林贵; 朱纪楼

    2011-01-01

    目的:探讨哮喘患者外周血中IL-2、IL-4、IL-13和IgE的水平变化及临床意义.方法:抽取哮喘患者及正常对照组空腹静脉血2ml,采用双抗体夹心法(ELISA法)检测血清中IL-2、IL-4、IL-13和IgE的含量.结果:急性发作组和缓解组中IL-4、IL-13、IgE的含量明显高于正常对照组,差异有统计学意义(P<0.01),IL-2的含量低于正常对照组,差异具有统计学意义.急性发作组IL-4、IL-13、IgE高于缓解组,IL-2的含量低于缓解组,差异均具有统计学意义(P<0.001).结论:支气管哮喘患者外周血中IL-2、IL-4、IL-13和IgE水平的变化与支气管哮喘发病进程及临床诊治具有密切联系.

  14. EFFECT OF INHALED GLUCOCOTICOIDS ON THE LEVELS OF IL-12, IL-4 AND IL-13 IN BRONCHIALASTHAMTIC CHILDREN%糖皮质激素对哮喘患儿血清中IL-12 IL-4和IL-13的影响

    Institute of Scientific and Technical Information of China (English)

    张婵; 吕继忠; 赵燕平

    2010-01-01

    目的 探讨糖皮质激素对哮喘患儿IL-12、IL-4 和IL-13的影响.方法 采用酶联免疫吸附的方法分别检测60 例哮喘急性发作期儿童(哮喘组)吸入丙酸倍氯米松2周前后血清中IL-12、IL-4 和IL-13水平,并与50例健康儿童(对照组)进行对照.结果 与对照组比较,哮喘组患儿治疗前IL-12 值明显下降,IL- 4、IL-13明显升高;与治疗前比较,治疗后IL-12水平明显升高、IL-4和IL-13水平明显下降(P<0.01).结论 吸入糖皮质激素能影响哮喘患儿血中IL-12、IL-4和IL-13的水平.

  15. Immunological parameters and gene polymorphisms (C-590T IL4, C-597A IL10 in severe bronchial asthma in children from the Krasnoyarsk region, West Siberia

    Directory of Open Access Journals (Sweden)

    Marina V. Smolnikova

    2013-08-01

    Full Text Available Background. Bronchial asthma is a common disease caused by interplay between multiple determinants, including genetic and immune variations. Objective. To investigate the main indices of humoral and cellular branches of immunity, features of cytokine regulation and cytokine genes in children with atopic bronchial asthma (BA with different levels of disease control. Design. Fifty children with controlled BA (CBA and 50 with uncontrolled BA (UBA were analyzed. Mean age in the sample was 13.36±2.24 years. A control group of healthy children (n=50 was also studied. All individuals were Russians (Eastern Slavs from the Krasnoyarsk Territory, West Siberia. Diagnoses, severity and level of disease control were defined according to the Global Initiative for Asthma (GINA recommendations. The lymphocytes were counted in blood using fluorescent microscopy. Humoral branch indices and cytokine levels (IL-2, IL-4, IL-10 and TNF-α in blood serum were measured by ELISA. Genotyping of single-nucleotide polymorphism (SNP in −590 position of the IL4 and −597 position of the IL10 gene was performed by restriction fragment length analysis. Results. No statistically significant differences in total IgE and cytokines blood levels were found in CBA and UBA. However, significant differences between the groups were found for CD3+, CD4+, and CD8+, cell counts. The T-590 allele of the IL4 gene, which is responsible for an increased serum level of IL-4, showed a tendency to an association with UBA. A decreased level of IL-10 enhances control over BA, which proves its association with the allelic variant A-597 IL10. Conclusions. Our data show that children with UBA have higher counts of CD3+, cells and an increase of sub-population of CD4+, -cells as well as higher levels of IgE, IL-4 and TNF-α in blood serum as compared to CBA. Polymorphisms of the IL4 and IL10 genes are associated with allergic inflammation in UBA.

  16. 哮喘患儿血清中sIL-2R,IL-2,IL-4,IL-13的测定与临床意义

    Institute of Scientific and Technical Information of China (English)

    张国祥; 许文龙

    2007-01-01

    目的 探讨哮喘患儿血清中sIL-2R,IL-2,IL-4,IL-13的水平变化及其与哮喘发病机制的关系.方法 每例患儿及正常对照组均取空腹静脉血并即时分离血清1 ml,用ELISA法检测血清中sIL-2R,IL-2,IL-4,IL-13的水平,并对检测结果 进行医学统计学分析处理.结果 哮喘急性发作组、哮喘缓解组的患儿血清中sIL-2R,IL-2,IL-4,IL-13的测定结果与正常对照组相比较经统计学分析均存在极其显著的差异(P<0.05).其中患儿哮喘急性发作组、哮喘缓解组血清中sIL-2R,IL-4,IL-13的测定结果 要明显高于正常对照组,而IL-2则明显低于正常对照组.此外,哮喘急性发作组与哮喘缓解组血清中IL-2,IL-4,IL-13的测定结果 相比较经统计学分析均存在显著的差异(P<0.05),而sIL-2R则无显著差异.结论 哮喘患儿血清中sIL-2R,IL-2,IL-4,IL-13的水平均存在显著的变化,说明它们在哮喘的发病机制中起着重要的作用.

  17. Association of IL-4RA single nucleotide polymorphisms, HLA-DR and HLA-DQ in children with Alternaria-sensitive moderate-severe asthma.

    Science.gov (United States)

    Knutsen, Alan P; Vijay, Hari M; Kariuki, Barbara; Santiago, Luis A; Graff, Ralph; Wofford, Jonathan D; Shah, Maulik R

    2010-03-18

    Asthma afflicts 6% to 8% of the United States population, and severe asthma represents approximately 10% of asthmatic patients. Several epidemiologic studies in the United States and Europe have linked Alternaria sensitivity to both persistence and severity of asthma. In order to begin to understand genetic risk factors underlying Alternaria sensitivity and asthma, in these studies we examined T cell responses to Alternaria antigens, HLA Class II restriction and HLA-DQ protection in children with severe asthma. Sixty children with Alternaria-sensitive moderate-severe asthma were compared to 49 children with Alternaria-sensitive mild asthma. We examined HLA-DR and HLA-DQ frequencies in Alternaria-sensitive asthmatic by HLA typing. To determine ratios of Th1/Th2 Alternaria-specific T-cells, cultures were stimulated in media alone, Alternaria alternata extract and Alt a1. Sensitivity to IL-4 stimulation was measured by up-regulation of CD23 on B cells. Children with Alternaria-sensitive moderate-severe asthma trended to have increased sensitivities to Cladosporium (46% versus 35%), to Aspergillus (43% versus 28%), and significantly increased sensitivities to trees (78% versus 57%) and to weeds (68% versus 48%). The IL-4RA ile75val polymorphism was significantly increased in Alternaria-sensitive moderate-severe asthmatics, 83% (0.627 allele frequency) compared to Alternaria-sensitive mild asthmatics, 57% (0.388 allele frequency). This was associated with increased sensitivity to IL-4 stimulation measured by significantly increased IL-4 stimulated CD23 expression on CD19+ and CD86+CD19+ B cells of Alternaria-sensitive moderate-severe asthmatics. IL-5 and IL-13 synthesis was significantly increased in Alternaria-sensitive moderate-severe asthmatics compared to mild asthmatics to Alternaria extract and Alt a1 stimulation. The frequency of HLA-DQB1*03 allele was significantly decreased in Alternaria-sensitive moderate-severe asthmatics compared to mild asthmatics, 39

  18. Association of IL-4RA single nucleotide polymorphisms, HLA-DR and HLA-DQ in children with Alternaria-sensitive moderate-severe asthma

    Directory of Open Access Journals (Sweden)

    Santiago Luis A

    2010-03-01

    Full Text Available Abstract Background Asthma afflicts 6% to 8% of the United States population, and severe asthma represents approximately 10% of asthmatic patients. Several epidemiologic studies in the United States and Europe have linked Alternaria sensitivity to both persistence and severity of asthma. In order to begin to understand genetic risk factors underlying Alternaria sensitivity and asthma, in these studies we examined T cell responses to Alternaria antigens, HLA Class II restriction and HLA-DQ protection in children with severe asthma. Methods Sixty children with Alternaria-sensitive moderate-severe asthma were compared to 49 children with Alternaria-sensitive mild asthma. We examined HLA-DR and HLA-DQ frequencies in Alternaria-sensitive asthmatic by HLA typing. To determine ratios of Th1/Th2 Alternaria-specific T-cells, cultures were stimulated in media alone, Alternaria alternata extract and Alt a1. Sensitivity to IL-4 stimulation was measured by up-regulation of CD23 on B cells. Results Children with Alternaria-sensitive moderate-severe asthma trended to have increased sensitivities to Cladosporium (46% versus 35%, to Aspergillus (43% versus 28%, and significantly increased sensitivities to trees (78% versus 57% and to weeds (68% versus 48%. The IL-4RA ile75val polymorphism was significantly increased in Alternaria-sensitive moderate-severe asthmatics, 83% (0.627 allele frequency compared to Alternaria-sensitive mild asthmatics, 57% (0.388 allele frequency. This was associated with increased sensitivity to IL-4 stimulation measured by significantly increased IL-4 stimulated CD23 expression on CD19+ and CD86+CD19+ B cells of Alternaria-sensitive moderate-severe asthmatics. IL-5 and IL-13 synthesis was significantly increased in Alternaria-sensitive moderate-severe asthmatics compared to mild asthmatics to Alternaria extract and Alt a1 stimulation. The frequency of HLA-DQB1*03 allele was significantly decreased in Alternaria-sensitive moderate

  19. Angiogenesis related genes NOS3, CD14, MMP3 and IL4R are associated to VEGF gene expression and circulating levels in healthy adults.

    Science.gov (United States)

    Saleh, Abdelsalam; Stathopoulou, Maria G; Dadé, Sébastien; Ndiaye, Ndeye Coumba; Azimi-Nezhad, Mohsen; Murray, Helena; Masson, Christine; Lamont, John; Fitzgerald, Peter; Visvikis-Siest, Sophie

    2015-10-05

    Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis. The aim was to assess the genetic connections between the angiogenesis-related NOS3, CD14, MMP3, IL4R, IL4 genes and VEGF expression and plasma levels. The associations between VEGF plasma levels with the polymorphisms of NOS3, CD14, MMP3, IL4R, and IL4 were assessed in 403 healthy unrelated adults. The epistatic and environmental interactions were explored, including four VEGF-related polymorphisms previously identified. The VEGF expression in peripheral blood mononuclear cells was quantified (n = 65) for the VEGF121, VEGF145, VEGF165, and VEGF189 isoforms. The polymorphism rs1799983 of NOS3 was associated with the sum of all VEGF isoforms mRNA levels (P = 0.032) and VEGF145 (P = 0.033). Rs1800779 of NOS3 interacted with rs3918226 of the same gene and with the rs2569190 of CD14 (P = 0.022, P = 0.042, respectively) for VEGF plasma levels. Other epistatic interactions included the rs1801275 of IL4R with the rs6921438 (VEGF-related variant) and rs3025058 of MMP3 (P = 0.042, P = 0.010 respectively) and the rs2569190 of CD14 with the rs3025058 of MMP3 (P = 0.0119). We also identified an interaction of rs1800779 with obesity, high-density lipoprotein cholesterol and triglycerides (P = 0.018, P = 0.005, P = 0.043, respectively) as well as the interaction of rs6921438 with hypertension (P = 0.028). Our findings indicated that genetic variants of NOS3, CD14, MMP3 and IL4R are implicated in the determination of VEGF expression and plasma levels. Thus, they support the hypothesis that in physiological conditions there are complex biological relationships between pathways (such as angiogenesis and inflammation), which are involved in the development of chronic diseases.

  20. Interleukin 4 receptor on human lung cancer: a molecular target for cytotoxin therapy.

    Science.gov (United States)

    Kawakami, Mariko; Kawakami, Koji; Stepensky, Vitaly A; Maki, Richard A; Robin, Howard; Muller, Wayne; Husain, Syed R; Puri, Raj K

    2002-11-01

    Previous studies have demonstrated that human lung tumor cell lines express interleukin 4 (IL-4) receptors, and IL-4 can mediate modest to moderate antiproliferative activity in vitro and in vivo in animal models of human lung tumors. On the basis of these studies, IL-4 was tested in clinical trials; however, it showed little antitumor activity in lung cancer patients. In the present study, we examined the expression of IL-4 receptors (IL-4Rs) in lung tumor samples and normal lung tissues and tested whether an IL-4R targeted agent will have better antitumor activity in vitro and in vivo compared with IL-4. IL-4R expression was tested by immunohistochemistry in 54 lung tumor samples and normal lung tissues in a tissue array, by reverse-transcription PCR and Northern blot analyses in lung tumor cell lines. Cytotoxic activity of IL-4 cytotoxin [IL-4(38-37)-PE38KDEL], composed of a circular permuted IL-4 and a mutated form of Pseudomonas exotoxin (PE38KDEL) was tested by protein synthesis inhibition and clonogenic assays in seven lung tumor cell lines. Antitumor activity of IL-4 cytotoxin was tested in vitro and in immunodeficient animal models of human lung tumors. We observed that IL-4Rs are expressed at higher levels in situ in lung tumor samples compared with normal lung tissues and IL-4 cytotoxin is highly and specifically cytotoxic to lung tumor cell lines in vitro. Intratumoral and i.p. administration of IL-4 cytotoxin to immunodeficient mice with s.c. established human lung H358 non-small cell lung cancer tumors mediated considerable antitumor activity in a dose-dependent manner with the higher dose producing durable complete responses. On the other hand, H460 non-small cell lung cancer tumors expressing low levels of IL-4R did not respond to IL-4 cytotoxin therapy. Because IL-4 cytotoxin mediates its antitumor activity through IL-4R, and a variety of lung tumors expressed high levels of IL-4R, we propose testing the safety of this agent in patients with lung

  1. Integration of Multiple Genomic and Phenotype Data to Infer Novel miRNA-Disease Associations.

    Science.gov (United States)

    Shi, Hongbo; Zhang, Guangde; Zhou, Meng; Cheng, Liang; Yang, Haixiu; Wang, Jing; Sun, Jie; Wang, Zhenzhen

    2016-01-01

    MicroRNAs (miRNAs) play an important role in the development and progression of human diseases. The identification of disease-associated miRNAs will be helpful for understanding the molecular mechanisms of diseases at the post-transcriptional level. Based on different types of genomic data sources, computational methods for miRNA-disease association prediction have been proposed. However, individual source of genomic data tends to be incomplete and noisy; therefore, the integration of various types of genomic data for inferring reliable miRNA-disease associations is urgently needed. In this study, we present a computational framework, CHNmiRD, for identifying miRNA-disease associations by integrating multiple genomic and phenotype data, including protein-protein interaction data, gene ontology data, experimentally verified miRNA-target relationships, disease phenotype information and known miRNA-disease connections. The performance of CHNmiRD was evaluated by experimentally verified miRNA-disease associations, which achieved an area under the ROC curve (AUC) of 0.834 for 5-fold cross-validation. In particular, CHNmiRD displayed excellent performance for diseases without any known related miRNAs. The results of case studies for three human diseases (glioblastoma, myocardial infarction and type 1 diabetes) showed that all of the top 10 ranked miRNAs having no known associations with these three diseases in existing miRNA-disease databases were directly or indirectly confirmed by our latest literature mining. All these results demonstrated the reliability and efficiency of CHNmiRD, and it is anticipated that CHNmiRD will serve as a powerful bioinformatics method for mining novel disease-related miRNAs and providing a new perspective into molecular mechanisms underlying human diseases at the post-transcriptional level. CHNmiRD is freely available at http://www.bio-bigdata.com/CHNmiRD.

  2. Expression and Clinical Value of IL-4 and IL-13 in Patients、with Allergic Rhinitis%尘螨变应性鼻炎全血细胞IL-4、IL-13的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    陈靖; 陈冬; 李添应; 林志斌; 冯炼强

    2008-01-01

    目的 探讨IL-4、IL-13在变应性鼻炎发病机制中的作用及IL-4、IL-13拮抗剂治疗变应性鼻炎的临床意义.方法 取52例变应性鼻炎(实验组)及25例无过敏性疾病(对照组)患者的外周血,用PMA(phorbol 12-myristate 13-acetate佛波酯)+inomycin(离子霉素)及标准化尘螨抗原刺激后经细胞内染色,流式细胞仪检测IL-4、IL-13、IFN-γ的表达细胞百分数,ELISA检测血清IL-4、IL-13含量.结果对照组经标准化尘螨变应原刺激后细胞内测出IFN-γ为0.3%~0.4%,但检测不到IL-4与IL-13,经PMA+inomycin刺激后IFN-γ为5.0%~12.4%、IL-4为0.5%~0.8%、IL-13为0%~0.2%;实验组经标准化尘螨变应原刺激后IFN-γ为0.3%~0.5%、IL-4为0.9%~1.3%、IL-13为0.5%~0.9%,经PMA+inomycin刺激后IFN-γ为17.3%~24.0%、IL-4为2.1%~3.5%、IL-13为0.8%~2.0%.实验组血清中IL-4含量为(1.768±0.485)pg/ml、IL-13为(5.427±1.263)pg/ml,对照组IL-4与IL-13含量均低于敏感度.结论 IL-4、IL-13在变应性鼻炎患者中表达升高,参与了变态反应过程,为临床应用IL-4,IL-13拮抗剂治疗变应性鼻炎提供了依据.

  3. IL-4及IL-9在D-IBS患者外周血中的表达及其与肠道MC活化的关系

    Institute of Scientific and Technical Information of China (English)

    沈敏瑾

    2016-01-01

    Objective To investigate the level of serum IL-4 and IL-9 in D-IBS patients as well as the number of MC in colon. Methods 30 D-IBS patients according to Rome III diagnostic criteria were enrolled in the study,and 30 healthy individuals as a normal control. Toluidine blue staining was used to determine the number of mast cells(MCs). Expression of IL-4 and IL-9 in serum were measured by enzyme-linked immunosorbent assay(ELISA). Results The number of colonic MC in D-IBS group was more than that in control group(4.43±0.21vs2.12±0.27) (P<0.05). Expression of serum IL-4 and IL-9 in D-IBS group were higher than that in control group(42.76±5.71 vs21.19±6.17,30.43±7.45 vs26.74±5.12)(P<0.05).Conclusions The hypothesis was supported that the increased expression of serum IL-4 and IL-9 may lead to mast cells degranulation,which resulting in the clinical symptoms of D-IBS.%目的:通过入组腹泻性肠易激综合征(D-IBS)患者,观察外周血中IL-4及IL-9的表达及肠道肥大细胞(MC)活化情况。方法依据罗马III诊断标准入选D-IBS患者30例,健康对照组30例,采用甲苯胺蓝染色法计数回盲部结肠黏膜MC,ELISA法检测血清中IL-4、IL-9表达。结果与正常对照组比较,IBS患者MC数量增多(4.43±0.21 vs 2.12±0.27)(P<0.05),黏膜IL-4及血清IL-9的表达均高于对照组(42.76±5.71 vs 21.19±6.17,30.43±7.45 vs 26.74±5.12)(P<0.05)。结论 D-IBS患者血清中存在IL-4、IL-9的表达升高,其可能通过促进MC活化脱颗粒,从而引起IBS临床症状。

  4. Global Identification of Disease Associated Genes in Fragile X Cells

    Science.gov (United States)

    2016-08-01

    AWARD NUMBER: W81XWH-15-1-0204 TITLE: Global Identification of Disease-Associated Genes in Fragile X Cells PRINCIPAL INVESTIGATOR: Wenyi Feng...Global Identification of Disease-Associated Genes in Fragile X Cells 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0204 GRANT1171 2389... genes in fragile X cells compared to normal cells. o What was accomplished under these goals? Below I list the experiments and conclusions for each goal

  5. Increased production of IL-4 and IL-12p40 from bronchoalveolar lavage cells are biomarkers of Mycobacterium tuberculosis in the sputum.

    Directory of Open Access Journals (Sweden)

    Anna Nolan

    Full Text Available BACKGROUND: Tuberculosis (TB causes 1.45 million deaths annually world wide, the majority of which occur in the developing world. Active TB disease represents immune failure to control latent infection from airborne spread. Acid-fast bacillus (AFB seen on sputum smear is a biomarker for contagiousness. METHODS: We enrolled 73 tuberculosis patients with extensive infiltrates into a research study using bronchoalveolar lavage (BAL to sample lung immune cells and assay BAL cell cytokine production. All patients had sputum culture demonstrating Mycobacterium tuberculosis and 59/73 (81% had AFB identified by microscopy of the sputum. Compared with smear negative patients, smear positive patients at presentation had a higher proportion with smoking history, a higher proportion with temperature >38.5(0 C, higher BAL cells/ml, lower percent lymphocytes in BAL, higher IL-4 and IL-12p40 in BAL cell supernatants. There was no correlation between AFB smear and other BAL or serum cytokines. Increasing IL-4 was associated with BAL PMN and negatively associated with BAL lymphocytes. Each 10-fold increase in BAL IL-4 and IL-12p40 increased the odds of AFB smear positivity by 7.4 and 2.2-fold, respectively, in a multi-variable logistic model. CONCLUSION: Increasing IL-4 and IL-12p40 production by BAL cells are biomarkers for AFB in sputum of patients who present with radiographically advanced TB. They likely reflect less effective immune control of pathways for controlling TB, leading to patients with increased infectiousness.

  6. Intracellular IL-4, IL-5, and IFN-γ as the main characteristic of CD4+CD30+ T cells after allergen stimulation in patients with vernal keratoconjunctivitis

    Science.gov (United States)

    Magaña, Diana; Aguilar, Gustavo; Linares, Marisela; Ayala-Balboa, Julio; Santacruz, Concepción; Chávez, Raúl; Estrada-Parra, Sergio; Garfias, Yonathan; Lascurain, Ricardo; Jiménez-Martínez, Maria C.

    2015-01-01

    Background Vernal keratoconjunctivitis (VKC) is a severe form of allergic conjunctivitis, in which inflammatory infiltrates of the conjunctiva are characterized by CD3+ and CD30+ cells. Until today, the functional involvement of CD30+ T cells in VKC was unclear. Our aim was to evaluate the functional characteristics of CD30+ T cells after allergen stimulation in peripheral blood mononuclear cells obtained from patients with VKC. Methods Seventeen consecutive patients at the Institute of Ophthalmology with active forms of VKC were included. Results After allergen stimulation, we observed the frequency of CD30+ T cells increased compared with non-stimulated cells (p<0.0001). The CD30+ T cells responded to the specific allergen-inducing expression of intracellular interleukin-4 (IL-4), IL-5, and interferon-gamma (IFN-γ) compared with the CD30- T cells (p<0.0001). Increased early secretion of soluble CD30 was observed in the supernatant of the cultured cells from patients with keratoconjunctivitis, compared with healthy controls (p=0.03). Blockage with IL-4 significantly diminished CD30 frequency in the allergen-stimulated cells. Conclusions Our results suggest that after allergenic stimulation, CD4+CD30+ cells are the most important source of IL-4, IL-5, and IFN-γ. IL-4 acts as an activation loop that increases CD30 expression on T cells after specific stimulation. These findings suggest that CD4+CD30+ T cells are effector cells and play a significant role in the immune pathogenic response in patients with vernal keratoconjunctivitis. PMID:25999672

  7. Increased midgestational IFN-γ, IL-4 and IL-5 in women bearing a child with autism: A case-control study

    Directory of Open Access Journals (Sweden)

    Goines Paula E

    2011-08-01

    Full Text Available Abstract Background Immune anomalies have been documented in individuals with autism spectrum disorders (ASDs and their family members. It is unknown whether the maternal immune profile during pregnancy is associated with the risk of bearing a child with ASD or other neurodevelopmental disorders. Methods Using Luminex technology, levels of 17 cytokines and chemokines were measured in banked serum collected from women at 15 to 19 weeks of gestation who gave birth to a child ultimately diagnosed with (1 ASD (n = 84, (2 a developmental delay (DD but not autism (n = 49 or (3 no known developmental disability (general population (GP; n = 159. ASD and DD risk associated with maternal cytokine and chemokine levels was estimated by using multivariable logistic regression analysis. Results Elevated concentrations of IFN-γ, IL-4 and IL-5 in midgestation maternal serum were significantly associated with a 50% increased risk of ASD, regardless of ASD onset type and the presence of intellectual disability. By contrast, elevated concentrations of IL-2, IL-4 and IL-6 were significantly associated with an increased risk of DD without autism. Conclusion The profile of elevated serum IFN-γ, IL-4 and IL-5 was more common in women who gave birth to a child subsequently diagnosed with ASD. An alternative profile of increased IL-2, IL-4 and IL-6 was more common for women who gave birth to a child subsequently diagnosed with DD without autism. Further investigation is needed to characterize the relationship between these divergent maternal immunological phenotypes and to evaluate their effect on neurodevelopment.

  8. The prokineticin receptor agonist Bv8 decreases IL-10 and IL-4 production in mice splenocytes by activating prokineticin receptor-1

    Directory of Open Access Journals (Sweden)

    Negri Lucia

    2008-10-01

    Full Text Available Abstract Background Bv8, prokineticin-1, or endocrine gland-vascular endothelial growth factor, and prokineticin-2 are recently isolated peptide agonists of two G protein-coupled receptors, prokineticin receptor-1 (PROKR 1 and PROKR 2, and have been described as affecting a number of myeloid cell functions. We evaluated the impact of Bv8 on lymphoid cells by investigating its ability to modulate T cell cytokine balance in mouse. Results The production of T-helper1 cytokines (IL-2, IFN-γ and IL-1β, the T-helper 2 cytokine IL-4, and the anti-inflammatory cytokine IL-10 by mouse splenocytes was evaluated after polyclonal stimulation or immunisation with the keyhole limpet hemocyanin protein antigen by measuring cytokine levels. When added in vitro to Con-A-stimulated splenocytes, Bv8 significantly increased IL-1β and decreased IL-4 and IL-10; IL-2 and IFN-γ were not affected. Similar results were obtained when Bv8 was administered in vivo. In KLH-immunised mice, splenocytes restimulated in vitro with KLH and Bv8 produced significantly smaller amounts of IL-4 and IL-10. KLH-induced IL-10 and IL-4 production was also significantly blunted in animals administered Bv8 in vivo at the time of KLH immunisation or two weeks later. The Bv8-induced effects were lost in mice lacking the PROKR 1 gene, thus indicating that PROKR 1 is the receptor involved in the modulation of cytokines. Conclusion These findings indicate that Bv8/prokineticin-1 is a novel modulator of lymphoid functions, and may be a suitable target for new immunopharmacological strategies.

  9. IL-4 and IL-13 alter plasmacytoid dendritic cell responsiveness to CpG DNA and herpes simplex virus-1

    NARCIS (Netherlands)

    Tel, J.; Torensma, R.; Figdor, C.G.; Vries, I.J.M. de

    2011-01-01

    Human plasmacytoid dendritic cells (pDCs) are found in skin lesions in a wide variety of diseases. The role of the microenvironment in these lesions on the function of human pDCs remains elusive. We sought to determine the effect of T(h)2 cytokines on the ability of human pDCs to respond to CpG

  10. 哮喘患者血清中IL-4、IL-12、IL-13、IFN-γ、IgE水平的测定及其临床意义%Changes of Serum IL-4,IL-12,IL-13,IFN-y and IgE Levels and Their Clinical Significance in Acute Attack of Asthma

    Institute of Scientific and Technical Information of China (English)

    高毅云; 王冬梅; 刘传桂

    2014-01-01

    目的:研究哮喘患者血清中白细胞介素-4、白细胞介素-12、白细胞介素-13、γ干扰素、免疫球蛋白E水平的测定及临床意义。方法:采用生物素亲合素双抗体夹心酶联和间接酶联免疫吸附法测定98例哮喘患者不同分期和分级血清IL-4、IL-12、IL-13以及IFN-γ水平和IgE水平,观察不同分期和分级各项观察指标的水平,并与60例健康对照组进行比较。结果:观察组及发作期患者IL-4、IL-13、IgE水平均明显升高(P<0.05),IFN-γ、IL-12水平均明显降低(P<0.05)。结论:IL-4、IL-12、IL-13、IFN-γ、IgE在哮喘发病中起重要调控作用。%Objective:To investigate the changes of serum IL-4,IL-12,IL-13,IFN-γand IgE Levels and their clinical significance in acute attack of asthma.Method:Serum levels of IL-4,IL-12,IL-13,IFN-γand IgE of 98 asthma patients in different periodizations and different classifications and its catabasis respectively were determined through double-antibody sandwich and indirect ELISA.Levels of IL-4,IL-12,IL-13,IFN-γand IgE were compared between the observation group and the healthy control group(60 cases).Result:The levels of IL-4,IL-13,IgE of the observation group and acute attack stage increased significantly(P<0.05).The levels of IFN-γ,IL-12 of the observation group and acute attack stage reduced significantly(P<0.05).Conclusion:IL-4,IL-12,IL-13,IFN-γand IgE play crucial roles in the pathogenesis of asthma.

  11. 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.

  12. IL-4, IL-10 and high sensitivity-CRP as potential serum biomarkers of persistent/recurrent disease in papillary thyroid carcinoma with/without Hashimoto's thyroiditis.

    Science.gov (United States)

    Stanciu, Adina E; Serdarevic, Nafija; Hurduc, Anca E; Stanciu, Marcel M

    2015-11-01

    To investigate the potential role of interleukin 4 (IL-4), interleukin 10 (IL-10) and high-sensitivity C-reactive protein (hs-CRP) as serum biomarkers of persistent/recurrent disease in papillary thyroid carcinoma (PTC) with/without Hashimoto's thyroiditis (HT). Eighty consecutive patients (64 F/16 M, 43.2 ± 12.7 years) with PTC and 40 (37 F/3 M, 40.6 ± 12.3 years) with papillary thyroid carcinoma associated with Hashimoto's thyroiditis (PTC + HT) were evaluated before radioiodine therapy. A control group of 20 patients with HT without thyroid cancer (18 F/2 M, 47.3 ± 2.8 years) was included in the study for the comparison of cytokine levels. No meaningful differences were found in clinical outcomes between PTC and PTC + HT groups (47.5% vs. 45% persistent/recurrent disease). Serum IL-4, IL-10 and hs-CRP levels were higher in patients with persistent/recurrent disease compared to those without recurrence (p disease than in patients with HT or PTC (with or without recurrence) (p disease. Increased levels of serum IL-4, IL-10 and hs-CRP are associated with persistent/recurrent disease in PTC and PTC + HT patients. Our results suggest that these biomarkers might be used to improve patient stratification according to the risk of recurrence, especially in patients with PTC + HT, where Tg levels are not reliable due to presence of TgAb.

  13. Chelidonine, a principal isoquinoline alkaloid of Chelidonium majus, attenuates eosinophilic airway inflammation by suppressing IL-4 and eotaxin-2 expression in asthmatic mice.

    Science.gov (United States)

    Kim, Seung-Hyung; Hong, Jung-Hee; Lee, Young-Cheol

    2015-12-01

    Chelidonine, a major bioactive, isoquinoline alkaloid ingredient in Chelidonium majus, exhibits anti-inflammatory and other pharmacological properties. However, its molecular mechanisms in asthma remain unclear. In this work we investigated chelidonine's effect and mechanism in airway inflammation in a mouse model of allergic asthma. The mice were sensitized to ovalbumin followed by aerosol allergen challenges and determination of chelidonine's effect on enhanced pause (Penh), pulmonary eosinophilic infiltration, eotaxin-2, interleukin-4 (IL-4), IL-13, OVA-specific IgE production, and several transcription factors. Chelidonine strongly suppressed airway eosinophilia, expression of eotaxin-2, IL-4, and IL-13 cytokine production in bronchoalveolar lavage fluid (BALF). It also attenuated lung IL-17, and eotaxin-2 mRNA expression levels. Moreover, it suppressed eotaxin-2 and IL-17 production in accordance with up- and downregulation of forkhead box p3 (Foxp3), and signal transducer and activator of transcription (STAT6) expression, respectively. Chelidonine has profound inhibitory effects on airway inflammation and this effect is caused by suppression of IL-4, eotaxin-2, and OVA-specific IgE production through the STAT6 and Foxp3 pathways. So chelidonine can improve allergic asthma in mice and be a novel anti-asthma therapeutic. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  14. The cytokines (IFN-gamma, IL-2, IL-4, IL-10, IL-17) and Treg cytokine (TGF-beta1) levels in adults with immune thrombocytopenia.

    Science.gov (United States)

    Ma, Liangliang; Liang, Yan; Fang, Meiyun; Guan, Yanchun; Si, Yang; Jiang, Feng; Wang, Fangting

    2014-09-01

    Previous studies have indicated that autoimmune diseases might be caused by an imbalance of T helper cells (Th), cytokines, and regulatory T cells (Treg) cytokines. We measured the plasma concentrations of Th1-associated cytokines (IFN-gamma, IL-2), Th2 -associated cytokines (IL-4, IL-10), Th17-associated cytokine (IL-17) and Treg -associated cytokine (TGF-beta1) in adult patients with immune thrombocytopenia (ITP) and evaluated their clinical relevance. Plasma IFN-gamma, IL-2, IL-4, IL-10, IL-17 and TGF-beta1 concentrations of 52 ITP patients and 30 age- and sex-matched healthy controls were measured by enzyme-linked immunosorbent assay method (ELISA). Concentration of Th2 cytokines (IL-4 and IL-10) were significantly higher in ITP patients compared to controls (P cytokines (IFN-gamma, IL-2), Th17 cytokine (IL-17) and Treg cytokine (TGF-beta1) were lower in ITP patients (P cytokine concentration among the other subgroups in ITP patients was found. Among the ITP patients, concentration of IFN-gamma correlated positively and significantly with PAIgG (r = 0.48, P = 0.02). A significant correlation was neither found between other cytokine levels and platelet count, nor between cytokine levels and megakaryocytes number, nor between cytokines levels and PAIgG or GPIIb/IIIa and/or GPIb/IX autoantibodies. The present study demonstrates that an imbalance of Th and Treg cytokines may mediate the pathogenesis of ITP.

  15. IL-4 protects the B-cell lymphoma cell line CH31 from anti-IgM-induced growth arrest and apoptosis:contribution of the PI-3' kinase/AKT pathway

    Institute of Scientific and Technical Information of China (English)

    Gregory B Carey; Elena Semenova; Xiulan Qi; Achsah D Keegan

    2007-01-01

    Interleukin-4(IL-4)promotes lymphocyte survival and protects primary lymphomas from apoptosis.Previous studies reported differential requirements for the signal transducer and activator of transcription 6(STAT6)and IRS2/phosphatidylinositol 3 kinase(PI-3K)signaling pathways in mediating the IL-4-induced protection from Fas-mediated apoptosis.In this study,we characterized IL-4-activated signals that suppress anti-IgM-mediated apoptosis and growth arrest of CH31,a model B-cell lymphoma line.In CH31,anti-IgM treatment leads to the loss of mitochondrial membrane potential,phospho-Akt,phospho-CDK2,and c-myc protein.These losses are followed by massive induction ofp27Kip1 protein expression,cell cycle arrest,and apoptosis.Strikingly,IL-4 treatment prevented or reversed these changes.Furthermore,IL-4 suppressed the activation of caspases 9 and 3,and,in contrast to previous reports,induced the phosphorylation(deactivation)of BAD.IL-4 treatment also induced expression of BclxL,a STAT6-dependent gene.Pharmacologic inhibitors and dominant inhibitory forms of PI-3K andAkt abrogated the anti-apoptotic function of IL-4.These results suggest that the IL-4 receptor activates several signaling pathways,with the Akt pathway playing a major role in suppression of the apoptotic program activated by anti-IgM.

  16. IFN -γ、IL -4在子痫前期患者血清中的表达水平及平衡变化%The expression levele of IFN - γ, IL -4, in pre - eclamptic serum and to ivestigate their role in pre - eclampisa

    Institute of Scientific and Technical Information of China (English)

    梁慧丽; 杨海澜; 索明莉

    2012-01-01

    Objective: To compare the expression levels of IFN - γ, EL - 4 and IFN - γ/IL - 4 in pre - eclamptic serum and to investigate their role in pre - eclampisa. Methods: In 15 normal pregnant women , 15 mild pre - eclampsia patients and 15 severe pre -eclampsia (SPE) patients, The expression levels of IFN -γ and IL-4 in the three groups were detected by ELISA. Results; ① The expression level of IFN - γ in the SPE group higher than normal pregnant and mild pre - eclampsia, and the difference is significant (P0.05). ②The expression level of IL - 4 in the SPE group decreased compared with the normal group, there was significantly statistical difference (P 0. 05). The was no difference between the mild pre -eclampsia and the normal group ( P > 0.05). ③The ratio of IFN - γ and IL - 4 in the SPE group higher than normal pregnant, and the difference is significant (P < 0.05 ). Conclusions; The disbalant and disorder expression levels of IFN -γ and IL - 4 may be one of the major links in the pathogenesis of immunology of severe pre - eclampsia. Imbalance of Th1/Th2 might lead to hypertensive disorder complicating pregnancy.%目的 通过观察子痫前期患者血清中IFN -γ、IL-4水平,来探讨Th1、Th2型细胞因子在子痫前期疾病发病中所起的作用.方法 用ELISA法分别测定正常孕妇15例、重度子痫前期患者15例、轻度子痫前期患者15例血清中IFN-γ、IL-4水平及计算IFN -γ/IL-4的比值.结果 ①血清中IFN -γ:轻度子痫前期组与正常妊娠组差异无统计学意义(P>0.05);重度子痫前期组明显高于正常妊娠组、轻度子痫前期组,差异有统计学意义(P<0.05).②血清中IL -4:轻度子痫前期组与正常妊娠组相比差异无统计学意义(P>0.05);重度子痫前期组与轻度子痫前期组相比差异无统计学意义(P>0.05);重度子痫前期组低于正常妊娠组,差异有统计学意义(P<0.05).③血清中IFN-γ/IL-4:轻度子痫前期组与正常妊娠组

  17. Large-scale prediction of microRNA-disease associations by combinatorial prioritization algorithm

    Science.gov (United States)

    Yu, Hua; Chen, Xiaojun; Lu, Lu

    2017-03-01

    Identification of the associations between microRNA molecules and human diseases from large-scale heterogeneous biological data is an important step for understanding the pathogenesis of diseases in microRNA level. However, experimental verification of microRNA-disease associations is expensive and time-consuming. To overcome the drawbacks of conventional experimental methods, we presented a combinatorial prioritization algorithm to predict the microRNA-disease associations. Importantly, our method can be used to predict microRNAs (diseases) associated with the diseases (microRNAs) without the known associated microRNAs (diseases). The predictive performance of our proposed approach was evaluated and verified by the internal cross-validations and external independent validations based on standard association datasets. The results demonstrate that our proposed method achieves the impressive performance for predicting the microRNA-disease association with the Area Under receiver operation characteristic Curve (AUC), 86.93%, which is indeed outperform the previous prediction methods. Particularly, we observed that the ensemble-based method by integrating the predictions of multiple algorithms can give more reliable and robust prediction than the single algorithm, with the AUC score improved to 92.26%. We applied our combinatorial prioritization algorithm to lung neoplasms and breast neoplasms, and revealed their top 30 microRNA candidates, which are in consistent with the published literatures and databases.

  18. Large-scale prediction of microRNA-disease associations by combinatorial prioritization algorithm

    Science.gov (United States)

    Yu, Hua; Chen, Xiaojun; Lu, Lu

    2017-01-01

    Identification of the associations between microRNA molecules and human diseases from large-scale heterogeneous biological data is an important step for understanding the pathogenesis of diseases in microRNA level. However, experimental verification of microRNA-disease associations is expensive and time-consuming. To overcome the drawbacks of conventional experimental methods, we presented a combinatorial prioritization algorithm to predict the microRNA-disease associations. Importantly, our method can be used to predict microRNAs (diseases) associated with the diseases (microRNAs) without the known associated microRNAs (diseases). The predictive performance of our proposed approach was evaluated and verified by the internal cross-validations and external independent validations based on standard association datasets. The results demonstrate that our proposed method achieves the impressive performance for predicting the microRNA-disease association with the Area Under receiver operation characteristic Curve (AUC), 86.93%, which is indeed outperform the previous prediction methods. Particularly, we observed that the ensemble-based method by integrating the predictions of multiple algorithms can give more reliable and robust prediction than the single algorithm, with the AUC score improved to 92.26%. We applied our combinatorial prioritization algorithm to lung neoplasms and breast neoplasms, and revealed their top 30 microRNA candidates, which are in consistent with the published literatures and databases. PMID:28317855

  19. [Gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha) and interleukins 2, 4 and 6 (IL-2, IL-4, IL-6) in cervical-uterine cells of intraepithelial neoplasia: a preliminary report].

    Science.gov (United States)

    Pardo-Govea, Tatiana; Callejas, Diana; Núñez-Troconis, José; Araujo, Mary; Costa, Luciana; Pons, Héctor; Delgado, Mariela; Monsalve, Francisca

    2005-03-01

    The purpose of this work was to determine the expression of type Th1 cytokines: IL-2 and IFNgamma, and Th2: IL-4 and IL-6, as well as TNF-alpha in patients with precancerous lesions of the uterine cervix and their relationship with the human papiloma virus (HPV). 30 patients with precancerous lesions (NIC 1: 70%, NIC 2: 16.7% and NIC 3: 1.3%) and 9 normal controls were studied. A clinical history, gynecological evaluation, cytology and an uterine biopsy were carried out in each patient and control. PCR was used for the diagnosis of HPV. IFN-gamma expression (positive cells/field) was increased in patients with NIC (5.06 +/- 4.7 vs 0 in the control group; p < 0.05). TNFa was a little higher in pathologycal tissues than in the controls (5.23 +/- 3.63 vs 1.55 +/- 2.65; p < 0.05). IL-2 was higher in pathologycal cases than in the controls (8.73 +/- 5.23 vs 0.33 +/- 1, p < 0.05). IL-4 were expressed in both, patients and controls (6.53 +/- 5.23 vs 5.77 +/- 7.32). IL-6 was also higher in patients (4.63 +/- 3.34 vs 0.77 +/- 2.33; p < 0.05). When the HPV status was considered, only IFN-gamma (p < 0.05) and IL-2 (p < 0.05) were significantly higher in HPV positive patients (n = 4) compared to controls. When HPV+ patients were compared with HPV- patients, only IFNgamma was significant (11.5 +/- 5 vs 4.07 +/- 3.8; p < 0.05). In conclusion, Type Th1 immune response prevails in patients with precancerous lesions, whether they are HPV positive or not.

  20. Levels of IL-4 and markers of M2 macrophages at early stage of Fasciola hepatica infection in mice%小鼠感染肝片吸虫早期IL-4/IFN-γ及M2巨噬细胞标记分子的变化

    Institute of Scientific and Technical Information of China (English)

    罗洪林; 张文韬; 郭智莉; 周雪梅; 周容琼; 周作勇

    2013-01-01

    To address the dominant type of cellular immune responses and levels of M2 macrophages markers at the early stage of Fasciola hepatica infection,the wild type female BALB/c mice were infected with F.hepatica metacercariae and the species-specific PCR was applied to identify the infection of F.hepatica at different time post infection.The indirect ELISA and real-time PCR were used to test the levels of IL-4/IFN-γ and mRNA levels of IL-4,GATA3,Relm α and Ym1 in pleural cavity at week 1,3,5 and 7 post infection,respectively.The results showed at each time point,the ITS2 sequence were successfully identified and the IL-4 was dominant with comparison to IFN-γ at week 1,3 and 5,but no difference at week 7.The mRNA levels of IL-4 and GATA3 were significantly higher than the controls with no difference between both during infection.Moreover,both were significantly increased at week 3 compared to the rest time points,respectively.The mRNA levels of Relm α and Ym1 were significantly higher than the controls and their levels at week 1 and 3 were significantly higher than those of week 7,respectively,although no differences were found between week 1,3 and 5.In summary,the F.hepatica induces Th2 bias cellular immune responses at the early stage of infection.Levels of IL-4,Relm α and Ym1 keep the same trend at different time courses.However,high expression of Relm α and Ym1 at week 1 post infection may be affected by complicated factors which need further investigations.%为弄清肝片吸虫感染早期的主要细胞免疫类型及选择性激活巨噬细胞(M2或AAMΦ)标记分子的变化,本试验采用肝片吸虫囊蚴为感染源,经口分别感染雌性BALB/c野生型小鼠,运用特异性PCR鉴定成功感染小鼠后用间接ELISA对腹腔中IL-4和IFN-γ的水平进行测定,并对细胞因子IL-4、转录因子GATA3和M2的标记蛋白Relm a、Ym1分子的mRNA进行荧光定量PCR检测.结果显示,在感染后1,3,5,7周,从所获

  1. NF-κBp50参与IL-4在THP-1细胞中诱导DC-SIGN的表达%NF-κBp50 is Associated With DC-SIGN Expression Induced by IL-4 in THP-1 Cells

    Institute of Scientific and Technical Information of China (English)

    许利军; 常秀春; 姚航平; 吴南屏

    2008-01-01

    DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) is specific receptor on Dendritic cells, and plays a pivotal role on antigens presentation. Uptodate, the clear regulation mechanisms for DC-SIGN expression are not available.IL-4 is one of the most important cytokines inducing DC-SIGN production, while, NF-κB is an important transcription factor controlling signaling transduction. Both IL-4 and NF-κB are closely related to DC-SIGN regulation. NF-κB and IL-4 actions on DC-SIGN promoter activity, DC-SIGN expression as well as interactions between IL-4 and NF-κB were investigated in THP-1 cell. It was found that the mutation of NF-κB binding site in DC-SIGN promoter results in DC-SIGN promoter activity decrease about 50%.NF-κBp50 stimulates DC-SIGN expression in THP-1 cells. IL-4 upregulates DC-SIGN expression on THP-1 cells as well as NF-κB production. These data reveal that NF-κB is associated with IL-4 induced DC-SIGN expression.%树突状细胞表面特异的胞间黏附分子3捕获非整合素(DC-specific intercellular adhesion molecule-3-grabbing nonintegrin,DC-SIGN)是树突状细胞表面特异的蛋白,在抗原呈递过程中起关键作用.这种特异性的表达和DC-SIGN的调节机制有关.到目前为止,DC-SIGN表达调控的机制还不是很清楚.IL-4是诱导DC-SIGN表达的最重要的细胞因子之一,而NF-κB是调控细胞信号转导的一个重要调控因子,两者都和DC-SIGN的表达调节相关.研究了IL-4和NF-κB对DC-SIGN启动子活性、对DC-SIGN表达的影响以及IL-4和NF-κB之间相互作用的关系.发现:DC-SIGN启动子中NF-κB位点缺失可以使DC-SIGN启动子活性下降大约50%,NF-κBp50可以促进DC-SIGN在THP-1细胞的表达,IL-在THP-1细胞诱导DC-SIGN表达的同时,也促进了NF-κBp50的表达.这些结果显示,在THP-1细胞中NF-κBp50参与IL-4诱导的DC-SIGN表达.

  2. IL-2, IFN-γ, IL-4、 IL-6 Expression in Peri-implant Gingival Crevicular Fluid and Clinical Significance%种植体周围炎龈沟液中IL-2、 IFN-γ、IL-4、IL-6的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    郦兴

    2015-01-01

    目的 探讨探讨白细胞介素2、4、6(IL-2、IL-4、IL-6)、干扰素γ(IFN-γ)在种植体周围炎龈沟液(GCF)中的表达及意义.方法 选择2011年6月~2014年6月50例种植体周围炎患者为研究对象.另选择健康种植体患者50例和健康人群50例为对照组.统计3组探诊深度(PD)、龈沟出血指数(SBI)、IL-2、IFN-γ、IL-4、IL-6水平.结果 种植体周围炎组PD、SBI、GCF均高于健康种植体组和对照组,差异有统计学意义(P<0.01);但健康种植体组和对照组PD、SBI、GCF差异无统计学意义(P>0.05);种植体周围炎组IL-2、IFN-γ水平低于健康种植体组和对照组(P<0.01),健康种植体组IL-2、IFN-γ水平低于对照组(P<0.05),种植体周围炎组IL-4、IL-6水平高于健康种植体组和对照组(P<0.01),健康种植体组IL-4、IL-6水平高于对照组(P<0.05);≥60岁组IL-2、IFN-γ水平低于<60岁组(P<0.01),≥60岁组IL-4、IL-6水平高于<60岁组(P<0.01);种植体周围炎患者GCF中IL-2与IFN-γ呈正相关(r=4.267,P=0.016),与IL-4、IL-6分别呈负相关(r=4.352、4.615,P=0.005、0.002),IFN-γ与IL-4、IL-6分别呈负相关(r=4.322、4.603,P=0.009、0.005),IL-4,IL-6呈正相关(r=4.065,P=0.019).结论 种植体周围炎患者IL-4、IL-6高表达,IL-2、IFN-γ低表达,IL-2、IFN-γ、IL-4、IL-6的表达与种植体周围炎患者性别无关,与种植体周围炎患者的年龄有关.

  3. Effects of Prunella vulgaris L. on Expressions of IL-1α,IL-4,IL-8 and TNF-α in Saliva of Patients with Acne%夏枯草对痤疮患者唾液中 IL-1α、IL-4、IL-8和 TNF-α表达的影响

    Institute of Scientific and Technical Information of China (English)

    赵俊茹; 汪文玉; 左付国; 李小茜; 胡冬裴

    2015-01-01

    Objective To detect effects of Prunella vulgaris L. on expressions of IL-1α、IL-4、IL-8 and TNF-α in saliva of patients with acne. Methods 100 patients with severe acne were treated with water extract of Prunella vul-garis L. for a week, 15 g·d-1 each person, including 38Ⅱlevel patients, 27 Ⅲ level patients, 35 Ⅳ level patients. 40 cases of normal people were selected as control. The levels of IL-1α, IL-4, IL-8 and TNF-α were respectively measured before and after treatment by ELISA kits. Results Compared with the control group, the levels of IL-1α, IL-4, IL-8 and TNF-α had different degree of rise. The variability of the population were all Ⅳ level>Ⅲ level>Ⅱ level. The levels of IL-1α, IL-4, IL-8 and TNF-α were significantly decreased. Conclusion The onset of acne was closely related with the expression of IL-1α, IL-4, IL-8 and TNF-α in saliva, illustrating the immune factors played important roles in the onset and development of acne. Further study of the pathogenesis of acne immune mechanism has a guiding significance for clinical diagnosis and therapy, Prunella vulgaris L. may be effective for acne by adjusting peripheral immune factors in patlents with acne.%目的:检测夏枯草对中、重度痤疮患者唾液中白细胞介素1α(interleukin-1α, IL-1α)、白细胞介素4(inter-leukin-4, IL-4)、白细胞介素8(interleukin-8, IL-8)和肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)表达的影响。方法对100例中、重度痤疮患者口服夏枯草水煎液治疗,其中Ⅱ级38例,Ⅲ级27例,Ⅳ级35例,每人每日15 g,连续1周。采集非刺激性全唾液,运用酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)分别检测患者治疗前后及40名正常对照者唾液中 IL-1α、IL-4、IL-8和 TNF-α的表达水平。结果痤疮患者唾液中 IL-1α、IL-4、IL-8和 TNF-α水平较对照组有不同程度的升高,其变化程度均为Ⅳ级

  4. 芪柴煎剂对变应性鼻炎大鼠血清IL-4,IFN-γ影响的实验研究%Effect of Qi Chai decoction on serum IL-4, IFN-γlevel in allergic rhinitis rats

    Institute of Scientific and Technical Information of China (English)

    胥彪; 胡文健

    2015-01-01

    Objective: To study the influence of Qi Chai decoction on serum IL-4, IFN-γ level of allergic rhinitis model of rats so as to explore its role and efficacy in treating allergic rhinitis. Methods:Rats with allergic rhinitis were made by ovalbumin as sensitizing agent. 40 healthy adult SD rats were randomly divided into five groups(8 rats each):normal control group low-dose and high dose Qi Chai decoction groups,loratadine group, and model control group. Corresponding mjodel control given for 14 consecutive days in each group. Then the serum IL-4 and IFN-γ contents were tested by ELISA. Results: Compared with model control group,the serum IL-4 levels of low dose and high dose Qi Chai decoction groups and desloratadine group were significantly lower, and there were significant differences (P<0.05), and IL-4 level of low dose Qi Chai decoction group was higher than that of high dose group (P< 0.05). Compared with model control group, the serum IFN-γ level of low dose and high dose Qi Chai decoction groups, and the desloratadine group were significantly higher (P< 0.05). Compared with high dose group, the serum IFN-γ level of low dose Qi Chai decoction group and loratadine group were significantly lower (P< 0.05). Conclusion: The Qi Chai decoction can down-regulate the serum IL-4 levels and up-regulate the serum IFN-γlevels of the rats with allergic rhinitis.%目的::研究芪柴煎剂(自拟方)对变应性鼻炎大鼠模型血清IL-4、IFN-γ的影响,探讨其对变应性鼻炎大鼠的作用疗效。方法:应用卵清蛋白将实验大鼠制作成变应性鼻炎模型,随机分为正常对照组(A组)、芪柴煎剂低剂量组(B组)、高剂量组(C组)、地氯雷他定组(D组)、模型对照组(E组)各8只。连续14 d分别给予对应的药物,A组、E组以蒸馏水替代。用双抗体夹心ELISA法检测血清IL-4、IFN-γ的含量。结果:各实验组血清IL-4含量较模型对照组明显偏低,差异均有统计学意义(P<0.05)

  5. ICH 患者血清和血肿液中 IL-4、IL-6、IL-8、IL-10的变化研究%Hematoma fluid and serum of patients with acute cerebral hemorrhage about IL-4, IL-6, IL-8, and IL-10 Changes

    Institute of Scientific and Technical Information of China (English)

    赵金安; 白西民

    2016-01-01

    目的:观察急性脑出血(ICH)患者血清和血肿液中 IL-4、IL-6、IL-8、IL-10的变化。方法:选取80例在我院治疗的基底节区脑出血患者,按照发病时间将患者分为5组(发病时间≤6h、6h <发病时间≤12h、12h <发病时间≤24h、24h <发病时间≤72h、3d <发病时间≤7d),检测各组血清和血肿液中 IL-4、IL-6、IL-8、IL-10的含量以及出血量和水肿量;另选取21例健康体检者,检测其血清 IL-4、IL-6、IL-8、IL-10的含量作对照。结果:IL-4、IL-6、IL-8、IL-10在患者静脉血、血肿液中的浓度均显著高于正常对照组,而患者静脉血与血肿液中 IL-4、IL-6、IL-8、IL-10浓度比较,差异无统计学意义。基底节区脑出血患者发病时间≤6h 与正常对照组比较,除 IL-10浓度升高不明显外,IL-4、IL-6、IL-8浓度均明显升高;24h <发病时间≤72h 时,IL-4、IL-6、IL-8浓度与其他各时段比较,以及3d <发病时间≤7d时,IL-10浓度与其他各时段比较,差异均具有统计学意义。各时段出血量和水肿量比较,差异均无统计学意义,出血量和水肿量均在发病时间≤6h至12h <发病时间≤24h 逐渐增大,12h <发病时间≤24h 达到峰值。结论:ICH 患者静脉血、血肿液中 IL-4、IL-6、IL-8浓度可以作为早期检测(≤6h)ICH 的指标,并可通过不同炎症因子的含量变化判断 ICH 患者发病时间,且患者发病一周内周围脑组织出血量和水肿量变化不大。%Objective To observe the changes of IL-4, IL-6, IL-8, IL-10 in serum and hematoma of ICH. Methods 80 cases ICH patients were divided into five groups(<6h, 6-12h, 12-24h, 24-72h, 3-7d). The control group were 21 healthy persons serum. The content of IL-4, IL-6, IL-8, IL-10 in different time were compared and the amount of bleeding and edema. Results IL-4, IL-6, IL-8, IL-10 in patients with venous hematoma fluid concentrations were

  6. An IL-4R alpha allelic variant, I50, acts as a gain-of-function variant relative to V50 for Stat6, but not Th2 differentiation.

    Science.gov (United States)

    Stephenson, Linda; Johns, Mary H; Woodward, Emily; Mora, Ana L; Boothby, Mark

    2004-10-01

    Signaling through the IL-4R alpha-chain (IL-4Ralpha) is crucial for the development of Th2 cells, central effectors in atopic disease. Alleles of the IL-4Ralpha have been identified that have been variably associated with increased incidence of allergic disease, but there is little direct evidence that any variant is sufficient to alter a target that determines allergic pathophysiology or susceptibility. Variants of IL-4Ralpha encoding isoleucine instead of valine at position 50 (I50 vs V50, respectively) can signal increased Stat6-dependent transcriptional activity, whether in an I50, Q551 or I50, R551 haplotype. Strikingly, signaling through these receptors did not increase the efficiency of Th2 development or the IL-4 mediated repression of Th1 development or a target gene, IL-18Ralpha. Further, IL-4-induced proliferation was similar for Th2 cells independent of the variant expressed. Together these findings indicate that IL-4Ralpha variants that exhibit gain-of-function with respect to Stat6 do not act directly through alterations in Th2/Th1 induction after Ag exposure. The data further suggest that for such variants, any mechanistic involvement is based on a role in cellular targets of Th2 cytokines.

  7. Bronchial macrophages in asthmatics reveal decreased CD16 expression and substantial levels of receptors for IL-10, but not IL-4 and IL-7.

    Directory of Open Access Journals (Sweden)

    Milena Dabrowska

    2007-10-01

    Full Text Available The role of different subpopulations of bronchial macrophages (BMs in asthma pathogenesis has not yet been completely elucidated. In addition, little is known about potential in vivo responsiveness of BMs to pro- and anti-inflam-matory cytokines present in the bronchial milieu. We aimed to characterize asthmatic patients' BM subpopulations delineated by common markers of macrophage/monocyte cells, CD16 and CD14, and subsequently to analyze cytokine receptor expression on those subsets. Subjects included eighteen patients with moderate asthma (six steroid-naive and twelve steroid-treated and ten healthy control subjects. Flow cytometry was used to analyze phenotypical features of BMs including expression of receptors for IL-10, IL-4 and IL-7. Exhaled nitric oxide analysis and induced sputum eosinophil counts were used to assess airway inflammation. BMs from both steroid-naive and steroid-treated asthmatic patients showed significantly decreased expression of CD16, as compared to healthy subjects' BMs. CD16, but not CD14, expression inversely correlated with exhaled nitric oxide levels and sputum eosinophilia. Short-term administration of inhaled cortiocosteroids (ICS in steroid-naive asthmatic patients led to significant reduction of CD16 expression and enhancement of CD14 expression. Next, we analyzed the expression of receptors for IL-10, IL-4 and IL-7 on the surface of BM subpopulations characterized by different levels of CD14 and CD16 expression. We observed substantial levels of IL-10R on the surface of BMs collected from asthmatic and healthy subjects. Interestingly, IL-10R was found mostly on those macrophages that co-expressed CD14. In contrast, independently on co-expression of CD14, the levels of IL-4R and IL-7R on BMs were low in both asthmatic and healthy subjects. The results suggest that different BM subsets may be differentially involved in regulating the inflammatory response in allergic asthma.

  8. Plasma levels of TNF-α, IFN-γ, IL-4 and IL-10 during a course of experimental contagious bovine pleuropneumonia

    Directory of Open Access Journals (Sweden)

    Sacchini Flavio

    2012-04-01

    Full Text Available Abstract Background Contagious Bovine Pleuropneumonia (CBPP, caused by Mycoplasma mycoides subsp. mycoides, is widespread in sub-Saharan Africa. The current live vaccine T1/44 has limited efficacy and occasionally leads to severe side effects in the animals. A better understanding of the immune responses triggered by Mycoplasma mycoides subsp. mycoides and their role in disease progression will help to facilitate the design of a rational vaccine. Currently, knowledge of cytokines involved in immunity and immunopathology in CBPP is rather limited. The aim of this study was to characterize the in vivo plasma concentrations of the cytokines TNF-α, IFN-γ, IL-4, IL-10 and the overall role of CD4+ T cells in the development of cytokine levels during a primary infection. Plasma cytokine concentrations in two groups of cattle (CD4+ T cell-depleted and non-depleted cattle experimentally infected with Mycoplasma mycoides subsp. mycoides were measured and their relationship to the clinical outcomes was investigated. Results Plasma cytokine concentrations varied between animals in each group. Depletion of CD4+ T cells did not induce significant changes in plasma levels of TNF-α, IL-4, and IL-10, suggesting a minor role of CD4+ T cells in regulation or production of the three cytokines during the time window of depletion (1-2 weeks post depletion. Unexpectedly, the IFN-γ concentrations were slightly, but statistically significantly higher in the depleted group (p + T cell-depleted animals that experienced severe disease, had high levels of TNF-α and IFN-γ. Only one severely diseased non-depleted animal showed a high serum concentration of IL-4 post infection. Conclusions Comparison of most severely diseased animals, which had to be euthanized prior to the expected date, versus less severe diseased animals, irrespective of the depletion status, suggested that high TNF-α levels are correlated with more severe pathology in concomitance with high IFN

  9. TET1 and TET3 are essential in induction of Th2-type immunity partly through regulation of IL-4/13A expression in zebrafish model.

    Science.gov (United States)

    Yang, Chao; Li, Zhuo; Kang, Wei; Tian, Yu; Yan, Yuzhu; Chen, Wei

    2016-10-10

    It has been considered that epigenetic modulation can affect a diverse array of cellular activities, in which ten eleven translocation (TET) methylcytosine dioxygenase family members refer to a group of fundamental components involved in catalyzation of 5-hydroxymethylcytosine and modification of gene expression. Even though the function of TET proteins has been gradually revealed, their roles in immune regulation are still largely unknown. Recent studies provided clues that TET2 could regulate several innate immune-related inflammatory mediators in mammals. This study sought to explore the function of TET family members in potential T-helper (Th) cell differentiation involved in adaptive immunity by utilizing a zebrafish model. As shown by results, soluble antigens could induce expression of zebrafish IL-4/13A (i.e. a pivotal Th2-type cytokine essential in Th2 cell differentiation and functions), and further trigger the expression of Th1- and Th2-related genes. It is noteworthy that this response was accompanied by the up-regulation of two TET family members (TET1 and TET3) both in immune organs (spleen and kidney) and cells (peripheral lymphocytes). Knocking-down of TET1 and TET3 will give rise to the decreased responses of IL-4/13A induction against exogenous soluble antigen stimulation, and further restrain the expression of Th2-related genes, which indicates a restrained Th2 cell differentiation. Nonetheless, TET2 did not exhibit effect on the modification of Th1/Th2 related gene expression. Hence, these data showed that TET1 and TET3 might be two significant epigenetic regulators involved in Th2 differentiation through regulation of IL-4/13A expression. This is the first report to show that TET family members play indispensable roles in Th2-type immunity, indicating an epigenetic modulation manner involved in adaptive immune regulations and responses. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Oral Administration of T Cell Epitope Peptide Inhibits the Systemic IL-4 Response Elicited by an Egg-White Diet in a TCR Transgenic Mouse Model

    OpenAIRE

    HIRAIDE, Erika; NAKAJIMA-ADACHI, Haruyo; Hachimura, Satoshi

    2014-01-01

    Oral immunotherapy with T cell epitope peptides is a promising treatment for food allergy. We examined the effect of oral administration of an ovalbumin T cell epitope peptide (OVA323-339) in a TCR transgenic mouse model (OVA23-3 mice). OVA23-3 mice were fed egg-white diet containing ovalbumin and subsequently orally administrated the OVA323-339 peptide. Cytokine measurements revealed that the IL-4 production of splenic CD4+ T cells was significantly decreased by feeding the OVA323-339 peptid...

  11. Four-locus gene interaction between IL13, IL4, FCER1B, and ADRB2 for asthma in Chinese Han children.

    Science.gov (United States)

    Hua, Li; Zuo, Xian-Bo; Bao, Yi-Xiao; Liu, Quan-Hua; Li, Jing-Yang; Lv, Jie; Fang, Ding-Zhu; Lin, Qian; Bao, Jun; Ji, Ruo-Xu

    2016-04-01

    IL13, IL4, IL4RA, FCER1B, and ADRB2 are important inflammatory genes associated with immunoglobulin E levels. This study attempts to determine whether there are gene-gene interactions in the five genes among asthmatic children of Chinese Han nationality. Nine single-nucleotide polymorphisms (SNPs) in the five genes were genotyped in 1,000 asthmatic children and 1,000 healthy controls using TaqMan real-time quantitative polymerase chain reaction. Multifactor-dimensionality reduction method was applied for the analysis. A four-way gene-gene interaction model consisting of IL13 rs20541, IL4 rs2243250, ADRB2 rs1042713, and FCER1B rs569108 was chosen as the optimal one for determining asthma susceptibility (testing balanced accuracy = 0.6089, cross-validation consistency = 10/10, P = 6.98E-05). Each of the four SNPs was identified to have an independent association with childhood asthma (G allele of rs20541, odds ratio (OR) = 1.24, P = 1.23E-03; T allele of rs2243250, OR = 1.25, P = 3.81E-03; A allele of rs1042713, OR = 1.29, P = 6.75E-05; G allele of rs569108, OR = 1.27, P = 3.86E-03). Individuals homozygous for the risk alleles at all the four loci (rs20541 GG, rs2243250 TT, rs1042713 AA, and rs569108 GG) had a significantly higher risk of asthma compared with those without any risk homozygotes (OR = 13.55, P = 4.28E-03), and also greater than those with less than four risk homozygotes (OR = 10.09, P = 6.51E-03). Our results suggest that IL13 rs20541, IL4 rs2243250, ADRB2 rs1042713, and FCER1B rs569108, four SNPs with significant sole effect on asthma, interact to confer a higher risk for the disease in Chinese Han children. © 2015 Wiley Periodicals, Inc.

  12. Cytokine responses to Schistosoma haematobium in a Zimbabwean population: contrasting profiles for IFN-γ, IL-4, IL-5 and IL-10 with age

    Directory of Open Access Journals (Sweden)

    Mduluza Takafira

    2007-11-01

    Full Text Available Abstract Background The rate of development of parasite-specific immune responses can be studied by following their age profiles in exposed and infected hosts. This study determined the cytokine-age profiles of Zimbabweans resident in a Schistosoma haematobium endemic area and further investigated the relationship between the cytokine responses and infection intensity. Methods Schistosome adult worm antigen-specific IFN-γ, IL-4, IL-5 and IL-10 cytokine responses elicited from whole blood cultures were studied in 190 Zimbabweans exposed to S. haematobium infection (aged 6 to 40 years old. The cytokines were measured using capture ELISAs and the data thus obtained together with S. haematobium egg count data from urine assays were analysed using a combination of parametric and nonparametric statistical approaches. Results Age profiles of schistosome infection in the study population showed that infection rose to peak in childhood (11–12 years followed by a sharp decline in infection intensity while prevalence fell more gradually. Mean infection intensity was 37 eggs/10 ml urine (SE 6.19 eggs/10 ml urine while infection prevalence was 54.7%. Measurements of parasite-specific cytokine responses showed that IL-4, IL-5 and IL-10 but not IFN-γ followed distinct age-profiles. Parasite-specific IL-10 production developed early, peaking in the youngest age group and declining thereafter; while IL-4 and IL-5 responses were slower to develop with a later peak. High IL-10 producers were likely to be egg positive with IL-10 production increasing with increasing infection intensity. Furthermore people producing high levels of IL-10 produced little or no IL-5, suggesting that IL-10 may be involved in the regulation of IL-5 levels. IL-4 and IFN-γ did not show a significant relationship with infection status or intensity and were positively associated with each other. Conclusion Taken together, these results show that the IL-10 responses develop early

  13. Effects of Blockage of IL-4Rα on the Early Cytokine Profiles in Hepatic Mononuclear Cells from Mice Infected with Fasciola hepatica%IL-4受体阻断对小鼠急性感染肝片吸虫后肝脏单核细胞悬液中细胞因子的影响

    Institute of Scientific and Technical Information of China (English)

    罗洪林; 王豪举; 张文韬; 郭智莉; 周雪梅; 周容琼; 周作勇

    2013-01-01

    本研究旨在探索肝片吸虫感染小鼠急性期肝脏单核细胞悬液中细胞因子表达模式及其原因.试验将小鼠分为4组,分别对感染抗体处置组、感染非抗体处置组、抗体处置非感染组和非抗体处置非感染组的肝脏单核细胞培养上清液中IL-4、IL-5、IL-13及IFN-γ进行测定;同时也对肝脏中IL-4及IL-12P40 mRNA水平进行荧光定量PCR检测.结果显示,IL-4和IL-5的表达模式相似.在非感染状态下,无论是否进行抗体处置,两者都处于较低表达水平.在感染状态下,两者在非抗体处置小鼠中的表达显著高于抗体处置组(P<0.05).IL-13与IL-4及IL-5的表达差异在于感染并用抗体处置后,小鼠肝脏单核细胞中的IL-13仍有较高水平表达.IFN-γ的表达量在感染后有所增加,但在有无抗体处理间无显著差异(P>0.05).mRNA检测结果显示,在非感染状态下,抗体处置后的IL-4 mRNA水平显著低于非抗体处置组(P<0.05).感染后非抗体处置组小鼠中IL-4 mRNA水平极显著高于抗体处置组(P<0.01),同时也极显著高于非感染非抗体处置组(P<0.01).IL-12P40 mRNA的水平在感染状态下,抗体处置组的IL 12P40 mRNA虽较非抗体处置组低,但无显著差异(P>0.05).但感染后非抗体处置组的IL-12P40 mRNA水平均极显著高于感染组抗体处置和非抗体处置组(P<0.01).本试验结果表明,IL-4Rα对肝片吸虫感染急性期IL5和IL-4的表达极其重要,但对IL-13及IFN-γ的影响较小.%The assay was aimed to explore the early cytokine profiles in hepatic mononuclear cell from mice infected with Fasciola hepatica. Mice were classed into 2 groups, infected and non-infected. In each group, mice were treated or untreated with IL-4R α antibodies, respectively. Hepatic mononuclear cells were harvested and cultured. The supernatant was used to measure the cytokine levels and the livers were used to measure mRNA of IL-4 and IL-12P40 by Real-time PCR. Results

  14. THE EFFECTS OF IL-1 AND IL-4 ON THE EPO-INDEPENDENT ERYTHROID PROGENITOR IN POLYCYTHEMIA-VERA

    NARCIS (Netherlands)

    DEWOLF, JTM; HENDRIKS, DW; ESSELINK, MT; HALIE, MR; VELLENGA, E

    1994-01-01

    Human recombinant interleukin-1 (IL-1) was studied for its effects on the erythroid progenitors from normal subjects and from patients with polycythaemia vera (PV). No supportive effect of IL-1 was noticed on the normal, erythropoietin (Epo) dependent, erythroid burst-forming unit (BFU-E) using peri

  15. ImmunemiR - a database of prioritized immune miRNA disease associations and its interactome.

    Science.gov (United States)

    Prabahar, Archana; Natarajan, Jeyakumar

    2017-01-17

    MicroRNAs are the key regulators of gene expression and their abnormal expression in the immune system may be associated with several human diseases such as inflammation, cancer and autoimmune diseases. Elucidation of microRNA (miRNA) disease association through the interactome will deepen the understanding of its disease mechanisms. In this present study, miRNAs specific to immune related diseases were retrieved from curated databases and literature based on MeSH classification of immune system diseases. In total 245 immune miRNAs associated with 92 OMIM disease categories were identified and they are prioritized to specific immune diseases using random walk ranking algorithm. These data were compiled as ImmunemiR, a database of prioritized immune miRNA disease associations. This database provides both text based annotation information and network visualization of its interactome network. To our knowledge, ImmunemiR is the first available database to provide a comprehensive repository of human immune disease associated miRNAs with network visualization options of its target genes, protein-protein interactions (PPI).

  16. IL-4 inhibits TNF-α-mediated osteoclast formation by inhibition of RANKL expression in TNF-α-activated stromal cells and direct inhibition of TNF-α-activated osteoclast precursors via a T-cell-independent mechanism in vivo.

    Science.gov (United States)

    Fujii, Toshiya; Kitaura, Hideki; Kimura, Keisuke; Hakami, Zaki Weli; Takano-Yamamoto, Teruko

    2012-10-01

    It has been reported that osteoclastogenesis is induced by tumor necrosis factor (TNF)-α. Interleukin (IL)-4 is the most important cytokine involved in humoral immunity. However, no studies have investigated the effect of IL-4 on TNF-α-mediated osteoclast formation in vivo. In this study, we investigated the effect of IL-4 on TNF-α-mediated osteoclast formation in vivo. TNF-α was administered with and without IL-4 into the supracalvariae of mice. The number of osteoclasts and the levels of mRNA for cathepsin K and tartrate-resistant acid phosphate, both osteoclast markers, in mice administered TNF-α and IL-4 were lower than those in mice administered TNF-α alone. The level of tartrate-resistant acid phosphatase form 5b (TRACP5b) as a marker of bone resorption in mice administered both TNF-α and IL-4 was also lower. We showed that IL-4 inhibited TNF-α-mediated osteoclast formation in osteoclast precursors in vitro. Expression of receptor activator of NF-κB ligand (RANKL) in TNF-α-activated stromal cells was also inhibited. Furthermore, we investigated whether IL-4 had effects on both stromal cells and osteoclast precursors in TNF-α-mediated osteoclast formation in vivo. Using mice whose stromal cells and osteoclast precursors were chimeric for the presence of TNF receptors, IL-4 inhibited TNF-α-mediated osteoclast formation in the presence of TNF-α-responsive stromal cells, and TNF-α-responsive osteoclast precursors in vivo. IL-4 also inhibited TNF-α-induced RANKL expression in the presence of TNF-α-responsive stromal cells in vivo. This event is dependent on p38 inhibition in vitro. Additionally, IL-4 inhibited TNF-α-mediated osteoclast formation in T cell-depleted mice. In summary, we conclude that IL-4 inhibited TNF-α-mediated osteoclast formation by inhibiting expression of RANKL in TNF-α-activated stromal cells, and directly inhibited TNF-α-activated osteoclast precursors in vivo via a T cell-independent mechanism.

  17. Systematic localization of common disease-associated variation in regulatory DNA.

    Science.gov (United States)

    Maurano, Matthew T; Humbert, Richard; Rynes, Eric; Thurman, Robert E; Haugen, Eric; Wang, Hao; Reynolds, Alex P; Sandstrom, Richard; Qu, Hongzhu; Brody, Jennifer; Shafer, Anthony; Neri, Fidencio; Lee, Kristen; Kutyavin, Tanya; Stehling-Sun, Sandra; Johnson, Audra K; Canfield, Theresa K; Giste, Erika; Diegel, Morgan; Bates, Daniel; Hansen, R Scott; Neph, Shane; Sabo, Peter J; Heimfeld, Shelly; Raubitschek, Antony; Ziegler, Steven; Cotsapas, Chris; Sotoodehnia, Nona; Glass, Ian; Sunyaev, Shamil R; Kaul, Rajinder; Stamatoyannopoulos, John A

    2012-09-07

    Genome-wide association studies have identified many noncoding variants associated with common diseases and traits. We show that these variants are concentrated in regulatory DNA marked by deoxyribonuclease I (DNase I) hypersensitive sites (DHSs). Eighty-eight percent of such DHSs are active during fetal development and are enriched in variants associated with gestational exposure-related phenotypes. We identified distant gene targets for hundreds of variant-containing DHSs that may explain phenotype associations. Disease-associated variants systematically perturb transcription factor recognition sequences, frequently alter allelic chromatin states, and form regulatory networks. We also demonstrated tissue-selective enrichment of more weakly disease-associated variants within DHSs and the de novo identification of pathogenic cell types for Crohn's disease, multiple sclerosis, and an electrocardiogram trait, without prior knowledge of physiological mechanisms. Our results suggest pervasive involvement of regulatory DNA variation in common human disease and provide pathogenic insights into diverse disorders.

  18. Infliximab in Crohn's disease-associated toxic megacolon

    NARCIS (Netherlands)

    Geenen, E.J.M. van; Sachar, D.B.

    2012-01-01

    Refractory medical treatment of Crohn disease-associated toxic megacolon usually requires surgery, which carries substantial morbidity and mortality. We report a case of a woman with steroid and antibiotic-refractory fulminant Crohn colitis and ileitis, complicated by a toxic megacolon, who was

  19. Infliximab in Crohn's disease-associated toxic megacolon

    NARCIS (Netherlands)

    Geenen, E.J.M. van; Sachar, D.B.

    2012-01-01

    Refractory medical treatment of Crohn disease-associated toxic megacolon usually requires surgery, which carries substantial morbidity and mortality. We report a case of a woman with steroid and antibiotic-refractory fulminant Crohn colitis and ileitis, complicated by a toxic megacolon, who was succ

  20. Cesarean section and disease associated with immune function

    DEFF Research Database (Denmark)

    Kristensen, Kim; Stokholm, Lonny Merete

    2016-01-01

    BACKGROUND: Earlier studies have shown that delivery by cesarean section (CS) is associated with an increased risk of disease associated with immune function in the offspring, but these studies have generally not discriminated between the effect of acute and elective CS. OBJECTIVE: We sought to f...

  1. National Tay-Sachs and Allied Diseases Association, Inc.

    Science.gov (United States)

    Exceptional Parent, 1977

    1977-01-01

    Reviewed are the history and organization, purpose and programs, and public services of the National Tay-Sachs and Allied Diseases Association, an organization geared toward eradicating Tay-Sachs disease (a hereditary disorder affecting primarily Jewish infants which generally leads to deterioration and death by the child's fifth year). (SBH)

  2. The National Tay Sachs and Allied Diseases Association.

    Science.gov (United States)

    Zeitlin, Paula

    1986-01-01

    The National Tay-Sachs and Allied Diseases Association is involved in education, research, and prevention of Tay-Sachs, an inherited metabolic disorder which destroys the central nervous system, and over 30 related disorders. The group features a parent peer group network and a support group for carrier couples. (CL)

  3. The National Tay Sachs and Allied Diseases Association.

    Science.gov (United States)

    Zeitlin, Paula

    1986-01-01

    The National Tay-Sachs and Allied Diseases Association is involved in education, research, and prevention of Tay-Sachs, an inherited metabolic disorder which destroys the central nervous system, and over 30 related disorders. The group features a parent peer group network and a support group for carrier couples. (CL)

  4. National Tay-Sachs and Allied Diseases Association, Inc.

    Science.gov (United States)

    Exceptional Parent, 1977

    1977-01-01

    Reviewed are the history and organization, purpose and programs, and public services of the National Tay-Sachs and Allied Diseases Association, an organization geared toward eradicating Tay-Sachs disease (a hereditary disorder affecting primarily Jewish infants which generally leads to deterioration and death by the child's fifth year). (SBH)

  5. Disease associated time consumption in early rheumatoid arthritis

    NARCIS (Netherlands)

    Kuper, IH; Prevoo, MLL; van Leeuwen, MA; van Riel, PLCM; Lolkema, WF; Postma, DS; van Rijswijk, MH

    2000-01-01

    Objective. To quantify the disease associated time consumption of normal activities of daily living and of treatment and monitoring activities in a cohort of patients with early rheumatoid arthritis (RA) with followup of at least 6 years. Comparison was made with a group of patients with asthma and

  6. Optimisation of the CT h4S bioassay for detection of human interleukin-4 secreted by mononuclear cells stimulated by phytohaemaglutinin or by human leukocyte antigen mismatched mixed lymphocyte culture

    DEFF Research Database (Denmark)

    Petersen, Søren Lykke; Russell, Charlotte Astrid; Bendtzen, Klaus

    2002-01-01

    Limiting dilution analysis has been used in the context of allogeneic bone marrow transplantation to determine anti-recipient interleukin-2 (IL-2) producing helper T lymphocyte precursor (HTLp) frequencies, which in several studies have been predictive of graft-versus-host disease (GVHD). Recently...... of IL-4 detection was not due to high amounts of soluble IL-4 receptor. With the use of 1x10(6) responder cells/well in HLA-mismatched MLC, we found limited IL-4 accumulation still increasing at day 12. We conclude that the CT.h4S bioassay is a reliable and specific method for quantification of IL-4...... accumulation in cultures of human MNC. The difference in optimal timing for IL-2 (day 3) and IL-4 (>/=day 12) detection and evidence of very low IL-4 producing HTLp frequencies makes the relevance of a combined IL-2/IL-4 HTLp assay questionable....

  7. Research on Change of Levels of IL-4,IL-5,IL-12,and Total IgE in adult Asthmatic%成人哮喘患者血清IL4、IL5、IL12及IgE水平的变化

    Institute of Scientific and Technical Information of China (English)

    黄建宏; 郭欣然; 钟世湖; 翁育清; 许文; 林虹; 黄琳

    2004-01-01

    目的研究成人哮喘患者白细胞介素4(IL 4)、白细胞介素5(IL 5)白细胞介素12(IL 12)、与免疫球蛋白E(IgE)水平的变化.方法成人哮喘患者60例,随机分为:发作组30例;缓解组30例;健康对照组40例.分别检测血清IL 4、IL 5、IL 12与IgE(ELISA法)水平.结果发作组血清IL 4、IL 5水平明显高于缓解组,有显著性差异(P<0.05),缓解组血清IL 4、IL 5水平明显高于对照组,有显著性差异(P<0.01);发作组血清IL 12水平明显低于缓解组,有显著性差异(P<0.05),缓解组血清IL 12水平明显低于对照组,有显著性差异(P<0.01);发作组血清IgE水平明显高于缓解组,有显著性差异(P<0.05),缓解组血清IgE水平明显高于对照组,有显著性差异(P<0.01).成人哮喘患者血清IL 4、lL 5水平与IgE呈正相关(P<0.01),成人哮喘患者血清IL 12水平与IgE呈负相关(P<0.01).结论成人哮喘患者血清IL 4、IL 5和IgE水平升高,IL 12水平降低,表明哮喘是一种慢性气道炎症,在缓解期仍需抗炎治疗.

  8. Mutations of SURF-1 in Leigh disease associated with cytochrome c oxidase deficiency.

    OpenAIRE

    1998-01-01

    Leigh disease associated with cytochrome c oxidase deficiency (LD[COX-]) is one of the most common disorders of the mitochondrial respiratory chain, in infancy and childhood. No mutations in any of the genes encoding the COX-protein subunits have been identified in LD(COX-) patients. Using complementation assays based on the fusion of LD(COX-) cell lines with several rodent/human rho0 hybrids, we demonstrated that the COX phenotype was rescued by the presence of a normal human chromosome 9. L...

  9. Dual Roles of IFN-γ and IL-4 in the Natural History of Murine Autoimmune Cholangitis: IL-30 and Implications for Precision Medicine.

    Science.gov (United States)

    Syu, Bi-Jhen; Loh, Chia-En; Hsueh, Yu-Hsin; Gershwin, M Eric; Chuang, Ya-Hui

    2016-10-10

    Primary biliary cirrhosis (PBC) is a progressive autoimmune liver disease with a long natural history. The pathogenesis of PBC is thought to be orchestrated by Th1 and/or Th17. In this study, we investigated the role of CD4(+) helper T subsets and their cytokines on PBC using our previous established murine model of 2-OA-OVA immunization. We prepared adeno-associated virus (AAV)-IFN-γ and AAV-IL-4 and studied their individual influences on the natural history of autoimmune cholangitis in this model. Administration of IFN-γ significantly promotes recruitment and lymphocyte activation in the earliest phases of autoimmune cholangitis but subsequently leads to downregulation of chronic inflammation through induction of the immunosuppressive molecule IL-30. In contrast, the administration of IL-4 does not alter the initiation of autoimmune cholangitis, but does contribute to the exacerbation of chronic liver inflammation and fibrosis. Thus Th1 cells and IFN-γ are the dominant contributors in the initiation phase of this model but clearly may have different effects as the disease progress. In conclusion, better understanding of the mechanisms by which helper T cells function in the natural history of cholangitis is essential and illustrates that precision medicine may be needed for patients with PBC at various stages of their disease process.

  10. Anti-inflammatory/regulatory cytokine microenvironment mediated by IL-4 and IL-10 coordinates the immune response in hemophilia A patients infected chronically with hepatitis C virus.

    Science.gov (United States)

    Pimentel, João Paulo; Chaves, Daniel Gonçalves; Araújo, Ana Ruth Silva; de Araújo, Erbênia Maria Martins; da Silva Fraporti, Liziara; Neves, Walter Luiz Lima; Tarragô, Andrea Monteiro; Torres, Katia Luz; Gentz, Solange Henschke Lima; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis; Malheiro, Adriana

    2013-06-01

    In the past decades patients with hemophilia were infected commonly by hepatitis C virus (HCV) and a significant number of patients are infected chronically. Focusing on the role of the immune system for controlling and or maintaining HCV infection, the leukocyte and cytokine profiles of peripheral blood from hemophilia A patients and other patients with and without HCV infection were studied. The results demonstrated that hemophilia A is characterized by a general state of circulating leukocytes activation along with an overall increase in the frequency of IL-6 and IL-10 with decrease of IL-8 and IL-12. HCV infection of patients with hemophilia A does not influence further the activation state of circulating leukocytes but is accompanied by lower levels of alanine transaminase (ALT) and a prominent anti-inflammatory/regulatory serum cytokine pattern, mediated by IL-4 and IL-10. Additionally, the results demonstrated that hemophilia A patients infected with HCV displaying No/Low antibody response to C33c and C22 have significant lower viral load and higher serum levels of IL-12 and IL-4. This finding suggests that the differential RIBA reactivity to C33c/C22 HCV core proteins may have a putative value as a prognostic biomarker for the infection in hemophilia A patients.

  11. [Bone marrow mesenchymal stem cells modulated the inflammatory response by regulating the expression of IL-4 and RAGE products in the rats with MODS].

    Science.gov (United States)

    Zhou, Xia; Xiu, Guanghui; Zhu, Yichao; Chen, Xiaolei; Xiong, Wei; Pan, Xinghua; Sun, Jie; Ling, Bin

    2017-04-01

    To investigate the underlying mechanism of bone marrow mesenchymal stem cells (BMSC) modulating the inflammatory response during the multiple organ dysfunction syndrome (MODS), especially the expression of inflammatory cytokines, which will provide new theoretical and experimental basis of MODS in clinic. BMSC of Sprague-Dawley (SD) rat (female, 4 weeks) was extracted and cultivated, and the 4th passage were used in experimental study. According to the random number table, 60 female SD rats were divided into three groups (n = 20 per group): sham group, MODS group, BMSC group. MODS model in rats was induced by lipopolysaccaride (LPS, 1 mg/kg) via femoral vein injection. Sham group was injected with the sterile phosphate buffer saline (PBS) in the same volume. BMSC group, in which BMSC infusion was started at 2 hours after 0.5 mL LPS stimulation (1×10(6)/cells) through the tail vein. The survival rate was observed after 72 hours in each group. Abdominal aortic blood was collected for routine blood and biochemical examination at 72 hours after operation. Protein microarray was used to detect the related 34 inflammatory cytokines. Signal ratio was defined as the differentially expressed factors when it was more than 2.0 or less than 0.5. And enzyme linked immunosorbent assay (ELISA) was be applied to validate the significant inflammation factor. Meanwhile, the heart, kidney, intestine tissue was harvested, then their pathological changes were observed by hematoxylin eosin (HE) staining. 20, 12, 16 rats lived in sham group, MODS group and BMSC group respectively at 72 hours after operation. Compared with the sham group, the indicators (routine blood, liver and kidney function, myocardial enzyme) were apparently unusual, and the heart, kidney, intestine tissue were injured obviously in the MODS group. After BMSC administration, the organ function was improved and tissue damaged was alleviated significantly. Protein microarray showed that interleukin-4 (IL-4) and

  12. Effects of triptolide on the expression of intestinal mucosa IL-4 and IL-13 in experi-mental colitis rats%雷公藤甲素对大鼠实验性结肠炎组织中IL-4、IL-13表达的影响

    Institute of Scientific and Technical Information of China (English)

    杨立; 肖明明; 桑力轩; 李岩; 邢煜; 王岩; 姚远

    2015-01-01

    目的 探讨雷公藤甲素对三硝基苯磺酸钠( TNBS)诱导的大鼠结肠炎的疗效,以及对炎性细胞因子IL-4、IL-13表达的影响. 方法 成年SD大鼠18只,随机分为正常对照组( C组)、TNBS模型组( D1组)、雷公藤甲素组( TP组). 观察大鼠的一般情况,比较结肠组织炎症程度. HE染色观察大鼠结肠组织形态学变化.用反转录聚合酶链反应( RT-PCR)和Western blot( WB)法检测大鼠结肠组织IL-4和IL-13的表达水平. 结果PCR和WB法检测结果表明,C组结肠组织 IL-4、IL-13 的表达水平最高,D1 组表达最低,TP组介于两者之间.结论 雷公藤甲素能有效治疗TNBS诱导的大鼠结肠炎,其作用机制可能与雷公藤甲素上调大鼠结肠黏膜抑炎因子IL-4、IL-13的表达,抑制炎症的发生发展有关.%Objective To evaluate the curative effect of triptolide on TNBS induced colitis and the expression of intestinal mucosa IL-4 and IL-13 in experimental colitis rats and to investigate the underlying mechanisms. Methods 18 adult Sprague-Dawley rats were randomized into three groups:normal control group ( group C ) , model group (group D1),tripotlide treatment group (group TP). The general status of the rats was observed,and the histopathologic changes in the colon were examined. Reverse transcription-polymerase chain reaction ( PCR) and Western blot ( WB) techniques were used to detect the expression of IL-4 and IL-13. Results PCR and WB methods showed that the ex-pression levels of IL-4 and IL-13 in group C were higher than those of group D1 and group TP(P<0. 05),and the ex-pression levels in group D1 were lover than those of group TP ( P<0. 05). Conclusion Triptolide could effectively improve the TNBS-induced colitis in rats by promoting the expression of IL-4 and IL-13 and inhibiting the development of inflammation.

  13. 过敏性哮喘患者外周血IL-2、IL-4、IL-6和IL-8水平的变化%Change of the Level of IL-2, IL-4, IL-6 and IL-8 of Irritability Asthma Patients

    Institute of Scientific and Technical Information of China (English)

    王爱华; 李全新

    2000-01-01

    为了观察白细胞介素在哮喘发病中的作用,该文分别对哮喘发作期20例 ,缓解期12例患者及正常对照组10例进行了血清IL-2、IL-4、IL-6和IL-8的测定,结果发现 ,发作期患者血清IL-2水平下降,而IL-4、IL-6和IL-8水平均增高,缓解期均恢复至正常水平.提示这些细胞因子在哮喘发病过程中起着重要作用.

  14. Influence of Live Combined Bifidobacterium and Lactobacillus Tablet for Intestinal Microflora and Serum IFN-γ、IL-4 in Children with Type 1 Diabetes Mellitus%双歧杆菌乳杆菌三联活菌片对1型糖尿病肠道菌群和血清 IFN-γ、IL-4的影响

    Institute of Scientific and Technical Information of China (English)

    牛文忠; 丁显春

    2016-01-01

    Objective To explore the influence of live combined bifidobacterium and lactobacillus tablet for intestinal microflora and serum IFN-γ and IL-4 in children with type 1 diabetes mellitus (T1DM). Methods 25 children with T1DM were selected as observation group from February 2014 to January 2015 in pediatrics department of Nanyang Central Hospital,and 25 healthy children undergoing physical examination at the same time period were selected as control group.All children aged from 3 to 8 years old.The observation group were treated with insulin and live combined bifidobacterium and lactobacillus tablet,0.5 g per time and three times per day for 1 month.The control group were without any treatment.The changes of intestinal microflora,serum IFN-γand IL-4 levels were compared between observation group and control group.In observation group,the changes were compared between pre-treatment and 1 month post-treatment. Results The quantity of bifidobacterium and lactobacillus in observation group was lower than the control group,the level of IFN-γ and IFN-γ/IL-4 in observation group was higher than the control group (P <0.05 );In observation group,the quantity of bifidobacterium and lactobacillus in pre-treatment was lower than post-treatment,the level of IFN-γand IFN-γ/IL-4 in pre-treatment was higher than post-treatment(all P <0.05). Conclusion Live combined bifidobacterium and lactobacillus tablet may improve the intestinal microflora and restore the balance of Th1 /Th2 in children with T1DM.%目的:观察双歧杆菌乳杆菌三联活菌片对1型糖尿病(T1DM)患儿肠道菌群及血清 IFN-γ和 IL-4的影响。方法选取25例南阳市中心医院儿科2014年2月至2015年1月 T1DM患儿为观察组,选取同时期健康体检儿童25例为对照组。入选对象年龄3~8岁。观察组给予胰岛素治疗,同时给予双歧杆菌乳杆菌三联活菌片,每次0.5 g,每日3次,口服,疗程1个月;对照组未予任何治疗措施。

  15. Production of cytokines of type II (IL-4 and IL-13) by basophil polynuclear: effects of chimiokins and stimulation by the diesel particulates; Production de cytokines de type 2 (IL-4 et IL-13) par les polynucleaires basophiles: effects des chimiokines et stimulation par les particules de diesel

    Energy Technology Data Exchange (ETDEWEB)

    Devouassoux, G.

    2000-07-01

    Cytokines of type II are critical factors in the generation of allergic inflammation. There is a correlation between the allergy incidence and the pollutants exposition. The impact of the diesel particles on the allergic response is established but their impact on the basophil is unknown. This study shows that the basophil is a target for the diesel particles, responsible of an important production of IL-4, independent of the clinical status but dependent of the oxidative stress. (A.L.B.)

  16. Graves病患者血清IL-4、IL-12、IL-13及ICAM-1、CRP、TNF-α水平变化研究%The study of the level changes on the serum IL-4,IL-12,IL-13 and ICAM-1,CRP,TNF-α in the patients with Graves disease

    Institute of Scientific and Technical Information of China (English)

    王晓书

    2010-01-01

    目的 探讨Graves病患者血清IL-4、IL-12、IL-13及ICAM-1、CRP、TNF-α水平变化规律.方法 选取2008年11月~2010年7月于笔者所在医院进行治疗的60例Graves病患者为研究对象,将其设为观察组,同时选取同期的60名健康人为对照组,对两组人员的血清IL-4、IL-12、IL-13及ICAM-1、CRP、TNF-α水平进行检测及比较.结果 经研究比较发现,观察组的血清IL-4、IL-12、IL-13及ICAM-1、CRP、TNF-α水平均明显高于对照组,同时随着疾病的加重水平也呈现增高趋势,经比较有显著性差异或有非常显著性差异(P<0.05或P<0.01).结论 Graves病患者血清IL-4、IL-12、IL-13及ICAM-1、CRP、TNF-α水平变化对于了解疾病的严重程度及发展转归均有积极的意义.

  17. 哮喘造模不同阶段的小鼠支气管肺泡灌洗液中IL-4、IL-12、IL-13的检测及意义%The significance of detected levels of BALF IL-4, IL-12 and IL-13 in the different periods of asthmatic mice model

    Institute of Scientific and Technical Information of China (English)

    程静; 梁红艳; 姜晓峰

    2013-01-01

    Objective To investigate the variation of mice BALF IL-4、IL-12 and IL-13 in different periods from sen sitized to challenged ,of asthmatic model, and further explored the immunological pathogenesis mechanism of asthma. Methods The model of asthma in mice was established by egg protein sensitizing 55BalB/C mice were randomly divid ed into eleven groups included 1 control group(N), and each group contains five mice. Four sensitized groups were named S(Ⅰ-Ⅳ)which were divided by the four phases of sensitizing and six challenged groups were named C(Ⅰ-Ⅳ) which were divided by the six phases of challenging. All sensitized and challenged groups were administered intraperito neally 0.1 ml of 0.01% OVA and 0. lml of 20% AI(OH)3. The four phases of sensitized was divided into four groups, the sensitized group Ⅰ was injected twice and the group Ⅱ third, group Ⅲ fourth and group Ⅳ was injected fifth. Then the challenged groups were continue accepted with 5%OVA aerosol inhaling after being sensitized. OVA aerosol inhaling was lasting 27 days, the six phases of challenged was selected the 7 d,ll d,15 d,19 d,23 d and 27 d respec tively. The normal control group was injected and inhalated saline instead of OVA. The levels of BALF IL-4, IL-12 and IL-13 of each group were measured by ELISA kit. Results The BALF IL-4 and IL-13 levels of challenged mice were higher than that of sensitized, however the IL-12 level of challenged mice was lower than the sensitized mice. We also found that the IL-4 and IL-13 levels were gradually raised along with the increased frequency of OVA inhalation, while the IL-12 level decreased. For the stimulated group,the IL-12 level was significantly degraded from SI group, while the IL-4 and IL-13 levels were significantly elevated from SII group. IL-4 and IL-13 showed a significantly positive correla tion (r=0. 968), IL-12 and IL-4 were negative correlated (r=-0. 771), IL-12 and IL-13 were significantly negative correlated(r= -0. 856

  18. Mercury in Hair Is Inversely Related to Disease Associated Damage in Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    William Crowe

    2015-12-01

    Full Text Available Systemic lupus erythematosus (SLE is an autoimmune inflammatory disease, and environmental factors are proposed to exacerbate existing symptoms. One such environmental factor is mercury. The aim of this study was to investigate the relationship between exposure to mercury (Hg and disease activity and disease associated damage in Total Hg concentrations in hair and urine were measured in 52 SLE patients. Dental amalgams were quantified. Disease activity was assessed using three indexes including the British Isles Lupus Assessment Group Index (BILAG. Disease associated damage was measured using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology SLICC/ACR Damage Index. Pearson’s correlation identified a significant negative correlation between hair Hg and BILAG (r = −0.323, p = 0.029 and SLICC/ACR (r = −0.377, p = 0.038. Multiple regression analysis identified hair Hg as a significant predictor of disease associated damage as determined by SLICC/ACR (β = −0.366, 95% confidence interval (CI: −1.769, −0.155 p = 0.019. Urinary Hg was not related to disease activity or damage. Fish consumption is the primary route of MeHg exposure in humans and the inverse association of hair Hg with disease activity observed here might be explained by the anti-inflammatory effects of n-3 long chain polyunsaturated fatty acids also found in fish.

  19. Mercury in Hair Is Inversely Related to Disease Associated Damage in Systemic Lupus Erythematosus.

    Science.gov (United States)

    Crowe, William; Doherty, Leanne; Watson, Gene; Armstrong, David; Ball, Elisabeth; Magee, Pamela; Allsopp, Philip; Bell, Aubrey; Strain, J J; McSorley, Emeir

    2015-12-23

    Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease, and environmental factors are proposed to exacerbate existing symptoms. One such environmental factor is mercury. The aim of this study was to investigate the relationship between exposure to mercury (Hg) and disease activity and disease associated damage in Total Hg concentrations in hair and urine were measured in 52 SLE patients. Dental amalgams were quantified. Disease activity was assessed using three indexes including the British Isles Lupus Assessment Group Index (BILAG). Disease associated damage was measured using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology SLICC/ACR Damage Index. Pearson's correlation identified a significant negative correlation between hair Hg and BILAG (r = -0.323, p = 0.029) and SLICC/ACR (r = -0.377, p = 0.038). Multiple regression analysis identified hair Hg as a significant predictor of disease associated damage as determined by SLICC/ACR (β = -0.366, 95% confidence interval (CI): -1.769, -0.155 p = 0.019). Urinary Hg was not related to disease activity or damage. Fish consumption is the primary route of MeHg exposure in humans and the inverse association of hair Hg with disease activity observed here might be explained by the anti-inflammatory effects of n-3 long chain polyunsaturated fatty acids also found in fish.

  20. Isolated Endobronchial Mycobacterium avium Disease Associated with Lobar Atelectasis in an Immunocompetent Young Adult: A Case Report and Literature Review.

    Science.gov (United States)

    Kim, Hye In; Kim, Ji Won; Kim, Jun Young; Kim, Young Nam; Kim, Jin Hae; Jeong, Byeong-Ho; Chung, Myung Jin; Koh, Won-Jung

    2015-10-01

    The prevalence of lung diseases caused by nontuberculous mycobacteria (NTM) is increasing worldwide. Unlike pulmonary tuberculosis, endobronchial NTM diseases are very rare with the majority of cases reported in patients with human immunodeficiency virus infection and acquired immune deficiency syndrome. We reported a rare case of endobronchial Mycobacterium avium disease associated with lobar atelectasis in a young immunocompetent patient and reviewed the relevant iterature.

  1. Respuesta de IFN-y e Il-4 en ratones inoculados con una proteína G recombinante del virus de la rabia

    Directory of Open Access Journals (Sweden)

    Edith Rojas-Anaya

    2015-01-01

    Full Text Available El objetivo de este estudio fue comparar el comportamiento de IFN-  e IL-4 en ratones inoculados con proteína G recombinante del virus de la rabia, que se expresa en maíz transgénico o baculovirus. Para este pr opósito, grupos de ratones se inocularon de la siguiente manera: Grupo 1, vacuna contra el virus de la rabia inactivado vía im; Grupo 2, proteína G recombinante deri vada de plantas por vía oral; Grupo 3, proteína G expresada en baculovirus vía im; Grupo 4, proteína G expresada en baculovirus por vía oral; Grupo 5, maíz no tran sformado por vía oral. Los niveles de IFN-  e IL-4 y los anticuerpos específicos se evaluaron cada 15 días. El desafío se realizó a los 60 días post inoculación (pi. Los grupos 1 y 3 promovieron un a mejor respuesta humoral. Por otro lado, los resultados demostraron que los mismos grupos mostraron los mejores niveles de IFN -  en el día 10 pi; mientras que la IL-4 se detectó en el día 15 pi. Para el estudio de supervivencia, el 83 % de los ratones inmunizados con vacuna inactivada, maíz y los inoculados im con extractos de baculovirus sob revivieron la infección viral. La proteína G de la rabia recombinante expresada en baculovirus promovió IFN-  y los anticuerpos de una manera similar a la vacuna de rabia inactivada. A pesar de esto los ratones alime ntados con maíz transgénico sobrevivieron al desafío en el mismo porcentaje que el grupo 3.

  2. Inferring drug-disease associations based on known protein complexes.

    Science.gov (United States)

    Yu, Liang; Huang, Jianbin; Ma, Zhixin; Zhang, Jing; Zou, Yapeng; Gao, Lin

    2015-01-01

    Inferring drug-disease associations is critical in unveiling disease mechanisms, as well as discovering novel functions of available drugs, or drug repositioning. Previous work is primarily based on drug-gene-disease relationship, which throws away many important information since genes execute their functions through interacting others. To overcome this issue, we propose a novel methodology that discover the drug-disease association based on protein complexes. Firstly, the integrated heterogeneous network consisting of drugs, protein complexes, and disease are constructed, where we assign weights to the drug-disease association by using probability. Then, from the tripartite network, we get the indirect weighted relationships between drugs and diseases. The larger the weight, the higher the reliability of the correlation. We apply our method to mental disorders and hypertension, and validate the result by using comparative toxicogenomics database. Our ranked results can be directly reinforced by existing biomedical literature, suggesting that our proposed method obtains higher specificity and sensitivity. The proposed method offers new insight into drug-disease discovery. Our method is publicly available at http://1.complexdrug.sinaapp.com/Drug_Complex_Disease/Data_Download.html.

  3. The functional importance of disease-associated mutation

    Directory of Open Access Journals (Sweden)

    Klein Teri E

    2002-09-01

    Full Text Available Abstract Background For many years, scientists believed that point mutations in genes are the genetic switches for somatic and inherited diseases such as cystic fibrosis, phenylketonuria and cancer. Some of these mutations likely alter a protein's function in a manner that is deleterious, and they should occur in functionally important regions of the protein products of genes. Here we show that disease-associated mutations occur in regions of genes that are conserved, and can identify likely disease-causing mutations. Results To show this, we have determined conservation patterns for 6185 non-synonymous and heritable disease-associated mutations in 231 genes. We define a parameter, the conservation ratio, as the ratio of average negative entropy of analyzable positions with reported mutations to that of every analyzable position in the gene sequence. We found that 84.0% of the 231 genes have conservation ratios less than one. 139 genes had eleven or more analyzable mutations and 88.0% of those had conservation ratios less than one. Conclusions These results indicate that phylogenetic information is a powerful tool for the study of disease-associated mutations. Our alignments and analysis has been made available as part of the database at http://cancer.stanford.edu/mut-paper/. Within this dataset, each position is annotated with the analysis, so the most likely disease-causing mutations can be identified.

  4. Effect of glycyrrhizin on chronic urticaria patients in IL-4,IL-8,IL-17 and IL-22%18-β甘草酸苷对慢性荨麻疹患者血清中IL-4、IL-8、IL-17和IL-22的影响

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    目的:通过对18-β甘草酸苷治疗前后慢性荨麻疹患者血清中IL-4、IL-8、IL-17和IL-22的检测,探讨甘草酸苷治疗慢性荨麻疹的作用机制。方法:用Western blot检测法分别检测20例慢性荨麻疹患者经甘草酸苷治疗前、后及20例健康对照组血清中IL-4、IL-8、IL-17和IL-22的水平。结果:慢性荨麻疹患者经18-β甘草酸苷治疗前血清中IL-4浓度(22.75±6.87pg/ml)、IL-8浓度(20.26±4.52pg/ml)、IL-17浓度(24.62±7.28pg/ml)和IL-22浓度(23.26±9.04pg/ml)高于健康对照组(P<0.05)。治疗后,IL-4浓度(14.44±4.29pg/ml)、IL-8浓度(12.24±3.32pg/ml)、IL-17浓度(13.32±1.61pg/ml)和IL-22浓度(14.32±1.59pg/ml)较治疗前显著降低(P<0.05),与健康对照比较差异无统计学意义(P>0.05)。结论:慢性荨麻疹患者的血清中存在IL-4、IL-8、IL-17和IL-22水平异于正常,提示慢性荨麻疹患者的机体免疫功能紊乱;而18-β甘草酸苷治疗后血清中IL-4、IL-8、IL-17和IL-22明显降低,提示18-β甘草酸苷可能通过影响辅助T细胞相关因子来发挥治疗慢性荨麻疹的作用。%Objective Based on measurement of chronic urticaria patients serum IL-4 and IL-8,IL-17 and IL-22 before and after 18 beta glycyrrhizin in the treatment of glycyrrhizin mechanism on treating chronic urticaria. Methods The levels of serum IL-22,IL-8,IL-17 and IL-4 in 20 cases of chronic urticaria were detected by blot Western assay and 20 cases of healthy controls. Results In patients with chronic urticaria by 18 beta glycyrrhizin treatment IL and serum concentrations of IL- 4(22.75 ± 6.87pg/ml),IL- 8 concentration(20.26 ± 4.52pg/ml),IL- 17 concentration(24.62 ± 7.28pg/ml)and IL- 22 concentration (23.26±9.04pg/ml),higher than the healthy control group(P0.05). Conclusion The serum of patients with chronic urticaria of IL-4 and IL-8,IL-17 and IL-22 levels different from normal,suggesting that chronic urticaria patients with the

  5. 感染性喉炎和痉挛性喉炎患儿血清中IL-4、IFN-γ和IgE水平检测的临床意义%Clinical significance of IL-4,IFN-γand IgE in children with acute infectious laryngitis and in children with spasmodic laryngitis

    Institute of Scientific and Technical Information of China (English)

    薛国昌; 任明星; 周静月; 沈琳娜; 宋月娟; 夏欢; 曹丽

    2014-01-01

    目的:探讨感染性喉炎和痉挛性喉炎患儿血清中IL-4、IFN-γ和IgE水平的变化及临床意义。方法采用ELISA双抗体夹心法检测26例感染性喉炎、31例痉挛性喉炎患儿入院时(急性期)、出院前(恢复期)及正常对照组儿童(25名)血清IL-4、IFN-γ水平;采用荧光酶联免疫法检测IgE水平,并进行比较。结果急性期感染性喉炎和痉挛性喉炎患儿血清IL-4、IgE水平明显高于对照组(P均"0.05);急性期感染性喉炎患儿血清IgE水平明显低于痉挛性喉炎患儿(P"0.05);恢复期感染性喉炎和痉挛性喉炎患儿血清IL-4、IgE水平较急性期明显降低(P均"0.05),恢复期感染性喉炎患儿血清IgE水平明显低于痉挛性喉炎患儿(P"0.05)。急性期感染性喉炎和痉挛性喉炎患儿血清IFN-γ水平明显低于对照组(P均"0.05);恢复期感染性喉炎和痉挛性喉炎患儿血清IFN-γ水平较急性期明显升高(P均"0.05)。结论感染性喉炎和痉挛性喉炎患儿存在免疫功能紊乱,IL-4、IFN-γ和IgE在患儿免疫病理机制中起重要作用,检测IgE水平有助于两种喉炎的鉴别。%Objective To investigate clinical significance and the change of serum IL-4,IFN-γand IgE levels and their clinical significance in children with acute infectious laryngitis and in children with spas-modic laryngitis. Methods Serum samples were obtained from 26 children with acute infectious laryngitis, 31 children with spasmodic laryngitis and 25 healthy children. The change of serum IL-4,IFN-γand IgE levels were observed detected by ELISA in serum when hospital admission (acute stage)were observed.Aand before discharge (convalescent stage). ELISA was used to determine the levels of serum IL-4,IFN-γin serum. Serum IgE level was determined with enzyme-linked fluoroimmuneassay. Results The levels of IL-4 and IgE in chil-dren with acute infectious laryngitis and in children with spasmodic

  6. 亚洲牛带绦虫感染家猪后血清IL-4和IL-10含量检测

    Institute of Scientific and Technical Information of China (English)

    杨鹏; 党荣敏; 谢洪书; 刘元忠

    2010-01-01

    @@ 亚洲牛带绦虫(Taenia Saginata asiatica)是近30年来发现的一种新的人体带绦虫.但亚洲牛带绦虫的研究仅局限于从形态学、生物学等方面与传统牛带绦虫进行比较[1-3],有关宿主抗亚洲牛带绦虫感染的研究报道较少.本研究动态观察感染亚洲牛带绦虫的家猪血清白细胞介素-4(IL-4)和白细胞介素-10(IL-10)含量变化,初步讨论家猪抗亚洲牛带绦虫感染免疫应答机制.现将结果报告如下.

  7. FREQUENCY DISTRIBUTION OF INTRONIC POLYMORPHISMS OF IL1-raVNTR AND IL-4VNTR IN RHEUMATIC MITRAL VALVE DISEASE IN CAUCASIAN POPULATION OF SIBERIA

    Directory of Open Access Journals (Sweden)

    A. V. Ponasenko

    2015-01-01

    Full Text Available A search for associations between allelic variations of immune response genes, and mitral stenosis associated with rheumatic heart disease, represents an important task when studying the pathogenesis of cardiovascular disorders among inhabitants of large industrial regions in Western Siberia. Among multiple polymorphisms of interleukin-encoding genes, a particular attention should be paid to association studies of some intronic polymorphisms with variable numbers of tandem repeats (VNTR. In this respect, genotyping of interleukin 1 receptor antagonist genes (IL-1ra86bp VNTR and interleukin 4 (IL-470bp VNTR has shown positive associations between the intron 2 IL-1ra*3R/3R microsatellite polymorphism, intron 3 IL-4*2R/2R variant, and the risk of mitral stenosis development in patients with rheumatic heart disease (OR = 12.71; p = 0.0001.  

  8. Taurine supplementation regulates Iκ-Bα protein expression in adipose tissue and serum IL-4 and TNF-α concentrations in MSG obesity.

    Science.gov (United States)

    Caetano, Luiz Carlos; Bonfleur, Maria Lúcia; Ribeiro, Rosane Aparecida; Nardelli, Tarlliza Romanna; Lubaczeuski, Camila; do Nascimento da Silva, Juliana; Carneiro, Everardo Magalhães; Balbo, Sandra Lucinei

    2017-03-01

    Obesity is usually associated with low-grade inflammation, which impairs insulin action. The amino acid, taurine (TAU), regulates glucose homeostasis and lipid metabolism and presents anti-inflammatory actions. Here, we evaluated whether inflammatory markers are altered in the serum and retroperitoneal adipose tissue of monosodium glutamate (MSG) obese rats, supplemented or not with TAU. Male Wistar rats received subcutaneous injections of MSG (4 mg/kg body weight/day, MSG group) or hypertonic saline (CTL) during the first 5 days of life. From 21 to 120 days of age, half of each of the MSG and CTL groups received 2.5 % TAU in their drinking water (CTAU and MTAU). At 120 days of age, MSG rats were obese and hyperinsulinemic. TAU supplementation reduced fat deposition without affecting insulinemia in MTAU rats. MSG rats presented increased pIκ-Bα/Iκ-Bα protein expression in the retroperitoneal adipose tissue. TAU supplementation decreased the ratio of pIκ-Bα/Iκ-Bα protein, possibly contributing to the increased Iκ-Bα content in MTAU adipose tissue. Furthermore, MSG obesity or supplementation did not alter TNF-α, IL-1β or IL-6 content in adipose tissue. In contrast, MSG rats presented lower serum TNF-α, IL-4 and IL-10 concentrations, and these alterations were prevented by TAU treatment. MSG obesity in rats was not associated with alterations in pro-inflammatory markers in retroperitoneal fat stores; however, reductions in the serum concentrations of anti-inflammatory cytokines and of TNF-α were observed. TAU treatment decreased adiposity, and this effect was associated with the normalization of circulating TNF-α and IL-4 concentrations in MTAU rats.

  9. PAR-2, IL-4R, TGF-β and TNF-α in bronchoalveolar lavage distinguishes extrinsic allergic alveolitis from sarcoidosis.

    Science.gov (United States)

    Matěj, Radoslav; Smětáková, Magdalena; Vašáková, Martina; Nováková, Jana; Sterclová, Martina; Kukal, Jaromír; Olejár, Tomáš

    2014-08-01

    Sarcoidosis (SARC) and extrinsic allergic alveolitis (EAA) share certain markers, making a differential diagnosis difficult even with histopathological investigation. In lung tissue, proteinase-activated receptor-2 (PAR-2) is primarily investigated with regard to epithelial and inflammatory perspectives. Varying levels of certain chemokines can be a useful tool for distinguishing EAA and SARC. Thus, in the present study, differences in the levels of transforming growth factor (TGF)-β1, tumor necrosis factor (TNF)-α, interleukin-4 receptor (IL-4R) and PAR-2 in bronchoalveolar lavage fluid (BALF) were compared, using an ELISA method, between 14 patients with EAA and six patients with SARC. Statistically significant higher levels of IL-4R, PAR-2 and the PAR-2/TGF-β1 and PAR-2/TNF-α ratios were observed in EAA patients as compared with SARC patients. Furthermore, the ratios of TNF-α/total protein, TGF-β1/PAR-2 and TNF-α/PAR-2 were significantly lower in EAA patients than in SARC patients. The results indicated a higher detection of PAR-2 in EAA samples in association with TNF-α and TGF-β levels. As EAA and PAR-2 in parallel belong to the Th2-mediated pathway, the results significantly indicated an association between this receptor and etiology. In addition, the results indicated that SARC is predominantly a granulomatous inflammatory disease, thus, higher levels of TNF-α are observed. Therefore, the detection of PAR-2 and investigated chemokines in BALF may serve as a useful tool in the differential diagnosis between EAA and SARC.

  10. Impaired SLAM-SLAM homotypic interaction between invariant NKT cells and dendritic cells affects differentiation of IL-4/IL-10-secreting NKT2 cells in nonobese diabetic mice.

    Science.gov (United States)

    Baev, Denis V; Caielli, Simone; Ronchi, Francesca; Coccia, Margherita; Facciotti, Federica; Nichols, Kim E; Falcone, Marika

    2008-07-15

    The regulatory function of invariant NKT (iNKT) cells for tolerance induction and prevention of autoimmunity is linked to a specific cytokine profile that comprises the secretion of type 2 cytokines like IL-4 and IL-10 (NKT2 cytokine profile). The mechanism responsible for iNKT cell differentiation toward a type 2 phenotype is unknown. Herein we show that costimulatory signals provided by the surface receptor signaling lymphocytic activation molecule (SLAM) on myeloid dendritic cells (mDC) to iNKT cells is crucial for NKT2 orientation. Additionally, we demonstrate that the impaired acquisition of an NKT2 cytokine phenotype in nonobese diabetic (NOD) mice that spontaneously develop autoimmune diabetes is due to defective SLAM-induced signals generated by NOD mDC. Mature mDC of C57BL/6 mice express SLAM and induce C57BL/6 or NOD iNKT cells to acquire a predominant NKT2 cytokine phenotype in response to antigenic stimulation with the iNKT cell-specific Ag, the alpha-galactosylceramide. In contrast, mature NOD mDC express significantly lower levels of SLAM and are unable to promote GATA-3 (the SLAM-induced intracellular signal) up-regulation and IL-4/IL-10 production in iNKT cells from NOD or C57BL/6 mice. NOD mice carry a genetic defect of the Slamf1 gene that is associated with reduced SLAM expression on double-positive thymocytes and altered iNKT cell development in the thymus. Our data suggest that the genetic Slamf1 defect in NOD mice also affects SLAM expression on other immune cells such as the mDC, thus critically impairing the peripheral differentiation of iNKT cells toward a regulatory NKT2 type.

  11. 旋毛虫感染对过敏性哮喘小鼠血清总IgE、IL-4、IL-5的影响%Experimental study on changes of serum total IgE, IL-4 and IL-5 in mice with Trichinella spiralis induced allergic asthma

    Institute of Scientific and Technical Information of China (English)

    马萍; 闫玉文; 包春雨

    2013-01-01

    目的 研究旋毛虫感染对过敏性哮喘小鼠血清TIgE、IL-4、IL-5的影响.方法 随机将20只BALA/c雌性小鼠分为4组,每组5只,Ⅰ组为空白对照组,Ⅱ组为单纯过敏性哮喘组,Ⅲ组为感染旋毛虫后哮喘组,Ⅳ组为单纯感染旋毛虫组.首先,将200~300条旋毛虫囊包幼虫经口感染Ⅲ、Ⅳ组小鼠,建立旋毛虫感染模型.28 d后,用卵清白蛋白分别对Ⅱ组和Ⅲ组小鼠进行致敏激发,建立过敏性哮喘模型.56 d后,取小鼠血清,用ELISA法检测TIgE、IL-4、IL-5水平.结果 4组小鼠总IgE水平分别为:(61.79±25.79)ng/ml、(437.08±75.68)ng/ml、(251.64±107.27)ng/ml和(446.12±74.32)ng/ml;IL-4水平分别为:(136.49±31.17)pg/L、(209.80±21.57)pg/L、(162.79±17.69)pg/L和(182.71±12.08)pg/L;IL-5水平分别为:(7.31±1.86)ng/L、(16.00±2.28)ng/L、(9.24±1.73)ng/L和(11.41±2.11)ng/L;与Ⅱ组相比较,Ⅲ组血清中总IgE、IL-4及IL-5水平明显降低(P<0.05).结论 旋毛虫感染可以抑制过敏性哮喘小鼠血清TIgE、IL-4及IL-5的表达.%Objective To study the effect of Trichinella spiralis infection on total IgE, IL - 4 and IL - 5 in serum of the mice with allergic asthma. Methods Twenty female BALB/c mice were randomly divided into four groups of five mice each, including Ⅰ as control group, Ⅱ as allergic asthma group, Ⅲ as asthma followed by Trichinella spiralis infection, Ⅳ as Trichinella spiralis infected group. Firstly, the animals in group Ⅲ and Ⅳ were infected with 200 -300 Trichinella spiralis muscle larvae. Twenty - eight days later , ovalbumin ( OVA) was used to induce the allergic asthma for mice in group Ⅱ and Ⅲ , in order to establish asthma animal model. After 56 days, all mice were sacrificed, levels of TIgE, IL - 4 and IL - 5 in serum were measured by ELISA. Results The TIgE levels in group Ⅰ , Ⅱ , Ⅲ and Ⅳ were (61.79 ±25.79) ng/ml, (437.08 ±75.68) ng/ml, (251.64 ±107.27) ng/ml and (446. 12 ± 74.32)ng/ml, respectively. The

  12. PBMDA: A novel and effective path-based computational model for miRNA-disease association prediction.

    Directory of Open Access Journals (Sweden)

    Zhu-Hong You

    2017-03-01

    Full Text Available In the recent few years, an increasing number of studies have shown that microRNAs (miRNAs play critical roles in many fundamental and important biological processes. As one of pathogenetic factors, the molecular mechanisms underlying human complex diseases still have not been completely understood from the perspective of miRNA. Predicting potential miRNA-disease associations makes important contributions to understanding the pathogenesis of diseases, developing new drugs, and formulating individualized diagnosis and treatment for diverse human complex diseases. Instead of only depending on expensive and time-consuming biological experiments, computational prediction models are effective by predicting potential miRNA-disease associations, prioritizing candidate miRNAs for the investigated diseases, and selecting those miRNAs with higher association probabilities for further experimental validation. In this study, Path-Based MiRNA-Disease Association (PBMDA prediction model was proposed by integrating known human miRNA-disease associations, miRNA functional similarity, disease semantic similarity, and Gaussian interaction profile kernel similarity for miRNAs and diseases. This model constructed a heterogeneous graph consisting of three interlinked sub-graphs and further adopted depth-first search algorithm to infer potential miRNA-disease associations. As a result, PBMDA achieved reliable performance in the frameworks of both local and global LOOCV (AUCs of 0.8341 and 0.9169, respectively and 5-fold cross validation (average AUC of 0.9172. In the cases studies of three important human diseases, 88% (Esophageal Neoplasms, 88% (Kidney Neoplasms and 90% (Colon Neoplasms of top-50 predicted miRNAs have been manually confirmed by previous experimental reports from literatures. Through the comparison performance between PBMDA and other previous models in case studies, the reliable performance also demonstrates that PBMDA could serve as a powerful

  13. Granulomatous disease associated with pulmonary deposition of titanium.

    Science.gov (United States)

    Redline, S; Barna, B P; Tomashefski, J F; Abraham, J L

    1986-10-01

    A patient presented with granulomatous lung disease associated with the pulmonary deposition of various metallic particles. To evaluate the relation between the metallic dust and the granulomatous process, lymphocyte transformation tests to aluminium sulphate, titanium chloride, beryllium sulphate, and nickel sulphate were performed. A lymphocyte proliferative response to titanium chloride was observed on two separate occasions; no responses to the other metals were shown. These results are consistent with hypersensitivity to titanium, and suggest, in this individual, a possible aetiological role between the inhalation of titanium and a granulomatous disease process.

  14. Graves' disease associated with alopecia areata developing after Hashimoto's thyroiditis.

    Science.gov (United States)

    Aşık, Mehmet; Binnetoğlu, Emine; Şen, Hacer; Tekeli, Zeliha; Uysal, Fatma; Ukinç, Kubilay

    2013-01-01

    Graves' disease and Hashimoto's thyroiditis are the most common autoimmune thyroid diseases. Hypothyroidism can develop in patients with Graves' disease, either spontaneously or as a result of radioactive iodine therapy or surgery. However, it is rare for patients with Hashimoto's thyroiditis to subsequently develop Graves' disease. We report a case of alopecia areata associated with Graves' disease in a 41-year-old woman who had previously been diagnosed with Hashimoto's disease. Alopecia areata is an autoimmune disease associated with other autoimmune diseases such as thyroid disorders, anemia, and other skin disorders.

  15. Madelung's disease associated with polyneuropathy and symptomatic hypokalemia

    Directory of Open Access Journals (Sweden)

    Hoi-Fong Chan

    2013-05-01

    Full Text Available Madelung's disease (multiple symmetric lipomatosis is a rare disease characterized by abnormal diffuse lipomatosis in proximal upper limbs and neck. Previous reports have shown that this disease is associated with alcoholism, polyneuropathy, mitochondrial disease, and glucose intolerance. Here, we describe a 46-year-old man having Madelung's disease associated with polyneuropathy and symptomatic hypokalemia. He presented with insidious-onset weakness and numbness in lower limbs for 7 years and recent deterioration of symptoms. Proximal weakness improved with potassium supplement. Our observation may extend the phenotype of Madelung's disease to hypokalemic periodic paralysis.

  16. IL-4对小鼠骨髓树突状细胞表面分子CD11c、CD80、CD86表达的影响及其意义%Influence and significance of IL-4 on the expression of CD11c,CD80,CD86 on mouse bone marrow ;DC cells

    Institute of Scientific and Technical Information of China (English)

    田晋生; 邓勇志

    2014-01-01

    Objective To explore the efficacy of IL-4 on the expression of phenotype of CD11c, CD80, CD86 and its underlying meaning in cultured dendritic cells (DC). Methods On the base of the routine culture, both the control group (n=5, 30 holes) and the test group (n=5, 30 holes) of mouse bone marrow cells were added with 20 ng/ml GM-CSF. In addition the test group was further treated with 20 ng/ml of IL-4. After 7 days, both groups were observed under microscope and CD11c, CD80, CD86 were measured with flow cytometry. Results At the 7 days, the DC cells were found under microcopy in the test group but not in the control group. Flow cytometry demonstrated the cell phenotype of CD11c (0.546 ±0.289), CD80(0.506±0.085) and CD86(0.562±0.260) expression in test group were higher than that of the control group, which were CD11c (0.236±0.058), CD80 (0.279±0.096) and CD86 (0.237±0.070), respectively (P<0.05). Conclusions IL-4 could effectively promote the phenotype molecule expression of CD11c,CD80,CD86, and thus stimulate the differentiation and maturation of bone marrow cells to DC cells.%目的:探讨IL-4对小鼠骨髓树突状细胞(DC细胞)表面分子CD11c、CD80、CD86表达的影响及其意义。方法对照组(n=5只,30孔)应用20 ng/ml GM-CSF,实验组(n=5只,30孔)应用20 ng/ml GM-CSF+20 ng/ml IL-4分别刺激小鼠骨髓细胞生长,隔日进行细胞换液,观察并对比细胞形态学变化,流式细胞仪测定 DC 细胞表面相关分子表达。结果实验组诱导小鼠骨髓细胞第7日观察可见DC细胞形态,对照组第7日未发现明显DC细胞形态,流式细胞仪测定实验组 CD11c(0.546±0.289)、CD80(0.506±0.085)、CD86(0.562±0.260)表达分别较对照组CD11c(0.236±0.058)、CD80(0.279±0.096)、CD86(0.237±0.070)表达明显增高(P<0.05)。结论 IL-4可以促进小鼠骨髓DC细胞表面分子CD11c、CD80、CD86表达,促进DC细胞分化成熟。

  17. Effects of five foods on the inflammatory reaction and IL-4, IL-17 in mice model of CACD%5种食物对小鼠接触性炎症反应及血清 IL-4和 IL-17的影响

    Institute of Scientific and Technical Information of China (English)

    李婷; 胡阳; 陈向明; 张海清; 俞爱华; 王国江

    2014-01-01

    Objective: To determine the effects of mushroom, chillies, ribbonfish, mutton and sea shrimp on contact dermatitis in mice model. Methods: The contact dermatitis model was constructed by DNFB. The mice were divided into 5 groups and fed with the soup of 5 foods by gavage and the mice in control group were fed with water. Ear thickness and weight were measured. The levels of IL-4 and IL-17 in serum were detected by ELISA. Results: Compared with control group, the ear thickness and weight, and the levels of IL-17 were increased in the chillies group and mutton group(P0.05). Conclusion: Chillies and mutton may aggravate the inflamma-tory reaction in contact dermatitis by upregulating IL-17 expression.%目的::明确香菇、辣椒、带鱼、羊肉和海虾5种食物对慢性变应性接触性皮炎(CACD)小鼠模型炎症反应及血清 IL-4和 IL-17表达的影响。方法:36只小鼠用2,4-二硝基氟苯诱导建立CACD 模型,5种食物煎煮后灌胃,对照组予纯水灌胃。测量每组耳厚度和耳重量并用 ELISA 检测血清 IL-4和 IL-17水平。结果:与对照组相比,辣椒和羊肉明显增加耳厚度、耳重量和血清 IL-17水平(P0.05),但显著下调血清 IL-4水平(P0.05)。结论:辣椒和羊肉可能通过上调血清 IL-17水平加重CACD 小鼠模型炎症反应。

  18. 小檗碱对LPS、 IL-4诱导的小鼠RAW264.7细胞分泌TNF-α、 IL-10的影响%Effects of Berberine on TNF-α and IL-10 Secretion Induced by LPS and IL-4 in RAW264.7 Cells

    Institute of Scientific and Technical Information of China (English)

    吴阳阳; 董燕; 易浪; 王青

    2014-01-01

    目的:观察小檗碱(Berberine, Ber)对脂多糖(LPS)以及白介素-4(IL-4)诱导的RAW264.7细胞株分泌炎症因子中肿瘤坏死因子-α(TNF-α)、抑炎因子白介素(IL-10)的影响,初步探讨Ber对巨噬细胞极化的影响。方法噻唑蓝(MTT)法测定小檗碱对RAW264.7细胞增殖的影响,选取半数抑制浓度(IC50)以下的小檗碱浓度作为干预剂量;酶联免疫法(ELISA)检测小檗碱对LPS以及IL-4不同诱导状态下RAW264.7细胞分泌TNF-α、 IL-10的影响。结果小檗碱对 RAW264.7细胞的 IC50在400~800μmol·L-1之间。 LPS 作用下RAW264.7细胞促炎因子TNF-α分泌量明显升高, Ber(剂量分别为5,10,20μmol·L-1)有显著的抑制作用,并有剂量依赖关系(均P<0.01);而LPS刺激下细胞IL-10分泌量也明显升高(P<0.05),而Ber仅在20μmol·L-1剂量下表现抑制作用。在IL-4作用下, RAW264.7细胞抗炎因子IL-10分泌量明显升高, Ber (剂量分别为5,10,20μmol·L-1)有显著的抑制作用,并呈现剂量依赖关系(均P<0.01); IL-4作用下TNF-α分泌量明显降低(P<0.05), Ber对TNF-α分泌量的影响无剂量依赖性。结论 Ber对LPS刺激下促炎因子TNF-α的分泌具有抑制作用,对IL-4诱导下IL-10分泌量的升高也有抑制作用,提示Ber在巨噬细胞极化过程中有调节作用。%Objective To observe the effects of berberine on inflammatory cytokine tumor necrosis factor alpha (TNF-α) and anti-inflammatory cytokine interleukin-10(IL-10) secreted by macrophage RAW264.7 cells after stimulated by lipopolysaccharide(LPS) and IL-4 respectively, and to discuss preliminarily the effect of berberine on macrophage polarization. Methods The effect of berberine at the concentration under IC50 on RAW264.7 cells proliferation was detected by MTT assay. Macrophage RAW 264.7 cells were stimulated by LPS and IL-4 respectively, and then the secretion of TNF

  19. 甘露聚糖肽对结核性胸膜炎患者胸水中INF-γ、IL-4表达的影响%Effect of Mannatide on expression of INF-γ, IL-4 in pleural fluid of tuberculous pleurisy patients

    Institute of Scientific and Technical Information of China (English)

    贾民勇; 许志强; 山小薪; 傅玉琼; 湛晓勤

    2012-01-01

    目的 观察甘露聚糖肽对结核性胸膜炎患者的临床疗效.方法 68例入选患者随机分为观察组和对照组,采用单盲法对比研究.观察组采用甘露聚糖肽2 ml(5 mg)每日注射+常规治疗方法,对照组采用生理盐水2 ml每日注射+常规治疗方法,对比不同治疗阶段患者胸穿后取胸水使用ELISA法检测γ干扰素(INF-γ)、白介素4(IL-4)表达情况.结果 观察组治疗5d、10 d后胸水INF-γ表达高于对照组(P<0.05),而IL-4表达低于对照组(P<0.05).结论 甘露聚糖肽对结核性胸膜炎患者胸水中的免疫细胞有明显的免疫调节作用,能有较好的辅助治疗效果.%Objective To investigate the clinical effect of Mannatide injection in Tuberculous pleuritis patients.Methods 68 patients were randomly divided into treatment group and control group.To study with single-blinded study of the control method.Inject 2 ml(5 mg) of Mannatide injection to treatment groups one time each day,and at the same time give them the conventional treatment,inject 2 ml of normal saline to control groups with taking conventional treatment,observe the expression of INF-γ,IL-4 by ELISA dyeing method in hydrothorax of different patients in different therapy phase.Results 5 days and 10 days after treatment,the expression of INF-γ in hydrothorax of treatment groups is higher than the control groups (P <0.05),meanwhile,the expression of IL-4 in hydrothorax of the reatment groups is less than the control groups.Conclusions Mannatide injection have the immune adjustment function to immune cell in hydrothorax of Tuberculous pleuritis patients,and have the better Medicinal cure effect.

  20. Concerted activity of IgG1 antibodies and IL-4/IL-25-dependent effector cells trap helminth larvae in the tissues following vaccination with defined secreted antigens, providing sterile immunity to challenge infection.

    Directory of Open Access Journals (Sweden)

    James P Hewitson

    2015-03-01

    Full Text Available Over 25% of the world's population are infected with helminth parasites, the majority of which colonise the gastrointestinal tract. However, no vaccine is yet available for human use, and mechanisms of protective immunity remain unclear. In the mouse model of Heligmosomoides polygyrus infection, vaccination with excretory-secretory (HES antigens from adult parasites elicits sterilising immunity. Notably, three purified HES antigens (VAL-1, -2 and -3 are sufficient for effective vaccination. Protection is fully dependent upon specific IgG1 antibodies, but passive transfer confers only partial immunity to infection, indicating that cellular components are also required. Moreover, immune mice show greater cellular infiltration associated with trapping of larvae in the gut wall prior to their maturation. Intra-vital imaging of infected intestinal tissue revealed a four-fold increase in extravasation by LysM+GFP+ myeloid cells in vaccinated mice, and the massing of these cells around immature larvae. Mice deficient in FcRγ chain or C3 complement component remain fully immune, suggesting that in the presence of antibodies that directly neutralise parasite molecules, the myeloid compartment may attack larvae more quickly and effectively. Immunity to challenge infection was compromised in IL-4Rα- and IL-25-deficient mice, despite levels of specific antibody comparable to immune wild-type controls, while deficiencies in basophils, eosinophils or mast cells or CCR2-dependent inflammatory monocytes did not diminish immunity. Finally, we identify a suite of previously uncharacterised heat-labile vaccine antigens with homologs in human and veterinary parasites that together promote full immunity. Taken together, these data indicate that vaccine-induced immunity to intestinal helminths involves IgG1 antibodies directed against secreted proteins acting in concert with IL-25-dependent Type 2 myeloid effector populations.

  1. Concerted Activity of IgG1 Antibodies and IL-4/IL-25-Dependent Effector Cells Trap Helminth Larvae in the Tissues following Vaccination with Defined Secreted Antigens, Providing Sterile Immunity to Challenge Infection

    Science.gov (United States)

    Hewitson, James P.; Filbey, Kara J.; Esser-von Bieren, Julia; Camberis, Mali; Schwartz, Christian; Murray, Janice; Reynolds, Lisa A.; Blair, Natalie; Robertson, Elaine; Harcus, Yvonne; Boon, Louis; Huang, Stanley Ching-Cheng; Yang, Lihua; Tu, Yizheng; Miller, Mark J.; Voehringer, David; Le Gros, Graham; Harris, Nicola; Maizels, Rick M.

    2015-01-01

    Over 25% of the world's population are infected with helminth parasites, the majority of which colonise the gastrointestinal tract. However, no vaccine is yet available for human use, and mechanisms of protective immunity remain unclear. In the mouse model of Heligmosomoides polygyrus infection, vaccination with excretory-secretory (HES) antigens from adult parasites elicits sterilising immunity. Notably, three purified HES antigens (VAL-1, -2 and -3) are sufficient for effective vaccination. Protection is fully dependent upon specific IgG1 antibodies, but passive transfer confers only partial immunity to infection, indicating that cellular components are also required. Moreover, immune mice show greater cellular infiltration associated with trapping of larvae in the gut wall prior to their maturation. Intra-vital imaging of infected intestinal tissue revealed a four-fold increase in extravasation by LysM+GFP+ myeloid cells in vaccinated mice, and the massing of these cells around immature larvae. Mice deficient in FcRγ chain or C3 complement component remain fully immune, suggesting that in the presence of antibodies that directly neutralise parasite molecules, the myeloid compartment may attack larvae more quickly and effectively. Immunity to challenge infection was compromised in IL-4Rα- and IL-25-deficient mice, despite levels of specific antibody comparable to immune wild-type controls, while deficiencies in basophils, eosinophils or mast cells or CCR2-dependent inflammatory monocytes did not diminish immunity. Finally, we identify a suite of previously uncharacterised heat-labile vaccine antigens with homologs in human and veterinary parasites that together promote full immunity. Taken together, these data indicate that vaccine-induced immunity to intestinal helminths involves IgG1 antibodies directed against secreted proteins acting in concert with IL-25-dependent Type 2 myeloid effector populations. PMID:25816012

  2. Effects of Jiaomu Oil on IL-4 and IFN-γ in bronchoalveolar lavage fluid and NF-κB in lung tissue of asthmatic model in guinea pig%椒目油对哮喘模型豚鼠肺泡灌洗液IL-4、IFN-γ水平及肺组织NF-κB的影响

    Institute of Scientific and Technical Information of China (English)

    赵睿; 戚好文; 谢柏梅

    2007-01-01

    目的 探讨椒目油对支气管哮喘(哮喘)豚鼠模型肺泡灌洗液(BALF)中IL-4、IFN-γ水平及肺组织中NF-κB的影响,为椒目油治疗哮喘提供理论依据.方法 实验分4组:正常对照组、哮喘模型组、地塞米松治疗组和椒目油治疗组,每组各10只豚鼠.用卵白蛋白(OVA)腹腔注射致敏和雾化吸入激发建立哮喘豚鼠模型.ELISA法检测豚鼠BALF中IL-4,IFN-γ含量.免疫组化法观察NF-κB在豚鼠支气管上皮的表达.结果 哮喘组BALF中的IL-4、IFN-γ含量及PC20水平都与正常对照组有显著的差别(P均<0.05),分别为(41.36±6.71) ng/L 和 (10.58±1.28) ng/L,(21.15±2.75) ng/L 和 (73.52±5.23) ng/L,(0.013±0.014) g/L 和 (0.168±0.186) g/L,而椒目油组及地塞米松治疗组豚鼠BALF中IL-4含量分别为(15.35±4.28) ng/L、(19.20±3.78) ng/L,明显低于哮喘模型组(P<0.05),其IFN-γ含量分别为(50.65±4.19) ng/L、(53.34±5.64) ng/L和PC20[(0.160±0.180) g/L、(0.144±0.154) g/L]水平较后者显著升高(P<0.05).椒目油治疗组和地塞米松治疗组各指标之间无显著性差异(P>0.05).正常对照组、哮喘模型组、椒目油治疗组和地塞米松治疗组豚鼠气道中NF-κB阳性细胞百分比分别为(9.51±2.82)%、(52.71±7.80)%、(32.26±3.70)%、(29.89±2.01)%,两治疗组均和哮喘模型组有显著差异.结论 椒目油能有效降低豚鼠BALF中IL-4水平,升高IFN-γ含量,同时降低气道高反应性和NF-κB在哮喘豚鼠支气管上皮中的表达.

  3. Effects of overexpression of IL-10, IL-12, TGF-β and IL-4 on allergen induced change in bronchial responsiveness

    Directory of Open Access Journals (Sweden)

    Lee Yueh-Lun

    2006-05-01

    Full Text Available Abstract Background An increasing prevalence of allergic diseases, such as atopic dermatitis, allergic rhinitis and bronchial asthma, has been noted worldwide. Allergic asthma strongly correlates with airway inflammation caused by the unregulated production of cytokines secreted by allergen-specific type-2 T helper (Th2 cells. This study aims to explore the therapeutic effect of the airway gene transfer of IL-12, IL-10 and TGF-β on airway inflammation in a mouse model of allergic asthma. Methods BALB/c mice were sensitized to ovalbumin (OVA by intraperitoneal injections with OVA and challenged by nebulized OVA. Different cytokine gene plasmids or non-coding vector plasmids were instilled daily into the trachea up to one day before the inhalatory OVA challenge phase. Results Intratracheal administration of IL-10, IL-12 or TGF-β can efficiently inhibit antigen-induced airway hyper-responsiveness and is able to largely significantly lower the number of eosinophils and neutrophils in bronchoalveolar lavage fluid of ovalbumin (OVA sensitized and challenged mice during the effector phase. Furthermore, the effect of IL-10 plasmids is more remarkable than any other cytokine gene plasmid. On the other hand, local administration of IL-4 gene plasmids before antigen challenge can induce severe airway hyper-responsiveness (AHR and airway eosinophilia. Conclusion Our data demonstrated that anti- inflammatory cytokines, particularly IL-10, have the therapeutic potential for the alleviation of airway inflammation in murine model of asthma.

  4. Transforming growth factor β3 attenuates the development of radiation-induced pulmonary fibrosis in mice by decreasing fibrocyte recruitment and regulating IFN-γ/IL-4 balance.

    Science.gov (United States)

    Xu, Long; Xiong, Shanshan; Guo, Renfeng; Yang, Zhihua; Wang, Qianjun; Xiao, Fengjun; Wang, Haibao; Pan, Xiujie; Zhu, Maoxiang

    2014-11-01

    Radiation-induced pulmonary fibrosis is a frequently occurred complication from radiotherapy of thoracic tumors. The transforming growth factor-β (TGF-β) superfamily plays a key regulatory role in pulmonary fibrosis. As TGF-β3 showed the potential anti-fibrotic properties especially in scar-less wound healing as opposed to the fibrotic function of TGF-β1, we sought to explore the role of TGF-β3 in radiation-induced pulmonary fibrosis. A single thoracic irradiation of 20 Gy was applied in mice to establish the model of radiation-induced pulmonary fibrosis and the mice were treated by intraperitoneal injections of recombinant TGF-β3 weekly after irradiation. We found that TGF-β3 decelerated the progress of radiation-induced pulmonary fibrosis and hindered the recruitment of fibrocytes to lung. In addition, Th1 response was suppressed as shown by diminished IFN-γ in bronchoalveolar lavage fluid (BALF) after irradiation, and enhancement of Th2 response was marked by increased IL-4 in BALF. TGF-β3 administration significantly attenuated these effects and increased the percentage of Tregs in lung during the progression of pulmonary fibrosis. Taken together, these data suggest that TGF-β3 might be involved in the regulatory mechanism for attenuation of radiation-induced pulmonary fibrosis.

  5. Transfer of in vivo primed transgenic T cells supports allergic lung inflammation and FIZZ1 and Ym1 production in an IL-4Rα and STAT6 dependent manner

    Directory of Open Access Journals (Sweden)

    Keegan Achsah D

    2011-10-01

    Full Text Available Abstract Background CD4+ T helper type 2 (TH2 cells, their cytokines IL-4, IL-5 and IL-13 and the transcription factor STAT6 are known to regulate various features of asthma including lung inflammation, mucus production and airway hyperreactivity and also drive alternative activation of macrophages (AAM. However, the precise roles played by the IL-4/IL-13 receptors and STAT6 in inducing AAM protein expression and modulating specific features of airway inflammation are still unclear. Since TH2 differentiation and activation plays a pivotal role in this disease, we explored the possibility of developing an asthma model in mice using T cells that were differentiated in vivo. Results In this study, we monitored the activation and proliferation status of adoptively transferred allergen-specific naïve or in vivo primed CD4+ T cells. We found that both the naïve and in vivo primed T cells expressed similar levels of CD44 and IL-4. However, in vivo primed T cells underwent reduced proliferation in a lymphopenic environment when compared to naïve T cells. We then used these in vivo generated effector T cells in an asthma model. Although there was reduced inflammation in mice lacking IL-4Rα or STAT6, significant amounts of eosinophils were still present in the BAL and lung tissue. Moreover, specific AAM proteins YM1 and FIZZ1 were expressed by epithelial cells, while macrophages expressed only YM1 in RAG2-/- mice. We further show that FIZZ1 and YM1 protein expression in the lung was completely dependent on signaling through the IL-4Rα and STAT6. Consistent with the enhanced inflammation and AAM protein expression, there was a significant increase in collagen deposition and smooth muscle thickening in RAG2-/- mice compared to mice deficient in IL-4Rα or STAT6. Conclusions These results establish that transfer of in vivo primed CD4+ T cells can induce allergic lung inflammation. Furthermore, while IL-4/IL-13 signaling through IL-4Rα and STAT6 is

  6. Cytokines TNF-α, IL-6, IL-17F, and IL-4 differentially affect osteogenic differentiation of human adipose stem cells

    NARCIS (Netherlands)

    A.P. Bastidas-Coral; A.D. Bakker; B. Zandieh-Doulabi; C.J. Kleverlaan; N. Bravenboer; T. Forouzanfar; J. Klein-Nulend

    2016-01-01

    During the initial stages of bone repair, proinflammatory cytokines are released within the injury site, quickly followed by a shift to anti-inflammatory cytokines. The effect of pro- and anti-inflammatory cytokines on osteogenic differentiation of mesenchymal stem cells is controversial. Here, we i

  7. Dammarane-type glycosides from Gynostemma pentaphyllum and their effects on IL-4-induced eotaxin expression in human bronchial epithelial cells.

    Science.gov (United States)

    Hung, Tran Manh; Thu, Cao Van; Cuong, To Dao; Hung, Nguyen Phi; Kwack, Seung Jun; Huh, Jung-Im; Min, Byung Sun; Choi, Jae Sue; Lee, Hyeong Kyu; Bae, KiHwan

    2010-02-26

    Two new dammarane-type glycosides, 2alpha,3beta,12beta,20S-tetrahydroxydammar-24-ene-3-O-[beta-d-glucopyranosyl(1-->4)-beta-d-glucopyranosyl]-20-O-[beta-d-xylopyranosyl-(1-->6)-beta-d-glucopyranoside] (1) and 2alpha,3beta,12beta,20S-tetrahydroxydammar-24-ene-3-O-beta-d-glucopyranosyl-20-O-[beta-d-6-O-acetylglucopyranosyl-(1-->2)-beta-d-glucopyranoside] (2), were isolated from a MeOH extract of the leaves of Gynostemma pentaphyllum. Their structures were elucidated by 1D and 2D NMR spectroscopic interpretation as well as by chemical studies. The isolated compounds showed potential inhibitory effects on eotaxin expression in BEAS-2B bronchial epithelial cells.

  8. Synergistic Induction of Eotaxin and VCAM-1 Expression in Human Corneal Fibroblasts by Staphylococcal Peptidoglycan and Either IL-4 or IL-13

    Directory of Open Access Journals (Sweden)

    Ken Fukuda

    2011-01-01

    Conclusions: Interaction of innate and adaptive immunity, as manifested by synergistic stimulation of eotaxin and VCAM-1 expression in corneal fibroblasts by peptidoglycan and Th2 cytokines, may play an important role in tissue eosinophilia associated with ocular allergy.

  9. Glomerular Diseases Associated with Hepatitis C Virus Infection

    Directory of Open Access Journals (Sweden)

    Miller Sara

    2000-01-01

    Full Text Available Renal diseases associated with hepatitis C virus (HCV infection are a significant problem for clinicians and diagnostic pathologists. A wide variety of disorders, including a spectrum of immune-complex glomerulonephritides, has been reported in association with hepatitis and cirrhosis caused by HCV. For some of these diseases, including membranoproliferative glomerulonephritis type I and cryoglobulinemic glomerulonephritis, plausible links between HCV and the glomerular pathology have been proposed. In other cases, the role of the virus in the pathogenesis of the renal disease is less certain. This communication catalogues the renal manifestations of HCV infection, providing clinical and pathological descriptions of the most prevalent disorders. Where available, evidence implicating HCV in the causation of the disorders is also discussed.

  10. Immunoregulation by naturally occurring and disease-associated autoantibodies

    DEFF Research Database (Denmark)

    Nielsen, Claus H; Bendtzen, Klaus

    2012-01-01

    -receptors on antigen-presenting cells and thereby regulate T-cell activity. Knowledge of the influence of NAbs against cytokines on immune homeostasis is likely to have wide-ranging implications both in understanding pathogenesis and in treatment of many immunoinflammatory disorders, including a number of autoimmune......The role of naturally occurring autoantibodies (NAbs) in homeostasis and in disease manifestations is poorly understood. In the present chapter, we review how NAbs may interfere with the cytokine network and how NAbs, through formation of complement-activating immune complexes with soluble self......-antigens, may promote the uptake and presentation of self-molecules by antigen-presenting cells. Both naturally occurring and disease-associated autoantibodies against a variety of cytokines have been reported, including NAbs against interleukin (IL)-1α, IL-6, IL-8, IL-10, granulocyte-macrophage colony...

  11. Inductive matrix completion for predicting gene–disease associations

    Science.gov (United States)

    Natarajan, Nagarajan; Dhillon, Inderjit S.

    2014-01-01

    Motivation: Most existing methods for predicting causal disease genes rely on specific type of evidence, and are therefore limited in terms of applicability. More often than not, the type of evidence available for diseases varies—for example, we may know linked genes, keywords associated with the disease obtained by mining text, or co-occurrence of disease symptoms in patients. Similarly, the type of evidence available for genes varies—for example, specific microarray probes convey information only for certain sets of genes. In this article, we apply a novel matrix-completion method called Inductive Matrix Completion to the problem of predicting gene-disease associations; it combines multiple types of evidence (features) for diseases and genes to learn latent factors that explain the observed gene–disease associations. We construct features from different biological sources such as microarray expression data and disease-related textual data. A crucial advantage of the method is that it is inductive; it can be applied to diseases not seen at training time, unlike traditional matrix-completion approaches and network-based inference methods that are transductive. Results: Comparison with state-of-the-art methods on diseases from the Online Mendelian Inheritance in Man (OMIM) database shows that the proposed approach is substantially better—it has close to one-in-four chance of recovering a true association in the top 100 predictions, compared to the recently proposed Catapult method (second best) that has bigdata.ices.utexas.edu/project/gene-disease. Contact: naga86@cs.utexas.edu PMID:24932006

  12. Multiple major disease-associated clones of Legionella pneumophila have emerged recently and independently

    Science.gov (United States)

    David, Sophia; Rusniok, Christophe; Mentasti, Massimo; Gomez-Valero, Laura; Harris, Simon R.; Lechat, Pierre; Lees, John; Ginevra, Christophe; Glaser, Philippe; Ma, Laurence; Bouchier, Christiane; Underwood, Anthony; Jarraud, Sophie; Harrison, Timothy G.; Parkhill, Julian; Buchrieser, Carmen

    2016-01-01

    Legionella pneumophila is an environmental bacterium and the leading cause of Legionnaires’ disease. Just five sequence types (ST), from more than 2000 currently described, cause nearly half of disease cases in northwest Europe. Here, we report the sequence and analyses of 364 L. pneumophila genomes, including 337 from the five disease-associated STs and 27 representative of the species diversity. Phylogenetic analyses revealed that the five STs have independent origins within a highly diverse species. The number of de novo mutations is extremely low with maximum pairwise single-nucleotide polymorphisms (SNPs) ranging from 19 (ST47) to 127 (ST1), which suggests emergences within the last century. Isolates sampled geographically far apart differ by only a few SNPs, demonstrating rapid dissemination. These five STs have been recombining recently, leading to a shared pool of allelic variants potentially contributing to their increased disease propensity. The oldest clone, ST1, has spread globally; between 1940 and 2000, four new clones have emerged in Europe, which show long-distance, rapid dispersal. That a large proportion of clinical cases is caused by recently emerged and internationally dispersed clones, linked by convergent evolution, is surprising for an environmental bacterium traditionally considered to be an opportunistic pathogen. To simultaneously explain recent emergence, rapid spread and increased disease association, we hypothesize that these STs have adapted to new man-made environmental niches, which may be linked by human infection and transmission. PMID:27662900

  13. Association between IL-4, IL-6 or IL-13 gene polymorphism and chronic periodontitis%IL-4、IL-6和IL-13基因多态性与慢性牙周炎的相关性研究

    Institute of Scientific and Technical Information of China (English)

    胡杉林; 秦飞; 郑江海; 代梅

    2016-01-01

    目的:研究白细胞介素-4(-34C/T和-590C/T)、6(-174G/C和-572C/G)、13(-1112C/T和+1923C/T)的基因多态性与慢性牙周炎的相关性。方法收集2013年10月至2015年10月我院口腔科收治的慢性牙周炎患者120例为CP组,另选取健康受试者120名作为对照组,选用聚合酶链反应-限制性内切酶片段长度多态性分析比较两组的基因型和等位基因分布特点。结果两组受检者IL-4-34位点、IL-4-590位点、IL-6-572位点、IL-13+1923位点的基因型和等位基因频率分布比较差异均无统计学意义(P>0.05);而IL-6-572位点、IL-13-1112位点的基因型和等位基因频率分布比较差异均有统计学意义(P0.05). But there were significant difference in the alleles and genotypes of IL-6-572 and IL-13-1112 locus between the two groups. Conclusion IL-4-34/-590, IL-6-572 and IL-13+1923 gene polymorphisms have nothing to do with chronic periodontitis, while IL-6-572 and IL-13-1112 are related to the occurrence and development of chronic periodontitis.

  14. 厄多司坦对癫痫大鼠海马氧化应激及IL-2,IL-4水平的影响%Effects of the erdosteine on oxidative stress and level of IL-2, IL-4 in hippocampus of epilepsy rats

    Institute of Scientific and Technical Information of China (English)

    李今子; 郑明慧; 尹明姬

    2012-01-01

    [目的]观察厄多司坦对海马神经元病理损伤大鼠超氧化物歧化酶(SOD)活力与丙二醛(MDA)含量变化,IL-2,IL-4含量的影响.[方法]将健康成年雄性SD大鼠随机分为正常对照组、模型对照组、厄多司坦干预组.采用Dihel点燃癫痫模型制作方法,测定各组大鼠海马组织SOD及MDA水平,采用HE染色法观察大鼠癫痫发作后的海马神经元形态学改变.采用ELISA法测定细胞因子IL-2,IL-4的含量改变.[结果] HE染色病理观察见,正常对照组无神经元坏死表现;模型对照组神经元细胞出现核固缩、碎裂和溶解,细胞坏死、脱失明显;厄多司坦干预组以神经元变性为主并有少许神经细胞坏死(P<0.01).模型对照组大鼠海马SOD活力较厄多司坦干预组及正常对照组均明显降低(P<0.01);模型对照组MDA含量较正常对照组明显升高(P<0.01),厄多司坦干预组MDA含量较模型对照组下降明显(P<0.01).模型对照组IL-2,IL-4值较正常对照组明显升高(P<0.01),厄多司坦干预组较模型对照组明显降低(P<0.01).[结论]癫痫发作时氧化应激反应、免疫-神经-内分泌系统及免疫机制参与其中;厄多司坦具有清除氧自由基、减少细胞因子的产生、保护癫痫大鼠海马神经元的作用.

  15. INTERLEUKIN-4 PREVENTS THE INDUCTION OF G-CSF MESSENGER-RNA IN HUMAN ADHERENT MONOCYTES IN RESPONSE TO ENDOTOXIN AND IL-1 STIMULATION

    NARCIS (Netherlands)

    VELLENGA, E; DOKTER, W; DEWOLF, JTM; VANDEVINNE, B; ESSELINK, MT; HALIE, MR

    Human recombinant interleukin-4 (IL-4) was studied for its effects on the expression of granulocyte-colony stimulating factor (G-CSF) mRNA in human adherent monocytes in the absence and presence of endotoxin and interleukin 1 (IL-1). IL-4 (15 ng/ml) did not induce G-CSF transcripts in monocytes but

  16. Peripheral blood T lymphocytes from asthmatic patients are primed for enhanced expression of interleukin (IL)-4 and IL-5 mRNA : associations with lung function and serum IgE

    NARCIS (Netherlands)

    Borger, P; Ten Hacken, NHT; Vellenga, E; Kauffman, HF; Postma, DS

    Background The TH2-like cytokines interleukin (IL)-4 and IL-5 play a pivotal role in airway wall inflammation in asthma and these cytokines are increased in peripheral blood and bronchoalveolar lavage fluid from asthmatic patients. It is unclear why specifically TH2-like cytokines are increased in

  17. IL-4对肝片吸虫感染诱导的巨噬细胞中脂肪酸结合蛋白2分布的影响%Effects of IL-4 on Distribution of FABP2 in Fasciola hepatica Elicited Macrophages

    Institute of Scientific and Technical Information of China (English)

    王晶; 张文韬; 王豪举; 郭智莉; 周雪梅; 周容琼; 周作勇; 罗洪林

    2012-01-01

    为阐明小鼠感染肝片吸虫后巨噬细胞中脂肪酸结合蛋白2 (FABP2)的分布,采用肝片吸虫囊蚴为感染源,经口分别感染雌性BALB/c野生型(WT)及其IL-4单抗处置小鼠,在运用特异性PCR鉴定成功感染小鼠后获取巨噬细胞,并设立人工巯基醋酸盐诱导巨噬细胞对照组进行体外培养.用荧光定量PCR检测选择性激活巨噬细胞的标记蛋白Relmα、Ym1和Arginase1以确定其激活状态.采用特异性抗体对所获取的巨噬细胞细胞质染色后用共聚焦显微镜摄取不同时间点从不同小鼠体内获取的巨噬细胞染色后的图片.野生型BALB/c巨噬细胞中Relma、Ym1和Arginase1均大量表达;IL-4单抗处置BALB/c小鼠和巯基醋酸盐诱导小鼠中巨噬细胞中的Relmα、Ym1和Arginase1的表达量较野生型小鼠中的极显著或显著下降.FABP2在FeMΦ中并不分布于细胞质膜下,而是呈点状广泛分布于细胞质中,其荧光强度在12~24 h间呈上升趋势,在24~48 h间却呈下降趋势.%Macrophages were acquired from the F. hepatica metacercariae infected IL-4 monoclonal antibody treated and wild type female BALB/c mice, respectively. All F. hepatica elicited macrophages and control macrophages were cultured in vitro. mRNAs from macrophages were extracted for the detection of Relma, Ym1 and Arginasel genes using Real-time poly-merase chain reaction. Pictures and fluorescence intensity at different time points were acquired with a confocal microscopy and image software respectively after staining with serial purified antibodies. Results showed that levels of Relmα, Yml and Arginasel in F. hepatica elicited macrophages (FeMΦ) and control macrophages (TeMΦ) from IL-4 monoclonal antibody treated mice were significantly decreased comparison to that in wild type mice. FABP2 was detected as spots in the cytoplasm. The fluorescence intensity of FABP2 increased from 12 to 24 h, but decreased afterward to 48 h. The fluorescence intensity of

  18. Associations of IL-4, IL-6, and IL-12 levels in peripheral blood with lung function, cellular immune function, and quality of life in children with moderate-to-severe asthma

    Science.gov (United States)

    Cui, Ai-Hua; Zhao, Jing; Liu, Shu-Xiang; Hao, Ying-Shuang

    2017-01-01

    Abstract Background: Pediatric asthma has gained increasing concerns with poorly understood pathogenesis. The purpose of this study was to explore the associations of interleukin-4 (IL-4), IL-6, and IL-12 levels in peripheral blood (PB) with lung function, cellular immune function, and children's quality of life (QOL) with moderate-to-severe asthma. Methods: A total of 1158 children with moderate-to-severe asthma (the experimental group) and 1075 healthy children (the control group) were recruited for our study. Enzyme-linked immunosorbent assay was used to detect IL-4, IL-6, and IL-12 levels. T lymphocytes were detected by alkaline phosphatase antialkaline phosphatase, and erythrocyte immune was measured by red blood cell C 3b receptor (RBC-C3bR) rosette-forming test. The forced expiratory volume in 1 second (FEV1) and peak expiratory flow (PEF) were detected, after which FEV1/forced vital capacity (FVC) was calculated before and after treatment. PedsQL3.0 was used to measure the effect of asthma on QOL of children, and the correlation between IL-4, IL-6, and IL-12 levels and the lung function and QOL was measured. Logistic regression analysis was applied to detect related factors of moderate-to-severe asthma of children. Results: After treatment, the decreased IL-4 and IL-6 levels and increased IL-12 level were revealed in the experimental group. The cellular immune function's disorder was significantly decreased, and an elevated CD3, CD4, CD8, and declined CD4/CD8 level was performed in T lymphocytes. RBC-C3bR was increased, and red blood cell immune complex (RBC-IC) was reduced in erythrocyte immune in comparison with those before treatment. Lung function parameters all increased. After treatment, the symptoms of asthma in children reduced with scores of increased QOL. IL-4 was positively related to RBC-IC, but negatively associated with the QOL score. IL-6 showed negative connection with CD4/CD8, RBC-C3bR, FEV1/FVC, and QOL score, and had positive connection

  19. Associations of IL-4, IL-6, and IL-12 levels in peripheral blood with lung function, cellular immune function, and quality of life in children with moderate-to-severe asthma.

    Science.gov (United States)

    Cui, Ai-Hua; Zhao, Jing; Liu, Shu-Xiang; Hao, Ying-Shuang

    2017-03-01

    Pediatric asthma has gained increasing concerns with poorly understood pathogenesis. The purpose of this study was to explore the associations of interleukin-4 (IL-4), IL-6, and IL-12 levels in peripheral blood (PB) with lung function, cellular immune function, and children's quality of life (QOL) with moderate-to-severe asthma. A total of 1158 children with moderate-to-severe asthma (the experimental group) and 1075 healthy children (the control group) were recruited for our study. Enzyme-linked immunosorbent assay was used to detect IL-4, IL-6, and IL-12 levels. T lymphocytes were detected by alkaline phosphatase antialkaline phosphatase, and erythrocyte immune was measured by red blood cell C 3b receptor (RBC-C3bR) rosette-forming test. The forced expiratory volume in 1 second (FEV1) and peak expiratory flow (PEF) were detected, after which FEV1/forced vital capacity (FVC) was calculated before and after treatment. PedsQL3.0 was used to measure the effect of asthma on QOL of children, and the correlation between IL-4, IL-6, and IL-12 levels and the lung function and QOL was measured. Logistic regression analysis was applied to detect related factors of moderate-to-severe asthma of children. After treatment, the decreased IL-4 and IL-6 levels and increased IL-12 level were revealed in the experimental group. The cellular immune function's disorder was significantly decreased, and an elevated CD3, CD4, CD8, and declined CD4/CD8 level was performed in T lymphocytes. RBC-C3bR was increased, and red blood cell immune complex (RBC-IC) was reduced in erythrocyte immune in comparison with those before treatment. Lung function parameters all increased. After treatment, the symptoms of asthma in children reduced with scores of increased QOL. IL-4 was positively related to RBC-IC, but negatively associated with the QOL score. IL-6 showed negative connection with CD4/CD8, RBC-C3bR, FEV1/FVC, and QOL score, and had positive connection with PEF. In addition, IL-12 was

  20. Expression of chemokine receptors CCR3,CCR5 and CXCR3 on CD4+ T cells in CBA/JxDBA/2 mouse model,selectively induced by IL-4 and IL-10,regulates the embryo resorption rate

    Institute of Scientific and Technical Information of China (English)

    JIANG Pei-juan; ZHAO Ai-min; BAO Shi-min; XIAO Shi-jin; XIONG Miao

    2009-01-01

    Background Chemokines and their receptors have been a research focus in transplantation immunology.Chemokines and their receptors play a role in lymphocyte recruitment and differentiation process.This study aimed to observe whether IL-4 and IL-10 may regulate the expression of chemokine receptors CCR3,CCR5 and CXCR3 on CD4+ T cells in CBA/JxDBA/2 mouse model and to explore the role of CCR3,CCR5,CXCR3 in immune tolerance in pregnancy.Methods The mouse model of spontaneous abortion (CBA/JxDBA/2) and the normal pregnant mouse model (CBA/JxBALB/c) were used.CBA/JxDBA/2 mice were injected with IL-4 (CBA/JxDBA/2-1L-4),IL-4 and IL-10 (CBA/JxDBA/2-1L-4+IL-10),or normal saline (CBA/JxDBA/2-NS) as a control.The expression of CCR3,CCR5 and CXCR3 on CD4+ T cells from mouse peripheral blood was measured by the double-labelled FCM method,and the embryo resorption rate was also examined.Results The embryo resorption rate in the CBA/JxDBA/2 group without any treatment was significantly higher than that in the CBA/JxBALB/c group (17.9% vs 3.7%,P<0.01).The embryo resorption rate in the CBA/JxDBA/2 group immunized with IL-4 or IL-4 together with IL-10 was significantly decreased,compared with that in the control and NS groups respectively.CCR3 expression on CD4+ T cells in the CBA/JxDBA/2 group without any treatment was significantly lower than that in the CBA/JxBALB/c group (0.3738±0.3575 vs 1.2190±0.2772,P<0.01 );both CCR5 (3.0900±1.5603 vs 1.2390±0.6361,P <0.01)and CXCR3 (2.4715±0.9074 vs 0.9200±0.5585,P <0.01 ) expressions on CD4+ T cells of the CBA/JxDBA/2 group without any treatment were significantly higher than those of the CBA/JxBALB/c group.Significant up-regulation of CCR3 and down-regulation of CXCR3 were found in the CBA/JxDBA/2 group treated with IL-4 (CCR3:2.0360±0.6944,CXCR3:1.3510±0.5263,P <0.01) or IL-4 and IL-10 (CCR3:1.8160±1.0947,CXCR3:1.0940±0.7168,P<0.01).Because of the CCR5,IL-4 and IL-10 (1.9400±0.8504 vs 3.0900±1.5603,P <0.05),but

  1. 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.

  2. Assessment of genetic associations between common single nucleotide polymorphisms in RIG-I-like receptor and IL-4 signaling genes and severe respiratory syncytial virus infection in children: a candidate gene case-control study.

    Directory of Open Access Journals (Sweden)

    Nico Marr

    Full Text Available The majority of cases of severe pediatric respiratory syncytial virus (RSV infection occur in otherwise healthy infants who have no identifiable risk factors, suggesting that additional subclinical factors, such as population genetic variation, influence the course of RSV infection. The objective of this study was to test if common single nucleotide polymorphisms (SNPs in genes encoding for immune signalling components of the RIG-I-like receptor (RLR and IL-4-signalling pathways affect the outcome of RSV infection in early life. We genotyped 8 SNPs using allele-specific probes combined with real-time PCR. Each of the SNPs tested had previously been established to have a functional impact on immune responsiveness and two of the SNPs in the IL4 and IL4R genes had previously been associated with severe RSV bronchiolitis. Association with susceptibility to severe RSV infection was tested by statistically comparing genotype and allele frequencies in infants and young children hospitalized with severe RSV bronchiolitis (n = 140 with two control groups-children who tested positive for RSV but did not require hospitalization (n = 100, and a general population control group (n = 285. Our study was designed with sufficient power (>80% to detect clinically-relevant associations with effect sizes ≥1.5. However, we detected no statistically significant differences in allele and genotype frequencies of the investigated SNPs between the inpatient and control groups. To conclude, we could not replicate the previously reported association with SNPs in the IL4 and IL4R genes in our independent cohort, nor did we find that common SNPs in genes encoding for RLRs and the downstream adapter MAVS were associated with susceptibility to severe RSV infections. Despite the existing evidence demonstrating a functional immunological impact of these SNPs, our data suggest that the biological effect of each individual SNP is unlikely to affect clinical outcomes

  3. 哮喘患儿血清中sIL-2R、IL-2、IL-4、IL-13的水平变化与临床意义

    Institute of Scientific and Technical Information of China (English)

    许文龙; 张国祥; 楚旭

    2007-01-01

    [目的]探讨哮喘患儿清中可溶性白细胞介素-2受体(sIL-2R)、白细胞介素-2(IL-2)、白细胞介素-4(IL-4)、白细胞介素-13(IL-13)的水平变化及其与哮喘发病机制的关系.[方法]每例样本均取空腹静脉血并即时分离血清1 ml,用ELISA法检测血清中sIL-2R、IL-2、IL-4、IL-13的水平并对结果进行统计学分析.[结果]哮喘急性发作组、缓解组的血清中sIL-2R、IL-2、IL-4、IL-13的结果与正常对照组比较差异均有显著性(P<0.05).其中哮喘急性发作组、缓解组血清中sIL-2R,IL-4、IL-13的结果要明显高于正常对照组,而IL-2则明显低于正常对照组.此外,哮喘急性发作组与缓解组血清中IL-2、IL-4、IL-13的结果相比较差异均有显著性(P均<0.05),而SIL-2R则无明显差异.[结论]哮喘患儿血清中sIL-2R、IL-2、IL-4、IL-13的水平伴随病情进展发生显著的变化,说明它们在哮喘的免疫病理过程中起着重要的作用.

  4. IL-4RaArg55、IgE与API阳性婴幼儿喘息的相关性研究%Correlation of IL-4RaArg55 and IgE Levels with API Positive Infantile Wheezing

    Institute of Scientific and Technical Information of China (English)

    王建荣; 齐英征; 吴英杰

    2015-01-01

    目的 探讨白介素4受体基因Arg55(IL-4RaArg55)、IgE在哮喘预测指数(asthma predicting index,API)阳性患儿中的应用价值.方法 选取同期的年龄在1月至3岁喘息婴幼儿356例,分为API阳性组167例,API阴性组189例,同时设立对照组203例,首先应用PCR聚合酶链反应和DNA测序法对两组基因进行分型,并用ELISA法检测IgE水平,进一步根据年龄、性别进行组内分层,进行IgE水平统计分析.结果 ①IL-4RaArg55位点各基因型频率分布在API(+)组、API(-)组、对照组3组中差异无统计学意义(AA基因:x2 =2.16,P=0.35;x2=0.77,P=0.68;x2 =4.11,P=0.13;A等位基因:x2=0.48,P =0.49;x2=0.71,P=0.40;x2 =2.58,P=0.11).②API(+)、API(-)及对照组间IgE水平分别为93.18±40.79、54.16±22.66、48.82±21.42 U/mL,3组差异有统计学意义(H=377.419,P=0.000),API(+)组远高于API(-)及对照组.③API(+)组内<2岁与≥2岁IgE水平相互比较,差异有统计学意义(t'=9.281,P<0.001);API(-)组内<2岁与≥2岁IgE水平相互比较,差异无统计学意义(t=0.693,P=0.489).④API(+)组及API(-)组内男性与女性IgE水平相互比较,差异无统计学意义[API(+) t=1.598,P=0.112,API(-)t=0.330,P=0.742].结论 ①IL-4RaArg55多态性与API结果无相关性;②血清IgE水平与API阳性有相关性,对≥2岁的婴幼儿喘息的预后判断有一定的意义.

  5. Inflammatory bowel disease associations with HLA Class II genes

    Energy Technology Data Exchange (ETDEWEB)

    Castro, R. [Cedars-Sinai Medical Center, Los Angeles, CA (United States); Yang, H.; Targan, S. [Roche Molecular Systems, Inc., Alameda, CA (United States)] [and others

    1994-09-01

    A PCR-SSOP assay has been used to analyze HLA-Class II DRB1 and DQB1 alleles in 378 Caucasians from a population in Southern California. The data has been analyzed separately for the Ashkenasi Jews and non-Jewish patients (n=286) and controls (n=92). Two common clinical forms of inflammatory bowel disease (IBD) have been studied: ulcerative colitis (UC) and Crohn`s disease (CD). In CD, we observed a susceptible effect with the rare DR1 allele - DRB*0103 [O.R.=4.56; 95% CI (0.96, 42.97); p=0.03]; a trend for an increase in DRB1*0103 was also observed in UC patients. A susceptible effect with DRB1*1502 [O.R.=5.20; 95% CI (1.10, 48.99); p=0.02] was observed in non-Jewish UC patients. This susceptible effect was restricted to UC ANCA-positive (antineutrophil cytoplasmic antibodies) patients. In addition, a significant association with DRB1*1101-DQB1*0301 [O.R.=9.46; 95% CI (1.30, 413.87); p=0.01] was seen with UC among non-Jewish patients: this haplotype was increased with CD among non-Jewish patients. Two protective haplotypes were detected among CD non-Jewish patients: DRB1*1301-DQB1*0603 [O.R.=0.34; 95% CI (0.09, 1.09); p=0.04], and DRB*0404-DQB1*0302 [O.R.=<0.08; 95% CI (0.0, 0.84); p=0.01]. When the same data were analyzed at the serology level, we observed a positive association in UC with DR2 [O.R.6.77; 95% CI (2.47, 22.95); p=2 x 10{sup -4}], and a positive association in CD with DR1 [O.R.=2.63; 95% CI (1.14, 6.62); p=0.01] consistent with previous reports. Thus, some IBD disease associations appear to be common to both UC and CD, while some are unique to one disease.

  6. Clinical Observation of the Method of Removing Phlegm-Heat and Promoting Blood Circulation in Treating Acne with Phlegm Accumulate with Stagnant Blood Syndrome and Effect on Serum IL-4, IFN-γ%清热化痰活血法治疗痰瘀互结型痤疮疗效观察及对血清IL-4,IFN-γ的影响

    Institute of Scientific and Technical Information of China (English)

    张虹亚; 许光仓; 曹宇; 刘涛峰; 吴敏; 王建锋; 孙洪波

    2012-01-01

    Objective To observe the clinical effect of the method of removing phlegm-heat and promoting blood circulation in treating acne with phlegm accumulate with stagnant blood syndrome. Methods Ninety patients with phlegm accumulate with stagnant blood syndrome of acne were randomly divided into treatment group and control. 51 patients in treatment group were treated with the method of removing phlegm-heat and promoting Blood circulation, 39 patients in control group took danshentong capsule, the treatment duration was 12 weeks. The levels of serum IL-4 and IFN-7 were detected before and after the treatment. Results The total effective rate was 49.02% in treatment group, which was higher than that in the control group(41.02%). There was no significant difference between the two groups (P> 0.05). After the treatment , the level of Iiy-4 decreased and the level of IFN-"y increased significant in two groups (P < 0.01). Conclusion Clinical effi cacy of the method of removing phlegm-heat and promoting Blood circulation was obvious, which can decrease the level of IL-4 and increase the level of IFN--y.%目的 观察清热化痰活血法对痰瘀互结型痤疮的临床疗效.方法 90例痰瘀互结型痤疮患者随机分为两组,治疗组51例用清热化痰活血方,1剂/d,水煎分2次服用,对照组39例口服丹参酮胶囊1g,3次-/d,4周为一疗程,两组均治疗3个疗程.同时检测两组治疗前后血清IL-4,IFN-γ水平.结果 治疗组有效率为49.02%,对照组41.02%,两组差异无统计学意义(P>0.05).治疗后两组的IL-4,FN-γ均有不同的变化,IL-4水平降低,IFN-γ水平升高,与治疗前相比差异有统计学意义(P<0.01).结论 清热化痰活血法能明显改善痰瘀互结型痤疮患者的临床症状,降低IL-4水平,升高IFN-γ水平.

  7. Plasma Inflammatory Cytokine IL-4, IL-8, IL-10, and TNF-α Levels Correlate with Pulmonary Function in Patients with Asthma-Chronic Obstructive Pulmonary Disease (COPD) Overlap Syndrome.

    Science.gov (United States)

    Huang, Ai-Xia; Lu, Li-Wen; Liu, Wen-Juan; Huang, Mao

    2016-08-09

    BACKGROUND The aim of this study was to investigate the plasma inflammatory cytokine levels and their correlations with pulmonary function in patients with asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS). MATERIAL AND METHODS Between January 2013 and December 2014, a total of 96 patients with asthma, acute exacerbation of chronic obstructive pulmonary disease (AECOPD), or ACOS were enrolled, and 35 healthy people were included as a control group. Fasting plasma interleukin (IL)-4, IL-8, IL-10, and tumor necrosis factor alpha (TNF-α) levels were detected using enzyme-linked immunosorbent assay (ELISA). Correlations between the plasma inflammatory cytokine levels and forced expiratory volume in 1 second (FEV1), FEV1/predicted value ratio (FEV1%pred), and FEV1/forced vital capacity (FVC) were analyzed. RESULTS IL-4 and IL-8 levels showed statistically significant differences among the 3 groups of patients (both PCOPD, and ACOS.

  8. Functional Assessment of Disease-Associated Regulatory Variants In Vivo Using a Versatile Dual Colour Transgenesis Strategy in Zebrafish

    Science.gov (United States)

    Bhatia, Shipra; Gordon, Christopher T.; Foster, Robert G.; Melin, Lucie; Abadie, Véronique; Baujat, Geneviève; Vazquez, Marie-Paule; Amiel, Jeanne; Lyonnet, Stanislas; van Heyningen, Veronica; Kleinjan, Dirk A.

    2015-01-01

    Disruption of gene regulation by sequence variation in non-coding regions of the genome is now recognised as a significant cause of human disease and disease susceptibility. Sequence variants in cis-regulatory elements (CREs), the primary determinants of spatio-temporal gene regulation, can alter transcription factor binding sites. While technological advances have led to easy identification of disease-associated CRE variants, robust methods for discerning functional CRE variants from background variation are lacking. Here we describe an efficient dual-colour reporter transgenesis approach in zebrafish, simultaneously allowing detailed in vivo comparison of spatio-temporal differences in regulatory activity between putative CRE variants and assessment of altered transcription factor binding potential of the variant. We validate the method on known disease-associated elements regulating SHH, PAX6 and IRF6 and subsequently characterise novel, ultra-long-range SOX9 enhancers implicated in the craniofacial abnormality Pierre Robin Sequence. The method provides a highly cost-effective, fast and robust approach for simultaneously unravelling in a single assay whether, where and when in embryonic development a disease-associated CRE-variant is affecting its regulatory function. PMID:26030420

  9. single nucleotide Polymorphisms rs2227284, rs2243283 and rs2243288 in the Il-4 Gene show no association with susceptibility to Chronic Hepatitis B in a Chinese Han Population

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    Objective To investigate the relationship between single nucleotide polymorphisms (SNPs) of the interleukin-4 (IL-4) gene and outcome of hepatitis B virus (HBV) infection in a Chinese Han population. Methods Total of 501 patients with chronic hepatitis B virus (HBV) infection and 301 controls with self-limiting HBV infection were studied. Three tag SNPs in the IL-4 gene (rs2227284G/T, rs2243283C/G and rs2243288A/G) were genotyped by the Multiplex snapshot technique. The genotype and allele frequencies were calculated and analyzed. Results The three SNPs showed no significant genotype/allele associations with chronic HBV infection. Overall allele P values were:rs2227284, P=0.655, odds ratio (OR) [95%conifdence interval (CI)]=1.070 (0.793-1.445);rs2243283, P=0.849, OR (95%CI)=0.976 (0.758-1.257);rs2243288, P=0.659, OR (95%CI) = 1.060 (0.818-1.375). Overall genotype P values were: rs2227284, P = 0.771; rs2243283, P = 0.571;rs2243288, P=0.902. There were no statistically signiifcant differences between patients with chronic HBV infection and controls. Haplotypes generated by these three SNPs also had no signiifcant differences between the two groups. Conclusions The three tag SNPs of IL-4 were not associated with the outcome of HBV infection in the Han Chinese population.

  10. Impact of the IL-4 -590 C/T transition on the levels of Plasmodium falciparum specific IgE, IgG, IgG subclasses and total IgE in two sympatric ethnic groups living in Mali.

    Science.gov (United States)

    Vafa, Manijeh; Maiga, Bakary; Israelsson, Elisabeth; Dolo, Amagana; Doumbo, Ogobara K; Troye-Blomberg, Marita

    2009-01-01

    This study aimed to examine the effect of IL-4 -590 T/C polymorphism on the levels of malaria-specific IgE, IgG, IgG (1-4) subclasses as well as total IgE in the Fulani and their sympatric ethnic group, the Dogon, in Mali. Asymptomatic individuals, of the Fulani and the Dogon ethnic groups, were included in the study. IL-4 is involved in the regulation of IgE and IgG4 subclass. In line with this we found that within the Fulani, the T allele was associated with increased levels of total and anti-malarial IgE (P=0.02 and P=0.04, respectively). The Fulani T allele carriers had slightly higher levels of malarial specific IgG4 as compared to those with the CC genotype (P=0.08). No such differences were observed amongst the Dogon individuals. Taken together, these data indicate that the impact of IL-4 -590 variants on antibody levels may vary in different ethnic populations, and that this might affect the Ig-class and subclass distributions.

  11. IL-2 and IFN-gamma, but not IL-4 secretion by peripheral blood mononuclear cells (PBMC) are related to CD4+ T cells and clinical status in Brazilian HIV-1-infected subjects.

    Science.gov (United States)

    Hong, M A; Wakim, V L; Salomão, S J; Camargo, L S; Casseb, J; Duarte, A J

    1998-01-01

    It has been reported that production of IL-2 and IFN-gamma, known as T-helper type 1 cytokines, by peripheral mononuclear cells (PBMC) decreases with progression of HIV infection. In contrast, IL-4 and IL-10 production, Th2 cytokine profile, increases with HIV disease progression. PBMC were evaluated from 55 HIV-infected subjects from Divisão de Imunologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, to "in vitro" cytokines production after 24 hours of stimulation with PHA. Low levels of IL-4 production in both HIV-infected patients and normal subjects, were detected. The patients with CD4+ T cell counts 500 cells/mm3) also showed decreased production of IL-2 that was not statistically significant. There was a correlation between IL-2 and IFN-gamma release with CD4+ T cells counts. HIV-1-infected individuals with CD4+ T cells > 500 cells/mm3 showed increased levels of IL-2 and IFN-gamma, than individuals with CD4+ T cells < 500 cells/mm3. In conclusion, we observed a decline of IL-2 and IFN-gamma production at advanced HIV disease. IL-4 production was not affected during HIV infection. Taken together, these findings suggest that the cytokine profile might be influenced by the HIV infection rather than the cause of disease progression.

  12. IL-2 AND IFN-g, BUT NOT IL-4 SECRETION BY PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMC ARE RELATED TO CD4+ T CELLS AND CLINICAL STATUS IN BRAZILIAN HIV-1-INFECTED SUBJECTS

    Directory of Open Access Journals (Sweden)

    Marisa A. HONG

    1998-11-01

    Full Text Available It has been reported that production of IL-2 and IFN-g, known as T-helper type 1 cytokines, by peripheral mononuclear cells (PBMC decreases with progression of HIV infection. In contrast, IL-4 and IL-10 production, Th2 cytokine profile, increases with HIV disease progression. PBMC were evaluated from 55 HIV-infected subjects from Divisão de Imunologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, to "in vitro" cytokines production after 24 hours of stimulation with PHA. Low levels of IL-4 production in both HIV- infected patients and normal subjects, were detected. The patients with CD4+ T cell counts g production compared to controls. Patients with higher counts of CD4+ T cells (either between 200-500 or >500 cells/mm3 also showed decreased production of IL-2 that was not statistically significant. There was a correlation between IL-2 and IFN-g release with CD4+ T cells counts. HIV-1-infected individuals with CD4+ T cells >500 cells/mm3 showed increased levels of IL-2 and IFN-g, than individuals with CD4+ T cells g production at advanced HIV disease. IL-4 production was not affected during HIV infection. Taken together, these findings suggest that the cytokine profile might be influenced by the HIV infection rather than the cause of disease progression.

  13. Activation of the TLR/MyD88/NF-κB signal pathway contributes to changes in IL-4 and IL-12 production in piglet lymphocytes infected with porcine circovirus type 2 in vitro.

    Directory of Open Access Journals (Sweden)

    Dianning Duan

    Full Text Available Porcine circovirus type 2 (PCV2 causes immunosuppression in pigs. One causative factor is an imbalance in cytokine levels in the blood and lymphoid tissues. Many studies have reported changes in cytokine production, but the regulatory mechanisms involved have not yet been elucidated. In this study, we investigated alteration and regulation of IL-4 and IL-12 production in lymphocytes following incubation with PCV2 in vitro. The levels of IL-4 decreased and levels of IL-12 increased in lymphocyte supernatants, and the DNA-binding activity of NF-κB and the expression of p65 in the nucleus and p-IκB in the cytoplasm of lymphocytes increased after incubation with PCV2. However, these effects were reversed when lymphocytes were coincubated with PCV2 and the NF-κB inhibitor BAY11-7082. In addition, the expression of MyD88 protein increased and the expression of mRNA for the toll-like receptors (TLRs TLR2, TLR3, TLR4 and TLR9 was upregulated when lymphocytes were incubated with PCV2. However, no change was seen in TLR7 and TLR8 mRNA expression. In conclusion, this study showed that PCV2 induced a decrease in IL-4 and an increase in IL-12 production in lymphocytes, and these changes were regulated by the TLR-MyD88-NF-κB signal pathway.

  14. Moyamoya disease associated with an anterior inferior cerebellar artery arising from a persistent trigeminal artery

    Energy Technology Data Exchange (ETDEWEB)

    Uchino, A.; Sawada, A.; Takase, Y.; Kudo, S. [Department of Radiology, Saga Medical School, 5-1-1, Nabeshima, Saga, 849-8501 (Japan); Koizumi, T. [Department of Neurosurgery, Saga Medical School, 5-1-1, Nabeshima, Saga, 849-8501 (Japan)

    2002-07-01

    The authors present a case of moyamoya disease associated with a persistent trigeminal artery from which the anterior inferior cerebellar artery arose. We reviewed previously reported cases of moyamoya disease associated with persistent carotid-basilar arterial anastomosis and investigated the embryology of this rare arterial variation. (orig.)

  15. Mutations of SURF-1 in Leigh disease associated with cytochrome c oxidase deficiency.

    Science.gov (United States)

    Tiranti, V; Hoertnagel, K; Carrozzo, R; Galimberti, C; Munaro, M; Granatiero, M; Zelante, L; Gasparini, P; Marzella, R; Rocchi, M; Bayona-Bafaluy, M P; Enriquez, J A; Uziel, G; Bertini, E; Dionisi-Vici, C; Franco, B; Meitinger, T; Zeviani, M

    1998-12-01

    Leigh disease associated with cytochrome c oxidase deficiency (LD[COX-]) is one of the most common disorders of the mitochondrial respiratory chain, in infancy and childhood. No mutations in any of the genes encoding the COX-protein subunits have been identified in LD(COX-) patients. Using complementation assays based on the fusion of LD(COX-) cell lines with several rodent/human rho0 hybrids, we demonstrated that the COX phenotype was rescued by the presence of a normal human chromosome 9. Linkage analysis restricted the disease locus to the subtelomeric region of chromosome 9q, within the 7-cM interval between markers D9S1847 and D9S1826. Candidate genes within this region include SURF-1, the yeast homologue (SHY-1) of which encodes a mitochondrial protein necessary for the maintenance of COX activity and respiration. Sequence analysis of SURF-1 revealed mutations in numerous DNA samples from LD(COX-) patients, indicating that this gene is responsible for the major complementation group in this important mitochondrial disorder.

  16. Parsing the Interferon Transcriptional Network and Its Disease Associations.

    Science.gov (United States)

    Mostafavi, Sara; Yoshida, Hideyuki; Moodley, Devapregasan; LeBoité, Hugo; Rothamel, Katherine; Raj, Towfique; Ye, Chun Jimmie; Chevrier, Nicolas; Zhang, Shen-Ying; Feng, Ting; Lee, Mark; Casanova, Jean-Laurent; Clark, James D; Hegen, Martin; Telliez, Jean-Baptiste; Hacohen, Nir; De Jager, Philip L; Regev, Aviv; Mathis, Diane; Benoist, Christophe

    2016-01-28

    Type 1 interferon (IFN) is a key mediator of organismal responses to pathogens, eliciting prototypical "interferon signature genes" that encode antiviral and inflammatory mediators. For a global view of IFN signatures and regulatory pathways, we performed gene expression and chromatin analyses of the IFN-induced response across a range of immunocyte lineages. These distinguished ISGs by cell-type specificity, kinetics, and sensitivity to tonic IFN and revealed underlying changes in chromatin configuration. We combined 1,398 human and mouse datasets to computationally infer ISG modules and their regulators, validated by genetic analysis in both species. Some ISGs are controlled by Stat1/2 and Irf9 and the ISRE DNA motif, but others appeared dependent on non-canonical factors. This regulatory framework helped to interpret JAK1 blockade pharmacology, different clusters being affected under tonic or IFN-stimulated conditions, and the IFN signatures previously associated with human diseases, revealing unrecognized subtleties in disease footprints, as affected by human ancestry.

  17. Next-Generation Sequencing of the HLA locus: Methods and impacts on HLA typing, population genetics and disease association studies.

    Science.gov (United States)

    Carapito, Raphael; Radosavljevic, Mirjana; Bahram, Seiamak

    2016-11-01

    The human Major Histocompatibility Complex, known as the "Human Leukocyte Antigen (HLA)", could be defined as a "super locus" (historically called "supergene") governing the adaptive immune system in vertebrates. It also harbors genes involved in innate immunity. HLA is the most gene-dense, polymorphic and disease-associated region of the human genome. It is of critical medical relevance given its involvement in the fate of the transplanted organs/tissues and its association with more than 100 diseases. However, despite these important roles, comprehensive sequence analysis of the 4 megabase HLA locus has been limited due to technological challenges. Thanks to recent improvements in Next-Generation Sequencing (NGS) technologies however, one is now able to handle the peculiarities of the MHC notably the tight linkage disequilibrium between genes as well as their high degree of polymorphism (and hence heterozygosity). Increased read lengths, throughput, accuracy, as well as development of new bioinformatics tools now enable to efficiently generate complete and accurate full-length HLA haplotypes without phase ambiguities. The present report reviews current NGS approaches to capture, sequence and analyze HLA genes and loci. The impact of these new methodologies on various applications including HLA typing, population genetics and disease association studies are discussed. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  18. Disease-associated XMRV sequences are consistent with laboratory contamination

    Directory of Open Access Journals (Sweden)

    Garson Jeremy A

    2010-12-01

    Full Text Available Abstract Background Xenotropic murine leukaemia viruses (MLV-X are endogenous gammaretroviruses that infect cells from many species, including humans. Xenotropic murine leukaemia virus-related virus (XMRV is a retrovirus that has been the subject of intense debate since its detection in samples from humans with prostate cancer (PC and chronic fatigue syndrome (CFS. Controversy has arisen from the failure of some studies to detect XMRV in PC or CFS patients and from inconsistent detection of XMRV in healthy controls. Results Here we demonstrate that Taqman PCR primers previously described as XMRV-specific can amplify common murine endogenous viral sequences from mouse suggesting that mouse DNA can contaminate patient samples and confound specific XMRV detection. To consider the provenance of XMRV we sequenced XMRV from the cell line 22Rv1, which is infected with an MLV-X that is indistinguishable from patient derived XMRV. Bayesian phylogenies clearly show that XMRV sequences reportedly derived from unlinked patients form a monophyletic clade with interspersed 22Rv1 clones (posterior probability >0.99. The cell line-derived sequences are ancestral to the patient-derived sequences (posterior probability >0.99. Furthermore, pol sequences apparently amplified from PC patient material (VP29 and VP184 are recombinants of XMRV and Moloney MLV (MoMLV a virus with an envelope that lacks tropism for human cells. Considering the diversity of XMRV we show that the mean pairwise genetic distance among env and pol 22Rv1-derived sequences exceeds that of patient-associated sequences (Wilcoxon rank sum test: p = 0.005 and p pol and env, respectively. Thus XMRV sequences acquire diversity in a cell line but not in patient samples. These observations are difficult to reconcile with the hypothesis that published XMRV sequences are related by a process of infectious transmission. Conclusions We provide several independent lines of evidence that XMRV detected by

  19. Human basophils express interleukin-4 receptors

    Energy Technology Data Exchange (ETDEWEB)

    Valent, P.; Besemer, J.; Kishi, K.; Di Padova, F.; Geissler, K.; Lechner, K.; Bettelheim, P. (Univ. of Vienna (Austria))

    1990-11-01

    Interleukin-4 (IL-4), a multipotential lymphokine reputed to play an important role in the regulation of immune responses, interacts with a variety of hemopoietic target cells through specific cell surface membrane receptors. The present study was designed to investigate whether human basophils express IL-4 binding sites. For this purpose, basophils were enriched to homogeneity (93% and 98% purity, respectively) from the peripheral blood of two chronic granulocytic leukemia (CGL) donors using a cocktail of monoclonal antibodies (MoAbs) and complement. Purified basophils bound 125I-radiolabeled recombinant human (rh) IL-4 in a specific manner. Quantitative binding studies and Scatchard plot analysis revealed the presence of a single class of high affinity IL-4 binding sites (280 +/- 40 sites per cell in donor 1 and 640 +/- 45 sites per cell in donor 2) with an apparent dissociation constant, kd, of 7.12 x 10(-11) +/- 2.29 x 10(-11) and 9.55 +/- 3.5 x 10(-11) mol/L, respectively. KU812-F, a human basophil precursor cell line, was found to express a single class of 810 to 1,500 high affinity IL-4 binding sites with a kd of 2.63 to 5.54 x 10(-10) mol/L. No change in the numbers or binding constants of IL-4 receptors was found after exposure of KU812-F cells to rhIL-3 (a potent activator of basophils) for 60 minutes. No effect of rhIL-4 on 3H-thymidine uptake, release or synthesis of histamine, or expression of basophil differentiation antigens (Bsp-1, CD11b, CD25, CD40, CD54) on primary human CGL basophils or KU812-F cells was observed.

  20. Informatics-Based Discovery of Disease-Associated Immune Profiles

    Science.gov (United States)

    Delmas, Amber; Oikonomopoulos, Angelos; Lacey, Precious N.; Fallahi, Mohammad; Hommes, Daniel W.; Sundrud, Mark S.

    2016-01-01

    Advances in flow and mass cytometry are enabling ultra-high resolution immune profiling in mice and humans on an unprecedented scale. However, the resulting high-content datasets challenge traditional views of cytometry data, which are both limited in scope and biased by pre-existing hypotheses. Computational solutions are now emerging (e.g., Citrus, AutoGate, SPADE) that automate cell gating or enable visualization of relative subset abundance within healthy versus diseased mice or humans. Yet these tools require significant computational fluency and fail to show quantitative relationships between discrete immune phenotypes and continuous disease variables. Here we describe a simple informatics platform that uses hierarchical clustering and nearest neighbor algorithms to associate manually gated immune phenotypes with clinical or pre-clinical disease endpoints of interest in a rapid and unbiased manner. Using this approach, we identify discrete immune profiles that correspond with either weight loss or histologic colitis in a T cell transfer model of inflammatory bowel disease (IBD), and show distinct nodes of immune dysregulation in the IBDs, Crohn’s disease and ulcerative colitis. This streamlined informatics approach for cytometry data analysis leverages publicly available software, can be applied to manually or computationally gated cytometry data, is suitable for any clinical or pre-clinical setting, and embraces ultra-high content flow and mass cytometry as a discovery engine. PMID:27669154

  1. Interleukin-19 Downregulates Interleukin-4-Induced Eotaxin Production in Human Nasal Fibroblasts

    Directory of Open Access Journals (Sweden)

    Masaaki Higashino

    2011-01-01

    Conclusions: These results suggest that IL-19 down-regulates IL-4-induced eotaxin production via SOCS-1 in human nasal fibroblasts. In non-hematopoietic cells in AR, IL-19 might be an immunosuppressive factor.

  2. Reverse immunogenetics: from HLA-disease associations to vaccine candidates.

    Science.gov (United States)

    Davenport, M P; Hill, A V

    1996-01-01

    Analysis of the human leukocyte antigens (HLA) in patients with either infectious or autoimmune diseases has led to the identification of several HLA alleles associated with either resistance or susceptibility to disease. Understanding the role of HLA molecules in the presentation of peptide antigens to T cells has led to the use of 'reverse immunogenetics': a novel approach to analysing the key antigenic peptides that are presented by the relevant HLA molecules. Recent advances in the analysis of naturally occurring peptides bound to HLA molecules has allowed the direct identification of antigenic peptides from living cells and has supported the development of vaccine candidates, such as the liver-stage antigen 1 in malaria.

  3. Regulation of disease-associated gene expression in the 3D genome.

    Science.gov (United States)

    Krijger, Peter Hugo Lodewijk; de Laat, Wouter

    2016-12-01

    Genetic variation associated with disease often appears in non-coding parts of the genome. Understanding the mechanisms by which this phenomenon leads to disease is necessary to translate results from genetic association studies to the clinic. Assigning function to this type of variation is notoriously difficult because the human genome harbours a complex regulatory landscape with a dizzying array of transcriptional regulatory sequences, such as enhancers that have unpredictable, promiscuous and context-dependent behaviour. In this Review, we discuss how technological advances have provided increasingly detailed information on genome folding; for example, genome folding forms loops that bring enhancers and target genes into close proximity. We also now know that enhancers function within topologically associated domains, which are structural and functional units of chromosomes. Studying disease-associated mutations and chromosomal rearrangements in the context of the 3D genome will enable the identification of dysregulated target genes and aid the progression from descriptive genetic association results to discovering molecular mechanisms underlying disease.

  4. Inhaled Pollutants: The Molecular Scene behind Respiratory and Systemic Diseases Associated with Ultrafine Particulate Matter

    Directory of Open Access Journals (Sweden)

    Hussein Traboulsi

    2017-01-01

    Full Text Available Air pollution of anthropogenic origin is largely from the combustion of biomass (e.g., wood, fossil fuels (e.g., cars and trucks, incinerators, landfills, agricultural activities and tobacco smoke. Air pollution is a complex mixture that varies in space and time, and contains hundreds of compounds including volatile organic compounds (e.g., benzene, metals, sulphur and nitrogen oxides, ozone and particulate matter (PM. PM0.1 (ultrafine particles (UFP, those particles with a diameter less than 100 nm (includes nanoparticles (NP are considered especially dangerous to human health and may contribute significantly to the development of numerous respiratory and cardiovascular diseases such as chronic obstructive pulmonary disease (COPD and atherosclerosis. Some of the pathogenic mechanisms through which PM0.1 may contribute to chronic disease is their ability to induce inflammation, oxidative stress and cell death by molecular mechanisms that include transcription factors such as nuclear factor κB (NF-κB and nuclear factor (erythroid-derived 2-like 2 (Nrf2. Epigenetic mechanisms including non-coding RNA (ncRNA may also contribute towards the development of chronic disease associated with exposure to PM0.1. This paper highlights emerging molecular concepts associated with inhalational exposure to PM0.1 and their ability to contribute to chronic respiratory and systemic disease.

  5. Inhaled Pollutants: The Molecular Scene behind Respiratory and Systemic Diseases Associated with Ultrafine Particulate Matter

    Science.gov (United States)

    Traboulsi, Hussein; Guerrina, Necola; Iu, Matthew; Maysinger, Dusica; Ariya, Parisa; Baglole, Carolyn J.

    2017-01-01

    Air pollution of anthropogenic origin is largely from the combustion of biomass (e.g., wood), fossil fuels (e.g., cars and trucks), incinerators, landfills, agricultural activities and tobacco smoke. Air pollution is a complex mixture that varies in space and time, and contains hundreds of compounds including volatile organic compounds (e.g., benzene), metals, sulphur and nitrogen oxides, ozone and particulate matter (PM). PM0.1 (ultrafine particles (UFP)), those particles with a diameter less than 100 nm (includes nanoparticles (NP)) are considered especially dangerous to human health and may contribute significantly to the development of numerous respiratory and cardiovascular diseases such as chronic obstructive pulmonary disease (COPD) and atherosclerosis. Some of the pathogenic mechanisms through which PM0.1 may contribute to chronic disease is their ability to induce inflammation, oxidative stress and cell death by molecular mechanisms that include transcription factors such as nuclear factor κB (NF-κB) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Epigenetic mechanisms including non-coding RNA (ncRNA) may also contribute towards the development of chronic disease associated with exposure to PM0.1. This paper highlights emerging molecular concepts associated with inhalational exposure to PM0.1 and their ability to contribute to chronic respiratory and systemic disease. PMID:28125025

  6. A network based method for analysis of lncRNA-disease associations and prediction of lncRNAs implicated in diseases.

    Science.gov (United States)

    Yang, Xiaofei; Gao, Lin; Guo, Xingli; Shi, Xinghua; Wu, Hao; Song, Fei; Wang, Bingbo

    2014-01-01

    Increasing evidence has indicated that long non-coding RNAs (lncRNAs) are implicated in and associated with many complex human diseases. Despite of the accumulation of lncRNA-disease associations, only a few studies had studied the roles of these associations in pathogenesis. In this paper, we investigated lncRNA-disease associations from a network view to understand the contribution of these lncRNAs to complex diseases. Specifically, we studied both the properties of the diseases in which the lncRNAs were implicated, and that of the lncRNAs associated with complex diseases. Regarding the fact that protein coding genes and lncRNAs are involved in human diseases, we constructed a coding-non-coding gene-disease bipartite network based on known associations between diseases and disease-causing genes. We then applied a propagation algorithm to uncover the hidden lncRNA-disease associations in this network. The algorithm was evaluated by leave-one-out cross validation on 103 diseases in which at least two genes were known to be involved, and achieved an AUC of 0.7881. Our algorithm successfully predicted 768 potential lncRNA-disease associations between 66 lncRNAs and 193 diseases. Furthermore, our results for Alzheimer's disease, pancreatic cancer, and gastric cancer were verified by other independent studies.

  7. Impact of natural salt powder inhalation treatment in asthmatic mice to the pathological changes of lung and blood serum levels of IL-4,IL-5 and IL-13%矿盐粉粒吸入疗法对哮喘小鼠肺组织病理形态及血清IL-4、IL-5、IL-13水平的影响

    Institute of Scientific and Technical Information of China (English)

    范利娟; 许华君; 吴占敖; 端礼荣

    2012-01-01

    目的:探讨天然矿盐粉粒吸入对哮喘小鼠肺组织病理及血清IL-4、IL-5、IL-13水平的影响.方法:将40只Balb/c雌性小鼠随机分为对照组、模型组、30 min治疗组、60 min治疗组,每组10只.第0、7天分别在模型组、30 min治疗组、60 min治疗组小鼠腹腔注射致敏液鸡卵清蛋白(Ovalbumin,OVA),对照组注射生理盐水.第14天对模型组和治疗组行超声雾化吸入OVA以诱发哮喘;对照组则以生理盐水雾化吸入.第15天起,两治疗组每天分别用矿盐粉粒吸入治疗30 min或60 min,对照组和模型组则吸入空气,各组共吸入10 d.第22至第24天连续诱发哮喘3天,第25天处死小鼠,取肺组织常规行病理切片,ELISA法检测血清IL-4、IL-5、IL-13水平.结果:与对照组比较,模型组小鼠肺组织病理出现支气管收缩、管腔狭窄、黏膜上皮坏死脱落,大量炎症细胞浸润、嗜酸性粒细胞聚集.与模型组比较,治疗组上述表现明显减轻.与对照组比较,模型组小鼠血清IL-4、IL-5和IL-13含量明显升高(P<0.01或P<0.05);与模型组比较,两治疗组的IL-4、IL-5、IL-13含量则明显降低(P<0.01).结论:吸入天然矿盐粉可减轻支气管哮喘小鼠气道炎症,降低血清中哮喘相关细胞因子IL-4、IL-5、IL-13的含量.%Objective: To investigate the pathological changes of lung and the influence to serum IL-4, IL-5 and IL-13 levels in asthmatic mice treated by salt powder inhalation. Methods: Forty Balb/c female mice were divided randomly into control group, model group, therapy group A, therapy group B with each group of 10 only. On day 0 and 7, the mice of model group, therapy group A and therapy group B were injected intra-peritoneal with liquid sensitized( ovalbumin ), while the mice of control group with saline. On day 14, the mice inhaled the aerosol of 1% ovalbumin to induce asthma for the first time. On day 15 , therapy group A and therapy group B were treated with salt powder

  8. Clinical research of the effect of oral administration of probiotic products among the pregnant women during the third trimester of pregnancy on intestinal flora and levels of IL-4, IFN-γin umbilical cord blood of the neonates%晚孕期孕妇口服益生菌制剂对新生儿肠道菌群及脐血IL-4、IFN-γ水平影响的临床研究

    Institute of Scientific and Technical Information of China (English)

    刘明颖; 李辉; 施展; 金良怡

    2012-01-01

    Objective: To detect the changes of intestinal flora and levels of IL -4, IFN - 7 in umbilical cord blood of the neonates by oral administration of probiotic products among the pregnant women during the third trimester of pregnancy, explore the effect of probiotics on neonatal immunity. Methods: Thirty - four pregnant women who adopted elective cesarean section were divided into experimental group and control group randomly, 21 pregnant women in experimental group were treated with milk powder containing probiotics, while 21 pregnant women in control group were treated with milk powder without probiotics, the neonatal feces were obtained for bacterial culture under aerobic environment and anaerobic environment, respectively, then bacterial smears were performed to observe the changes of intestinal flora of neonates. After cesarean section, the umbilical cord blood samples of neonates were collected, then serum samples were obtained, ELISA was used to detect the levels of IL -4 and IFN - -y in the two groups. Results: There was no significant difference in the changes of intestinal flora of neonates between the two groups ( P > 0. 05 ) ; there was significant difference in umbilical cord serum level of IL - 4 between the two groups ( P 0. 05 ) ; there was significant difference in the ratio of IL - 4/IFN - 7 between the two groups ( P < 0. 05 ). Conclusion: Oral administration of probiotic products among the pregnant women during the third trimester of pregnancy has no obvious impact on the changes of intestinal flora of neonates, but after IL - 4 and IFN - 7 detection in umbilical cord of neonates, it is indicated that oral administration of probiotic products among the pregnant women during the third trimester of pregnancy may enhance neonatal immunity, and prevent or reduce the occurrence of neonatal allergic diseases.%目的:通过给妊娠晚期孕妇服用含有益生菌的孕妇奶粉,检测其新生儿肠道菌群变化及新生儿脐血中IL-4、IFN-γ的

  9. Quantity of IL-2, IL-4, IL-10, INF-γ, TNF-α and KC-like cytokines in serum of bitches with pyometra in different stages of oestrous cycle and pregnancy.

    Science.gov (United States)

    Maciel, G S; Uscategui, R R; de Almeida, V T; Oliveira, M E F; Feliciano, M A R; Vicente, W R R

    2014-08-01

    The occurrence of the pyometra is most common in the first half of the dioestrus when there is decreased cellular immunity associated with increased serum concentration of progesterone in females. The aim of this study was to determine the immunological profile of bitches with pyometra, studying serum levels of IL-2, IL-4, IL-10, IFN-γ, KC-like and TNF-α and comparing them with those of healthy bitches in anoestrus, dioestrus and pregnant. Forty females were divided into four experimental groups: group 1 (G1): with pyometra (n = 10); group 2 (G2): bitches in the second week of gestation (n = 10); group 3 (G3): in anoestrus (n = 10); and group 4 (G4): in dioestrus (n = 10). The serum levels for IL-2, KC-like, INF-γ and TNF-α were similar for all experimental groups. The values obtained for IL-10 were found increased (p < 0.001) in animals in dioestrus and pyometra compared with females in anoestrus and pregnant, and the levels of IL-4 observed were significantly greater (p < 0.001) in bitches with pyometra when compared with others. The cytokine profile in animals with pyometra is similar to bitches in dioestrus for IL-10 and had increase in IL-4 for bitches with pyometra, which represents an anti-inflammatory these cases. This suggests the presence of an immunosuppressive state in both cases, which may explain the propensity of bitches in dioestrus to be affected by pyometra and the severity of the disease on these animals.

  10. Effects of β-d-mannuronic acid, as a novel non-steroidal anti-inflammatory medication within immunosuppressive properties, on IL17, RORγt, IL4 and GATA3 gene expressions in rheumatoid arthritis patients

    Science.gov (United States)

    Barati, Anis; Jamshidi, Ahmad Reza; Ahmadi, Hossein; Aghazadeh, Zahra; Mirshafiey, Abbas

    2017-01-01

    Rheumatoid arthritis (RA) is the most common form of chronic inflammatory arthritis characterized by pain, swelling and destruction of joints, with a resultant disability. Disease-modifying anti-rheumatic drugs (DMARDs) and biological drugs can interfere with the disease process. In this study, the effect of β-d-mannuronic acid (M2000) as a novel non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive and anti-inflammatory effects together with antioxidant effects was evaluated on IL17, RORγt, IL4 and GATA3 gene expression in 12 RA patients. Previously, M2000 driven from sodium alginate (natural product; patented, DEU: 102016113018.4) has shown a notable efficacy in experimental models of multiple sclerosis, RA and nephrotic syndrome. This study was performed on 12 patients with RA who had an inadequate response to conventional treatments. During this trial, patients were permitted to continue the conventional therapy excluding NSAIDs. M2000 was administered orally at a dose of 500 mg twice daily for 12 weeks. The peripheral blood mononuclear cells (PBMCs) were collected before and after treatment to evaluate the expression levels of IL4, GATA3, IL17 and RORγt. The gene expression results showed that M2000 has a potent efficacy, so that it could not only significantly decrease IL17 and RORγt levels but also increase IL4 and GATA3 levels after 12 weeks of treatment. Moreover, the gene expression results were in accordance with the clinical and preclinical assessments. In conclusion, M2000 as a natural novel agent has therapeutic and immunosuppressive properties on RA patients (identifier: IRCT2014011213739N2).

  11. Zoonotic diseases associated with free-roaming cats.

    Science.gov (United States)

    Gerhold, R W; Jessup, D A

    2013-05-01

    Free-roaming cat populations have been identified as a significant public health threat and are a source for several zoonotic diseases including rabies, toxoplasmosis, cutaneous larval migrans because of various nematode parasites, plague, tularemia and murine typhus. Several of these diseases are reported to cause mortality in humans and can cause other important health issues including abortion, blindness, pruritic skin rashes and other various symptoms. A recent case of rabies in a young girl from California that likely was transmitted by a free-roaming cat underscores that free-roaming cats can be a source of zoonotic diseases. Increased attention has been placed on trap-neuter-release (TNR) programmes as a viable tool to manage cat populations. However, some studies have shown that TNR leads to increased immigration of unneutered cats into neutered populations as well as increased kitten survival in neutered groups. These compensatory mechanisms in neutered groups leading to increased kitten survival and immigration would confound rabies vaccination campaigns and produce naïve populations of cats that can serve as source of zoonotic disease agents owing to lack of immunity. This manuscript is a review of the various diseases of free-roaming cats and the public health implications associated with the cat populations.

  12. Intestinal invasion and disseminated disease associated with Penicillium chrysogenum

    Directory of Open Access Journals (Sweden)

    Herchline Thomas E

    2005-12-01

    Full Text Available Abstract Background Penicillium sp., other than P. marneffei, is an unusual cause of invasive disease. These organisms are often identified in immunosuppressed patients, either due to human immunodeficiency virus or from immunosuppressant medications post-transplantation. They are a rarely identified cause of infection in immunocompetent hosts. Case presentation A 51 year old African-American female presented with an acute abdomen and underwent an exploratory laparotomy which revealed an incarcerated peristomal hernia. Her postoperative course was complicated by severe sepsis syndrome with respiratory failure, hypotension, leukocytosis, and DIC. On postoperative day 9 she was found to have an anastamotic breakdown. Pathology from the second surgery showed transmural ischemic necrosis with angioinvasion of a fungal organism. Fungal blood cultures were positive for Penicillium chrysogenum and the patient completed a 6 week course of amphotericin B lipid complex, followed by an extended course oral intraconazole. She was discharged to a nursing home without evidence of recurrent infection. Discussion Penicillium chrysogenum is a rare cause of infection in immunocompetent patients. Diagnosis can be difficult, but Penicillium sp. grows rapidly on routine fungal cultures. Prognosis remains very poor, but aggressive treatment is essential, including surgical debridement and the removal of foci of infection along with the use of amphotericin B. The clinical utility of newer antifungal agents remains to be determined.

  13. Ribosome profiling reveals features of normal and disease-associated mitochondrial translation

    NARCIS (Netherlands)

    Rooijers, K.; Loayza-Puch, F.; Nijtmans, L.G.J.; Agami, R.

    2013-01-01

    Mitochondria are essential cellular organelles for generation of energy and their dysfunction may cause diabetes, Parkinson's disease and multi-systemic failure marked by failure to thrive, gastrointestinal problems, lactic acidosis and early lethality. Disease-associated mitochondrial mutations oft

  14. Ribosome profiling reveals features of normal and disease-associated mitochondrial translation

    NARCIS (Netherlands)

    Rooijers, K.; Loayza-Puch, F.; Nijtmans, L.G.J.; Agami, R.

    2013-01-01

    Mitochondria are essential cellular organelles for generation of energy and their dysfunction may cause diabetes, Parkinson's disease and multi-systemic failure marked by failure to thrive, gastrointestinal problems, lactic acidosis and early lethality. Disease-associated mitochondrial mutations oft

  15. Inhibitory effects of rat bone marrow-derived dendritic cells on naïve and alloantigen-specific CD4+ T cells: a comparison between dendritic cells generated with GM-CSF plus IL-4 and dendritic cells generated with GM-CSF plus IL-10

    Directory of Open Access Journals (Sweden)

    Ulrichs Karin

    2009-01-01

    Full Text Available Abstract Background Unlike mouse immature bone marrow (BM-derived dendritic cells (DC, rat immature BMDC have not been thoroughly characterised in vitro for the mechanisms underlying their suppressive effect. To better characterise these mechanisms we therefore analysed the phenotypes and immune inhibitory properties of rat BMDC generated with GM-CSF plus IL-4 (= IL-4 DC and with GM-CSF plus IL-10 (= IL-10 DC. Results Both IL-4 DC and IL-10 DC exhibited lower surface expression of MHC class II and costimulatory molecules than mature splenic DC. They had a strong inhibitory effect on responsive T cells in vitro and despite their weak function as antigen-presenting cells they induced anergic T cells. However, only anergic T cells induced by IL-4 DC had a suppressive effect on responsive T cells. Induction of suppressive/tolerogenic T cells by IL-4 DC required direct contact between antigen-specific T cells and IL-4 DC. In addition, IL-4 DC and IL-10 DC prolonged allograft survival in an antigen-specific manner. Conclusion A unique phenotype of immature BMDC was isolated from the cultures. The mechanisms underlying the suppressive effect may be caused by their inability to deliver adequate costimulatory signals for T-cell activation. In addition, IL-4 DC but not IL-10 DC induce anergic T cells with suppressive function. This indicates that IL-4 DC and IL-10 DC may differ in the quality of their costimulation although no differences in the surface expression of costimulatory molecules were found.

  16. A novel prion disease associated with diarrhea and autonomic neuropathy.

    Science.gov (United States)

    Mead, Simon; Gandhi, Sonia; Beck, Jon; Caine, Diana; Gallujipali, Dillip; Carswell, Christopher; Hyare, Harpreet; Joiner, Susan; Ayling, Hilary; Lashley, Tammaryn; Linehan, Jacqueline M; Al-Doujaily, Huda; Sharps, Bernadette; Revesz, Tamas; Sandberg, Malin K; Reilly, Mary M; Koltzenburg, Martin; Forbes, Alastair; Rudge, Peter; Brandner, Sebastian; Warren, Jason D; Wadsworth, Jonathan D F; Wood, Nicholas W; Holton, Janice L; Collinge, John

    2013-11-14

    Human prion diseases, although variable in clinicopathological phenotype, generally present as neurologic or neuropsychiatric conditions associated with rapid multifocal central nervous system degeneration that is usually dominated by dementia and cerebellar ataxia. Approximately 15% of cases of recognized prion disease are inherited and associated with coding mutations in the gene encoding prion protein (PRNP). The availability of genetic diagnosis has led to a progressive broadening of the recognized spectrum of disease. We used longitudinal clinical assessments over a period of 20 years at one hospital combined with genealogical, neuropsychological, neurophysiological, neuroimaging, pathological, molecular genetic, and biochemical studies, as well as studies of animal transmission, to characterize a novel prion disease in a large British kindred. We studied 6 of 11 affected family members in detail, along with autopsy or biopsy samples obtained from 5 family members. We identified a PRNP Y163X truncation mutation and describe a distinct and consistent phenotype of chronic diarrhea with autonomic failure and a length-dependent axonal, predominantly sensory, peripheral polyneuropathy with an onset in early adulthood. Cognitive decline and seizures occurred when the patients were in their 40s or 50s. The deposition of prion protein amyloid was seen throughout peripheral organs, including the bowel and peripheral nerves. Neuropathological examination during end-stage disease showed the deposition of prion protein in the form of frequent cortical amyloid plaques, cerebral amyloid angiopathy, and tauopathy. A unique pattern of abnormal prion protein fragments was seen in brain tissue. Transmission studies in laboratory mice were negative. Abnormal forms of prion protein that were found in multiple peripheral tissues were associated with diarrhea, autonomic failure, and neuropathy. (Funded by the U.K. Medical Research Council and others.).

  17. Transposable elements in disease-associated cryptic exons.

    Science.gov (United States)

    Vorechovsky, Igor

    2010-02-01

    Transposable elements (TEs) make up a half of the human genome, but the extent of their contribution to cryptic exon activation that results in genetic disease is unknown. Here, a comprehensive survey of 78 mutation-induced cryptic exons previously identified in 51 disease genes revealed the presence of TEs in 40 cases (51%). Most TE-containing exons were derived from short interspersed nuclear elements (SINEs), with Alus and mammalian interspersed repeats (MIRs) covering >18 and >16% of the exonized sequences, respectively. The majority of SINE-derived cryptic exons had splice sites at the same positions of the Alu/MIR consensus as existing SINE exons and their inclusion in the mRNA was facilitated by phylogenetically conserved changes that improved both traditional and auxiliary splicing signals, thus marking intronic TEs amenable for pathogenic exonization. The overrepresentation of MIRs among TE exons is likely to result from their high average exon inclusion levels, which reflect their strong splice sites, a lack of splicing silencers and a high density of enhancers, particularly (G)AA(G) motifs. These elements were markedly depleted in antisense Alu exons, had the most prominent position on the exon-intron gradient scale and are proposed to promote exon definition through enhanced tertiary RNA interactions involving unpaired (di)adenosines. The identification of common mechanisms by which the most dynamic parts of the genome contribute both to new exon creation and genetic disease will facilitate detection of intronic mutations and the development of computational tools that predict TE hot-spots of cryptic exon activation.

  18. Economic Burden of Disease-Associated Malnutrition at the State Level

    Science.gov (United States)

    Goates, Scott; Du, Kristy; Braunschweig, Carol A.; Arensberg, Mary Beth

    2016-01-01

    Background Disease-associated malnutrition has been identified as a prevalent condition, particularly for the elderly, which has often been overlooked in the U.S. healthcare system. The state-level burden of community-based disease-associated malnutrition is unknown and there have been limited efforts by state policy makers to identify, quantify, and address malnutrition. The objective of this study was to examine and quantify the state-level economic burden of disease-associated malnutrition. Methods Direct medical costs of disease-associated malnutrition were calculated for 8 diseases: Stroke, Chronic Obstructive Pulmonary Disease, Coronary Heart Failure, Breast Cancer, Dementia, Musculoskeletal Disorders, Depression, and Colorectal Cancer. National disease and malnutrition prevalence rates were estimated for subgroups defined by age, race, and sex using the National Health and Nutrition Examination Survey and the National Health Interview Survey. State prevalence of disease-associated malnutrition was estimated by combining national prevalence estimates with states’ demographic data from the U.S. Census. Direct medical cost for each state was estimated as the increased expenditures incurred as a result of malnutrition. Principal Findings Direct medical costs attributable to disease-associated malnutrition vary among states from an annual cost of $36 per capita in Utah to $65 per capita in Washington, D.C. Nationally the annual cost of disease-associated malnutrition is over $15.5 billion. The elderly bear a disproportionate share of this cost on both the state and national level. Conclusions Additional action is needed to reduce the economic impact of disease-associated malnutrition, particularly at the state level. Nutrition may be a cost-effective way to help address high health care costs. PMID:27655372

  19. HDL-S1P: cardiovascular functions, disease-associated alterations, and therapeutic applications.

    Science.gov (United States)

    Levkau, Bodo

    2015-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid contained in High-density lipoproteins (HDL) and has drawn considerable attention in the lipoprotein field as numerous studies have demonstrated its contribution to several functions inherent to HDL. Some of them are partly and some entirely due to the S1P contained in HDL (HDL-S1P). Despite the presence of over 1000 different lipids in HDL, S1P stands out as it possesses its own cell surface receptors through which it exercises key physiological functions. Most of the S1P in human plasma is associated with HDL, and the amount of HDL-S1P influences the quality and quantity of HDL-dependent functions. The main binding partner of S1P in HDL is apolipoprotein M but others may also exist particularly under conditions of acute S1P elevations. HDL not only exercise functions through their S1P content but have also an impact on genuine S1P signaling by influencing S1P bioactivity and receptor presentation. HDL-S1P content is altered in human diseases such as atherosclerosis, coronary artery disease, myocardial infarction, renal insufficiency and diabetes mellitus. Low HDL-S1P has also been linked to impaired HDL functions associated with these disorders. Although the pathophysiological and molecular reasons for such disease-associated shifts in HDL-S1P are little understood, there have been successful approaches to circumvent their adverse implications by pharmacologically increasing HDL-S1P as means to improve HDL function. This mini-review will cover the current understanding of the contribution of HDL-S1P to physiological HDL function, its alteration in disease and ways for its restoration to correct HDL dysfunction.

  20. HDL-S1P: cardiovascular functions, disease-associated alterations, and therapeutic applications

    Science.gov (United States)

    Levkau, Bodo

    2015-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid contained in High-density lipoproteins (HDL) and has drawn considerable attention in the lipoprotein field as numerous studies have demonstrated its contribution to several functions inherent to HDL. Some of them are partly and some entirely due to the S1P contained in HDL (HDL-S1P). Despite the presence of over 1000 different lipids in HDL, S1P stands out as it possesses its own cell surface receptors through which it exercises key physiological functions. Most of the S1P in human plasma is associated with HDL, and the amount of HDL-S1P influences the quality and quantity of HDL-dependent functions. The main binding partner of S1P in HDL is apolipoprotein M but others may also exist particularly under conditions of acute S1P elevations. HDL not only exercise functions through their S1P content but have also an impact on genuine S1P signaling by influencing S1P bioactivity and receptor presentation. HDL-S1P content is altered in human diseases such as atherosclerosis, coronary artery disease, myocardial infarction, renal insufficiency and diabetes mellitus. Low HDL-S1P has also been linked to impaired HDL functions associated with these disorders. Although the pathophysiological and molecular reasons for such disease-associated shifts in HDL-S1P are little understood, there have been successful approaches to circumvent their adverse implications by pharmacologically increasing HDL-S1P as means to improve HDL function. This mini-review will cover the current understanding of the contribution of HDL-S1P to physiological HDL function, its alteration in disease and ways for its restoration to correct HDL dysfunction. PMID:26539121

  1. 特应质对呼吸道合胞病毒毛细支气管炎患儿鼻咽吸出物IL-4和IL-12及干扰素-γ水平的影响%Effect of Atopy on the IL-4,IL-12 and IFN-γ Levels in NPS of Respiratory Syncytial Virus Bronchiolitis in Infancy

    Institute of Scientific and Technical Information of China (English)

    姚欢银; 王伟; 王小仙; 刘淑梅; 陈啸洪

    2011-01-01

    Objective To study the effect of Atopy on the changes of IL - 4, IL - 12 and IFN - γ levels in NPS of respiratory syncytial virus bronchiolitis in infancy. Methods 49 infants with Bronchiolitis admitted from November 2008 to February 2009 were involved, with 30 cases in RSV positive group, 19 cases in RSV negative group and 23 cases in control group. The RSV positive group was further divided into atopy positive group (18 cases ) and atopy negative group (12 cases ) according to clinical features. The levels of IL-4, IL-12 and IFN-γ in NPS of each group were detected by ELISA technique. Results The level of IL -4 was significantly higher in group of RSV Bronchiolitis at acute stage [ ( 7. 0 ±4. 2 ) ng/L ] than RSV - negative Bronchiolitis group [ ( 4. 9 ± 2. 1 ) ng/L ] and control group [ ( 3. 7 ± 2. 1 ) ng/L ]; However, the level of IFN-γ in the group of RSV Bronchiolitis at acute stage [ ( 135. 3 ± 80. 7 ) ng/L ] was significantly lower than the RSV - Bronchiolitis group [ ( 277. 9 ± 100. 8 ) ng/L ] and control group [ ( 252. 7 ± 80. 2 ) ng/L ] ( P < 0. 01 ); IL - 12 levels in NPS was significantly higher in RSV - negative Bronchiolitis group [ ( 1214. 5 ± 871. 3 ) ng/L ] than RSV positive Bronchiolitis group [ ( 475. 1 ± 254. 0 ) ng/L ] and the control group [ ( 522. 7 ± 166. 6 ) ng/L ] ( P < 0. 01 ). IL-4 level was significantly higher in atopy positive RSV Bronchiolitis infected infants' NPS [ ( 9. 6 ± 3. 1 ) ng/L ] than in atopy negative infants [ ( 3. 1 ± 1. 5 ) ng/L ] and the control group [ ( 3. 7 ± 1. 5 ) ng/L ] ( P <0. 01 ). While the IL - 12 level in atopy positive RSV Bronchiolitis [ ( 341. 7 ± 132. 9 ) ng/L ] was significantly lower ( P <0. 05 ) than the RSV negative Bronchiolitis group [ ( 675. 2 ± 264. 6 ) ng/L ]. IFN-γ level of atopy positive group [ ( 153. 9 ± 95. 9 ) ng/L ] showed no significantly difference ( P >0. 05 ) compared with that of atopy negative group [ ( 107. 4 ± 39. 3 ) ng/L ] ( P > 0. 05

  2. 地氯雷他定片与匹多莫德片联合治疗慢性荨麻疹的临床疗效及对血清IL-2及IL-4水平的影响%Clinical Curative Effect of Desloratadine Combined with Pidotimod in Treatment of Chronic Urticaria and its Influence on serum IL-2 and IL-4 Levels

    Institute of Scientific and Technical Information of China (English)

    丁黎; 杨景煜; 郝雁杰; 郭静; 徐平

    2016-01-01

    目的:观察地氯雷他定片联合匹多莫德片治疗慢性荨麻疹的临床疗效,及治疗前后患者血清IL-2及II-4水平的变化.方法:将2014年6月-2015年7月我院收治的112例慢性荨麻疹患者随机分成两组各56例,其中治疗组给予口服地氯雷他定片与匹多莫德片治疗,对照组单独口服地氯雷他定片治疗;治疗4周后对比两组临床疗效,并测定两组患者治疗前后血清IL-2及IL-4水平.结果:治疗4周后,治疗组治疗总有效率为92.86%,明显高于对照组82.14%,差异具有统计学意义(P<0.05);两组患者治疗后血清IL-2水平升高,IL-4水平降低,且治疗组改变相比对照组更显著,差异均有统计学意义(P<0.05).结论:地氯雷他定片联合匹多莫德片治疗慢性荨麻疹疗效显著,其机制可能与提高血清IL-2水平及降低IL-4水平有关.

  3. AT-RvD1 Modulates CCL-2 and CXCL-8 Production and NF-κB, STAT-6, SOCS1, and SOCS3 Expression on Bronchial Epithelial Cells Stimulated with IL-4

    Directory of Open Access Journals (Sweden)

    Jhony Robison de Oliveira

    2015-01-01

    Full Text Available Bronchial epithelial cells represent the first line of defense against microorganisms and allergens in the airways and play an important role in chronic inflammatory processes such as asthma. In an experimental model, both RvD1 and AT-RvD1, lipid mediators of inflammation resolution, ameliorated some of the most important phenotypes of experimental asthma. Here, we extend these results and demonstrate the effect of AT-RvD1 on bronchial epithelial cells (BEAS-2B stimulated with IL-4. AT-RvD1 (100 nM decreased both CCL2 and CXCL-8 production, in part by decreasing STAT6 and NF-κB pathways. Furthermore, the effects of AT-RvD1 were ALX/FRP2 receptor dependent, as the antagonist of this receptor (BOC1 reversed the inhibition of these chemokines by AT-RvD1. In addition, AT-RvD1 decreased SOCS1 and increased SOCS3 expression, which play important roles in Th1 and Th17 modulation, respectively. In conclusion, AT-RvD1 demonstrated significant effects on the IL-4-induced activation of bronchial epithelial cells and consequently the potential to modulate neutrophilic and eosinophilic airway inflammation in asthma. Taken together, these findings identify AT-RvD1 as a potential proresolving therapeutic agent for allergic responses in the airways.

  4. Development of a new protocol for 2-day generation of mature dendritic cells from human monocytes

    OpenAIRE

    Obermaier Bianca; Dauer Marc; Herten Jan; Schad Katharina; Endres Stefan; Eigler Andreas

    2003-01-01

    We developed a new 2-day protocol for the generation of dendritic cells (DCs) from human monocytes in vitro. First, we demonstrated that 24 hours of culture with GM-CSF and IL-4 are sufficient to generate immature DCs capable of antigen uptake. We then compared two different strategies for DC maturation: proinflammatory mediators were either added together with GM-CSF and IL-4 from the beginning of cell culture or added after 24 hours of differentiation with GM-CSF and IL-4. After 48 hours of...

  5. Hierarchical IL-5 expression defines a subpopulation of highly differentiated human Th2 cells‡

    OpenAIRE

    Upadhyaya, Bhaskar; Yin, Yuzhi; Brenna J Hill; Douek, Daniel C.; Prussin, Calman

    2011-01-01

    Each of the three Th2 cytokine genes, IL-4, IL-5, and IL-13, has different functions. We hypothesized that Th2 heterogeneity could yield Th2 subpopulations with different cytokine expression and effector functions. Using multiple approaches we demonstrate that human Th2 cells are composed of two major subpopulations: a minority IL-5+ (IL-5+, IL-4+, IL-13+) and majority IL-5− Th2 (IL-5−, IL-4+, IL-13+) population. IL-5+ Th2 cells comprised only 20% of all Th2 cells.Serial rounds of in vitro di...

  6. Prediction of MicroRNA-Disease Associations Based on Social Network Analysis Methods

    Directory of Open Access Journals (Sweden)

    Quan Zou

    2015-01-01

    Full Text Available MicroRNAs constitute an important class of noncoding, single-stranded, ~22 nucleotide long RNA molecules encoded by endogenous genes. They play an important role in regulating gene transcription and the regulation of normal development. MicroRNAs can be associated with disease; however, only a few microRNA-disease associations have been confirmed by traditional experimental approaches. We introduce two methods to predict microRNA-disease association. The first method, KATZ, focuses on integrating the social network analysis method with machine learning and is based on networks derived from known microRNA-disease associations, disease-disease associations, and microRNA-microRNA associations. The other method, CATAPULT, is a supervised machine learning method. We applied the two methods to 242 known microRNA-disease associations and evaluated their performance using leave-one-out cross-validation and 3-fold cross-validation. Experiments proved that our methods outperformed the state-of-the-art methods.

  7. STAT6 Mediates Interleukin-4 Growth Inhibition in Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Jennifer L. Gooch

    2002-01-01

    Full Text Available In addition to acting as a hematopoietic growth factor, interleukin-4 (IL-4 inhibits growth of some transformed cells in vitro and in vivo. In this study, we show that insulin receptor substrate (IRS-1, IRS-2, and signal transducer and activator of transcription 6 (STAT6 are phosphorylated following IL-4 treatment in MCF-7 breast cancer cells. STAT6 DNA binding is enhanced by IL-4 treatment. STAT6 activation occurs even after IRS-1 depletion, suggesting the two pathways are independent. To examine the role of STAT6 in IL-4-mediated growth inhibition and apoptosis, a fulllength STAT6 cDNA was transfected into MCF-7 cells. Transient overexpression of STAT6 resulted in both cytoplasmic and nuclear expression of the protein, increased DNA binding in response to IL-4, and increased transactivation of an IL-4 responsive promoter. In STAT6-transfected cells, basal proliferation was reduced whereas apoptosis was increased. Finally, stable expression of STAT6 resulted in reduced foci formation compared to vector-transfected cells alone. These results suggest STAT6 is required for IL-4mediated growth inhibition and induction of apoptosis in human breast cancer cells.

  8. Optimisation of the CT h4S bioassay for detection of human interleukin-4 secreted by mononuclear cells stimulated by phytohaemaglutinin or by human leukocyte antigen mismatched mixed lymphocyte culture

    DEFF Research Database (Denmark)

    Petersen, Søren Lykke; Russell, Charlotte Astrid; Bendtzen, Klaus;

    2002-01-01

    bioassay with regards to specificity, sensitivity, detection limit, and reproducibility. We have found the optimal assay conditions to be 1 x 10 (4) CT.h4S cells/well deprived of IL-4 for 24 h and preincubated for 7 h followed by 18 h of incubation with tritiated methyl-thymidine. In this setting the CT.h4......S bioassay detects 5 pg/ml of human recombinant IL-4 with no detection of IL-2 in concentrations below 500 pg/ml. We have found 72 h of culture optimal for detection of IL-2 and IL-4 produced by human mononuclear cells (MNC) in response to stimulation with phytohaemaglutinin and for detection of IL...... of IL-4 detection was not due to high amounts of soluble IL-4 receptor. With the use of 1x10(6) responder cells/well in HLA-mismatched MLC, we found limited IL-4 accumulation still increasing at day 12. We conclude that the CT.h4S bioassay is a reliable and specific method for quantification of IL-4...

  9. Effects of β-D-mannuronic acid, as a novel non-steroidal anti-inflammatory medication within immunosuppressive properties, on IL17, RORγt, IL4 and GATA3 gene expressions in rheumatoid arthritis patients

    Directory of Open Access Journals (Sweden)

    Barati A

    2017-03-01

    Full Text Available Anis Barati,1 Ahmad Reza Jamshidi,2,* Hossein Ahmadi,1 Zahra Aghazadeh,1 Abbas Mirshafiey1,* 1Department of Immunology, School of Public Health, 2Iranian Institute for Health Sciences Research, Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran *These authors contributed equally to this work Abstract: Rheumatoid arthritis (RA is the most common form of chronic inflammatory arthritis characterized by pain, swelling and destruction of joints, with a resultant disability. Disease-modifying anti-rheumatic drugs (DMARDs and biological drugs can interfere with the disease process. In this study, the effect of β-D-mannuronic acid (M2000 as a novel non-steroidal anti-inflammatory drug (NSAID with immunosuppressive and anti-inflammatory effects together with antioxidant effects was evaluated on IL17, RORγt, IL4 and GATA3 gene expression in 12 RA patients. Previously, M2000 driven from sodium alginate (natural product; patented, DEU: 102016113018.4 has shown a notable efficacy in experimental models of multiple sclerosis, RA and nephrotic syndrome. This study was performed on 12 patients with RA who had an inadequate response to conventional treatments. During this trial, patients were permitted to continue the conventional therapy excluding NSAIDs. M2000 was administered orally at a dose of 500 mg twice daily for 12 weeks. The peripheral blood mononuclear cells (PBMCs were collected before and after treatment to evaluate the expression levels of IL4, GATA3, IL17 and RORγt. The gene expression results showed that M2000 has a potent efficacy, so that it could not only significantly decrease IL17 and RORγt levels but also increase IL4 and GATA3 levels after 12 weeks of treatment. Moreover, the gene expression results were in accordance with the clinical and preclinical assessments. In conclusion, M2000 as a natural novel agent has therapeutic and immunosuppressive properties on RA patients (identifier

  10. DiMeX: A Text Mining System for Mutation-Disease Association Extraction.

    Science.gov (United States)

    Mahmood, A S M Ashique; Wu, Tsung-Jung; Mazumder, Raja; Vijay-Shanker, K

    2016-01-01

    The number of published articles describing associations between mutations and diseases is increasing at a fast pace. There is a pressing need to gather such mutation-disease associations into public knowledge bases, but manual curation slows down the growth of such databases. We have addressed this problem by developing a text-mining system (DiMeX) to extract mutation to disease associations from publication abstracts. DiMeX consists of a series of natural language processing modules that preprocess input text and apply syntactic and semantic patterns to extract mutation-disease associations. DiMeX achieves high precision and recall with F-scores of 0.88, 0.91 and 0.89 when evaluated on three different datasets for mutation-disease associations. DiMeX includes a separate component that extracts mutation mentions in text and associates them with genes. This component has been also evaluated on different datasets and shown to achieve state-of-the-art performance. The results indicate that our system outperforms the existing mutation-disease association tools, addressing the low precision problems suffered by most approaches. DiMeX was applied on a large set of abstracts from Medline to extract mutation-disease associations, as well as other relevant information including patient/cohort size and population data. The results are stored in a database that can be queried and downloaded at http://biotm.cis.udel.edu/dimex/. We conclude that this high-throughput text-mining approach has the potential to significantly assist researchers and curators to enrich mutation databases.

  11. ADAM19 expression in human nephrogenesis and renal disease : Associations with clinical and structural deterioration

    NARCIS (Netherlands)

    Melenhorst, W. B. W. H.; van den Heuvel, M. C.; Timmer, A.; Huitema, S.; Bulthuis, M.; Timens, W.; van Goor, H.

    2006-01-01

    ADAM19, an enzyme from the ADAM (a disintegrin and metalloproteinase) family, is involved in various cell-cell and cell-matrix interactions. It can cleave epidermal growth factor (EGF)-like growth factors, such as heparin-binding (HB)-EGF and neuregulin (NRG), from the cell membrane. ADAM-mediated E

  12. [The character of the morphological changes of the mucous membrane of the large intestine and the genetic polymorphism of IL-1RA, IL-1B, IL-4 TNFA in patient with irritable bowel syndrome].

    Science.gov (United States)

    Sarsenbaeva, A S; Ivanova, E L; Burmistrova, A L; Drozdov, I V

    2013-01-01

    The aim of this study was to evaluate the presence or absence of a relationship between the variants of the course of IBS and their association with genetic polymorphisms of genes and intergenic interaction of cytokines. The sample consisted of 81 patients, the diagnosis was verified according to the criteria of the Rome III, were isolated psychopathological, morphological complications, extra-intestinal symptoms. Polymorphism genotyping IL-1Ra, IL-b, IL-4, TNFa performed by PCR. Statistical treatment are a non-parametric analysis of multiple comparisons, hierarchical log-linear analysis. It is found out the relation between the clinical variants with morphological changes of the mucous membrane of the large intestine, the association between gender characteristics of patients with IBS is established and with genetic polymorphisms of cytokines.

  13. CD4(+) T cell-mediated protection against a lethal outcome of systemic infection with vesicular stomatitis virus requires CD40 ligand expression, but not IFN-gamma or IL-4

    DEFF Research Database (Denmark)

    Andersen, C; Jensen, T; Nansen, A

    1999-01-01

    wild-type mice, and residual resistance in these mice was almost completely abrogated by depletion of CD8(+) T cells. In keeping with this, mice lacking both MHC class I and class II expression succumbed to the infection, whereas most class II-deficient mice normally survive. Adoptive transfer......To investigate the mechanism(s) whereby T cells protect against a lethal outcome of systemic infection with vesicular stomatitis virus, mice with targeted defects in genes central to T cell function were tested for resistance to i.v. infection with this virus. Our results show that mice lacking...... the capacity to secrete both IFN-gamma and perforin completely resisted disease. Similar results were obtained using IL-4 knockout mice, indicating that neither cell-mediated nor T(h)2-dependent effector systems were required. In contrast, mice deficient in expression of CD40 ligand were more susceptible than...

  14. Moyamoya disease-associated protein mysterin/RNF213 is a novel AAA+ ATPase, which dynamically changes its oligomeric state

    Science.gov (United States)

    Morito, Daisuke; Nishikawa, Kouki; Hoseki, Jun; Kitamura, Akira; Kotani, Yuri; Kiso, Kazumi; Kinjo, Masataka; Fujiyoshi, Yoshinori; Nagata, Kazuhiro

    2014-03-01

    Moyamoya disease is an idiopathic human cerebrovascular disorder that is characterized by progressive stenosis and abnormal collateral vessels. We recently identified mysterin/RNF213 as its first susceptibility gene, which encodes a 591-kDa protein containing enzymatically active P-loop ATPase and ubiquitin ligase domains and is involved in proper vascular development in zebrafish. Here we demonstrate that mysterin further contains two tandem AAA+ ATPase modules and forms huge ring-shaped oligomeric complex. AAA+ ATPases are known to generally mediate various biophysical and mechanical processes with the characteristic ring-shaped structure. Fluorescence correlation spectroscopy and biochemical evaluation suggested that mysterin dynamically changes its oligomeric forms through ATP/ADP binding and hydrolysis cycles. Thus, the moyamoya disease-associated gene product is a unique protein that functions as ubiquitin ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell.

  15. 窄谱中波紫外线联合复方甘草酸苷片治疗手部湿疹的疗效观察及对外周血IFN-γ、IL-4水平的影响%Curative Effect of Treating Hand Eczema by Narrow-band Ultraviolet B Phototherapy Combined with Compound Glycyrrhizin Injection and the Influence on Peripheral Blood IFN-γ and IL-4 Level

    Institute of Scientific and Technical Information of China (English)

    付昱; 魏义花; 张海蓉; 陈智; 杨静

    2013-01-01

    目的:探讨窄谱中波紫外线(NB-UVB)联合复方甘草酸苷片治疗手部湿疹的的疗效及其对外周血疗效观察IFN-γ、IL-4水平的影响.方法:选取手部湿疹患者160例,随机分为观察组与对照组,每组各80例.对照组给予尿素乳膏涂于患处,观察组采用NB-UVB皮损局部照射联合复方甘草酸苷片治疗,均连续治疗4周.治疗前后观察临床表现、EASI评分、血清IFN-γ、IL-4,记录不良反应.结果:治疗后,观察组与对照组总有效率分别为90.00%、72.50% (P<0.05),EASI评分均不同程度的降低(P<0.01或P<0.05),且观察组EASI评分低于对照组(P<0.05);观察组血清IFN-γ水平降低,IL-4升高(P<0.05),且与对照组相应指标比较,差异具有统计学意义(p<0.05).两组均未见明显的不良反应.结论:窄谱中波紫外线联合复方甘草酸苷片治疗手部湿疹具有较高的临床总有效率,改善了手部湿疹的皮损状况,调节了Thl/Th2细胞因子趋于平衡,且具有较高的安全性,对手部湿疹的临床治疗具有一定的指导意义.

  16. BRWLDA: bi-random walks for predicting lncRNA-disease associations.

    Science.gov (United States)

    Yu, Guoxian; Fu, Guangyuan; Lu, Chang; Ren, Yazhou; Wang, Jun

    2017-09-01

    Increasing efforts have been done to figure out the association between lncRNAs and complex diseases. Many computational models construct various lncRNA similarity networks, disease similarity networks, along with known lncRNA-disease associations to infer novel associations. However, most of them neglect the structural difference between lncRNAs network and diseases network, hierarchical relationships between diseases and pattern of newly discovered associations. In this study, we developed a model that performs Bi-Random Walks to predict novel LncRNA-Disease Associations (BRWLDA in short). This model utilizes multiple heterogeneous data to construct the lncRNA functional similarity network, and Disease Ontology to construct a disease network. It then constructs a directed bi-relational network based on these two networks and available lncRNAs-disease associations. Next, it applies bi-random walks on the network to predict potential associations. BRWLDA achieves reliable and better performance than other comparing methods not only on experiment verified associations, but also on the simulated experiments with masked associations. Case studies further demonstrate the feasibility of BRWLDA in identifying new lncRNA-disease associations.

  17. Ribosome profiling reveals features of normal and disease-associated mitochondrial translation

    NARCIS (Netherlands)

    K. Rooijers (Koos); F. Loayza-Puch (Fabricio); L.G.J. Nijtmans (Leo); R. Agami (Reuven)

    2013-01-01

    textabstractMitochondria are essential cellular organelles for generation of energy and their dysfunction may cause diabetes, Parkinson's disease and multi-systemic failure marked by failure to thrive, gastrointestinal problems, lactic acidosis and early lethality. Disease-associated mitochondrial m

  18. Systematic identification of trans eQTLs as putative drivers of known disease associations

    NARCIS (Netherlands)

    Westra, Harm-Jan; Peters, Marjolein J.; Esko, Tonu; Yaghootkar, Hanieh; Schurmann, Claudia; Kettunen, Johannes; Christiansen, Mark W.; Fairfax, Benjamin P.; Schramm, Katharina; Powell, Joseph E.; Zhernakova, Alexandra; Zhernakova, Daria V.; Veldink, Jan H.; Van den Berg, Leonard H.; Karjalainen, Juha; Withoff, Sebo; Uitterlinden, Andre G.; Hofman, Albert; Rivadeneira, Fernando; 't Hoen, Peter A. C.; Reinmaa, Eva; Fischer, Krista; Nelis, Mari; Milani, Lili; Melzer, David; Ferrucci, Luigi; Singleton, Andrew B.; Hernandez, Dena G.; Nalls, Michael A.; Homuth, Georg; Nauck, Matthias; Radke, Doerte; Voelker, Uwe; Perola, Markus; Salomaa, Veikko; Brody, Jennifer; Suchy-Dicey, Astrid; Gharib, Sina A.; Enquobahrie, Daniel A.; Lumley, Thomas; Montgomery, Grant W.; Makino, Seiko; Prokisch, Holger; Herder, Christian; Roden, Michael; Grallert, Harald; Meitinger, Thomas; Strauch, Konstantin; Li, Yang; Jansen, Ritsert C.; Visscher, Peter M.; Knight, Julian C.; Psaty, Bruce M.; Ripatti, Samuli; Teumer, Alexander; Frayling, Timothy M.; Metspalu, Andres; van Meurs, Joyce B. J.; Franke, Lude; Hoen, Peter A.C. ’t

    2013-01-01

    Identifying the downstream effects of disease-associated SNPs is challenging. To help overcome this problem, we performed expression quantitative trait locus (eQTL) meta-analysis in non-transformed peripheral blood samples from 5,311 individuals with replication in 2,775 individuals. We identified

  19. Systematic identification of trans eQTLs as putative drivers of known disease associations

    NARCIS (Netherlands)

    H.J. Westra (Harm-Jan); M.J. Peters (Marjolein); T. Esko (Tõnu); H. Yaghootkar (Hanieh); C. Schurmann (Claudia); J. Kettunen (Johannes); M.W. Christiansen (Mark); B.P. Fairfax (Benjamin); K. Schramm (Katharina); J.E. Powell (Joseph); A. Zhernakova (Alexandra); J.H. Veldink (Jan); L.H. van den Berg (Leonard); J. Karjalainen (Juha); S. Withoff (Sebo); A.G. Uitterlinden (André); B. Hofman; F. Rivadeneira Ramirez (Fernando); P.A.C. 't Hoen (Peter); E. Reinmaa (Eva); K. Fischer (Kathelijn); M. Nelis (Mari); A.L. Milani (Alfredo); D. Melzer (David); L. Ferrucci (Luigi); A.B. Singleton (Andrew); D.G. Hernandez (Dena); M.A. Nalls (Michael); G. Homuth (Georg); M.A. Nauck (Matthias); D. Radke (Dörte); U. Vol̈ker (Uwe); M. Perola (Markus); V. Salomaa (Veikko); J. Brody (Jennifer); A. Suchy-Dicey (Astrid); S.A. Gharib (Sina); D. Enquobahrie; T. Lumley (Thomas); G.W. Montgomery; S. Makino (Seiko); H. Prokisch (Holger); C. Herder (Christian); M. Roden (Michael); H. Grallert (Harald); T. Meitinger (Thomas); K. Strauch (Konstantin); Y. Li (Yunmin); J.R.C. Jansen (Jos); P.M. Visscher (Peter M.); J.C. Knight (Julian); B.M. Psaty (Bruce); S. Ripatti (Samuli); A. Teumer (Alexander); T.M. Frayling (Timothy); A. Metspalu (Andres); J.B.J. van Meurs (Joyce); L. Franke (Lude)

    2013-01-01

    textabstractIdentifying the downstream effects of disease-associated SNPs is challenging. To help overcome this problem, we performed expression quantitative trait locus (eQTL) meta-analysis in non-transformed peripheral blood samples from 5,311 individuals with replication in 2,775 individuals. We

  20. Systematic identification of trans eQTLs as putative drivers of known disease associations

    NARCIS (Netherlands)

    Westra, Harm-Jan; Peters, Marjolein J.; Esko, Tonu; Yaghootkar, Hanieh; Schurmann, Claudia; Kettunen, Johannes; Christiansen, Mark W.; Fairfax, Benjamin P.; Schramm, Katharina; Powell, Joseph E.; Zhernakova, Alexandra; Zhernakova, Daria V.; Veldink, Jan H.; Van den Berg, Leonard H.; Karjalainen, Juha; Withoff, Sebo; Uitterlinden, Andre G.; Hofman, Albert; Rivadeneira, Fernando; 't Hoen, Peter A. C.; Reinmaa, Eva; Fischer, Krista; Nelis, Mari; Milani, Lili; Melzer, David; Ferrucci, Luigi; Singleton, Andrew B.; Hernandez, Dena G.; Nalls, Michael A.; Homuth, Georg; Nauck, Matthias; Radke, Doerte; Voelker, Uwe; Perola, Markus; Salomaa, Veikko; Brody, Jennifer; Suchy-Dicey, Astrid; Gharib, Sina A.; Enquobahrie, Daniel A.; Lumley, Thomas; Montgomery, Grant W.; Makino, Seiko; Prokisch, Holger; Herder, Christian; Roden, Michael; Grallert, Harald; Meitinger, Thomas; Strauch, Konstantin; Li, Yang; Jansen, Ritsert C.; Visscher, Peter M.; Knight, Julian C.; Psaty, Bruce M.; Ripatti, Samuli; Teumer, Alexander; Frayling, Timothy M.; Metspalu, Andres; van Meurs, Joyce B. J.; Franke, Lude; Hoen, Peter A.C. ’t

    2013-01-01

    Identifying the downstream effects of disease-associated SNPs is challenging. To help overcome this problem, we performed expression quantitative trait locus (eQTL) meta-analysis in non-transformed peripheral blood samples from 5,311 individuals with replication in 2,775 individuals. We identified a

  1. 75 FR 54496 - Diseases Associated With Exposure to Certain Herbicide Agents (Hairy Cell Leukemia and Other...

    Science.gov (United States)

    2010-09-08

    ... AFFAIRS 38 CFR Part 3 RIN 2900-AN54 Diseases Associated With Exposure to Certain Herbicide Agents (Hairy Cell Leukemia and Other Chronic B-Cell Leukemias, Parkinson's Disease and Ischemic Heart Disease... adjudication regulations concerning the presumptive service connection for certain diseases based upon the...

  2. IL4 — EDRN Public Portal

    Science.gov (United States)

    From NCBI Gene: The protein encoded by this gene is a pleiotropic cytokine produced by activated T cells. This cytokine is a ligand for interleukin 4 receptor. The interleukin 4 receptor also binds to IL13, which may contribute to many overlapping functions of this cytokine and IL13. STAT6, a signal transducer and activator of transcription, has been shown to play a central role in mediating the immune regulatory signal of this cytokine. This gene, IL3, IL5, IL13, and CSF2 form a cytokine gene cluster on chromosome 5q, with this gene particularly close to IL13. This gene, IL13 and IL5 are found to be regulated coordinately by several long-range regulatory elements in an over 120 kilobase range on the chromosome. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008

  3. STAT6 mediates apoptosis of human coronary arterial endothelial cells by interleukin-13.

    Science.gov (United States)

    Nishimura, Yuki; Nitto, Takeaki; Inoue, Teruo; Node, Koichi

    2008-03-01

    Interleukin (IL)-13 is a cytokine produced by type 2 helper T cells that has pathophysiological roles in allergic inflammation and fibrosis formation. IL-13 shares many functional properties with IL-4, which promotes apoptosis of endothelial cells (ECs). We here investigated the effects of IL-13 on apoptosis using human coronary artery endothelial cells (HCAECs). Assessment by WST-1 assay demonstrated that IL-13 as well as IL-4 significantly inhibited cell growth. IL-13 significantly attenuated the cell viability and induced apoptosis of HCAECs as well. Expression of mRNA for vascular endothelial cell growth factor, which maintains survival of ECs, was significantly diminished by IL-13. The effects of IL-13 and IL-4 were abolished by depletion of STAT6 using RNA interference. These results suggest that IL-13 attenuates EC viability by inducing apoptosis, and that STAT6 plays pivotal roles on IL-13- and IL-4-induced apoptosis in ECs.

  4. A human T-cell line with inducible production of interleukins 5 and 4. A model for studies of gene expression.

    Science.gov (United States)

    Mordvinov, V A; Peroni, S E; De Boer, M L; Kees, U R; Sanderson, C J

    1999-08-31

    The production of interleukin-5 (IL5) and interleukin-4 (IL4) by activated T-cells is important in the pathogenesis of helminth infections and allergy. Human Jurkat cells express IL4 but one of the main factors restricting studies of human IL5 expression has been the lack of human T-cell lines which express significant levels of IL5 in an inducible fashion. We report that the human T-cell leukemia cell line (PER-117), previously shown to produce IL2, also produces IL5 and IL4, and is a useful model for the study of the regulation of IL5 and IL4 gene expression. We show that expression of IL5 and IL4 mRNAs in PER-117 cells is stimulation dependent. IL5 and IL4 reporter constructs are also transiently expressed in these cells in an inducible fashion. IL5 production in the PER-117 cell line can be activated by phorbol 12-myristate 13-acetate alone and further enhanced by calcium ionophore A23187, cyclic adenosine 3', 5'-monophosphate or anti-CD28 antibodies. The conditions used to stimulate the PER-117 cells determined whether IL5 production was inhibited by cyclosporin A or dexamethasone. These data indicate that the PER-117 cell line is a model to study signal transduction and transcriptional activation of the human IL5 gene in human T-cells.

  5. Accessory cells with a veiled morphology and movement pattern generated from monocytes after avoidance of plastic adherence and of NADPH oxidase activation. A comparison with GM-CSF/IL-4-induced monocyte-derived dendritic cells.

    Science.gov (United States)

    Ruwhof, Cindy; Canning, Martha O; Grotenhuis, Kristel; de Wit, Harm J; Florencia, Zenovia Z; de Haan-Meulman, Meeny; Drexhage, Hemmo A

    2002-07-01

    Veiled cells (VC) present in afferent lymph transport antigen from the periphery to the draining lymph nodes. Although VC in lymph form a heterogeneous population, some of the cells clearly belong on morphological grounds to the Langerhans cell (LC)/ dendritic cell (DC) series. Here we show that culturing monocytes for 24 hrs while avoiding plastic adherence (polypropylene tubes) and avoiding the activation of NADPH oxidase (blocking agents) results in the generation of a population of veiled accessory cells. The generated VC were actively moving cells like lymph-borne VC in vivo. The monocyte (mo)-derived VC population existed of CD14(dim/-) and CD14(brighT) cells. Of these the CD14(dim/-) VC were as good in stimulating allogeneic T cell proliferation as immature DC (iDC) obtained after one week of adherent culture of monocytes in granulocyte-macrophage-colony stimulating factor (GM-CSF)/interleukin (IL)-4. This underscores the accessory cell function of the mo-derived CD14(dim/-) VC. Although the CD14(dim/-)VC had a modest expression of the DC-specific marker CD83 and were positive for S100, expression of the DC-specific markers CD1a, Langerin, DC-SIGN, and DC-LAMP were absent. This indicates that the here generated CD14(dim/-) VC can not be considered as classical LC/DC. It was also impossible to turn the CD14(dim/-) mo-derived VC population into typical DC by culture for one week in GM-CSF/IL-4 or LPS. In fact the cells died tinder such circumstances, gaining some macrophage characteristics before dying. The IL-12 production from mo-derived CD14(dim/-) VC was lower, whereas the production of IL-10 was higher as compared to iDC. Consequently the T cells that were stimulated by these mo-derived VC produced less IFN-gamma as compared with T cells stimulated by iDC. Our data indicate that it is possible to rapidly generate a population of CD14(dim/-) veiled accessory cells from monocytes. The marker pattern and cytokine production of these VC indicate that this

  6. Expression profiles of the immune genes CD4, CD8β, IFNγ, IL-4, IL-6 and IL-10 in mitogen-stimulated koala lymphocytes (Phascolarctos cinereus by qRT-PCR

    Directory of Open Access Journals (Sweden)

    Iona E. Maher

    2014-03-01

    Full Text Available Investigation of the immune response of the koala (Phascolarctos cinereus is needed urgently, but has been limited by scarcity of species-specific reagents and methods for this unique and divergent marsupial. Infectious disease is an important threat to wild populations of koalas; the most widespread and important of these is Chlamydial disease, caused by Chlamydia pecorum and Chlamydia pneumoniae. In addition, koala retrovirus (KoRV, which is of 100% prevalence in northern Australia, has been proposed as an important agent of immune suppression that could explain the koala’s susceptibility to disease. The correct balance of T regulatory, T helper 1 (Th1 and Th2 lymphocyte responses are important to an individual’s susceptibility or resistance to chlamydial infection. The ability to study chlamydial or KoRV pathogenesis, effects of environmental stressors on immunity, and the response of koalas to vaccines under development, by examining the koala’s adaptive response to natural infection or in-vitro stimulation, has been limited to date by a paucity of species- specific reagents. In this study we have used cytokine sequences from four marsupial genomes to identify mRNA sequences for key T regulatory, Th1 and Th2 cytokines interleukin 4 (IL-4, interleukin 6 (IL-6, interleukin 10 (IL-10 and interferon gamma (IFNγ along with CD4 and CD8β. The koala sequences used for primer design showed >58% homology with grey short-tailed opossum, >71% with tammar wallaby and 78% with Tasmanian devil amino acid sequences. We report the development of real-time RT-PCR assays to measure the expression of these genes in unstimulated cells and after three common mitogen stimulation protocols (phorbol myristate acetate/ionomycin, phorbol myristate acetate/phytohemagglutinin and concanavalin A. Phorbol myristate acetate/ionomycin was found to be the most effective mitogen to up-regulate the production of IL-4, IL-10 and IFNγ. IL-6 production was not

  7. 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.

  8. Text mining facilitates database curation - extraction of mutation-disease associations from Bio-medical literature.

    Science.gov (United States)

    Ravikumar, Komandur Elayavilli; Wagholikar, Kavishwar B; Li, Dingcheng; Kocher, Jean-Pierre; Liu, Hongfang

    2015-06-06

    Advances in the next generation sequencing technology has accelerated the pace of individualized medicine (IM), which aims to incorporate genetic/genomic information into medicine. One immediate need in interpreting sequencing data is the assembly of information about genetic variants and their corresponding associations with other entities (e.g., diseases or medications). Even with dedicated effort to capture such information in biological databases, much of this information remains 'locked' in the unstructured text of biomedical publications. There is a substantial lag between the publication and the subsequent abstraction of such information into databases. Multiple text mining systems have been developed, but most of them focus on the sentence level association extraction with performance evaluation based on gold standard text annotations specifically prepared for text mining systems. We developed and evaluated a text mining system, MutD, which extracts protein mutation-disease associations from MEDLINE abstracts by incorporating discourse level analysis, using a benchmark data set extracted from curated database records. MutD achieves an F-measure of 64.3% for reconstructing protein mutation disease associations in curated database records. Discourse level analysis component of MutD contributed to a gain of more than 10% in F-measure when compared against the sentence level association extraction. Our error analysis indicates that 23 of the 64 precision errors are true associations that were not captured by database curators and 68 of the 113 recall errors are caused by the absence of associated disease entities in the abstract. After adjusting for the defects in the curated database, the revised F-measure of MutD in association detection reaches 81.5%. Our quantitative analysis reveals that MutD can effectively extract protein mutation disease associations when benchmarking based on curated database records. The analysis also demonstrates that incorporating

  9. Necrolytic acral erythema: a rare skin disease associated with hepatitis C virus infection*

    Science.gov (United States)

    Botelho, Luciane Francisca Fernandes; Enokihara, Milvia Maria Simões e Silva; Enokihara, Mauro Yoshiaki

    2016-01-01

    Necrolytic acral erythema is a rare skin disease associated with hepatitis C virus infection. We report a case of a 31-year-old woman with hepatitis C virus infection and decreased zinc serum level. Physical examination revealed scaly, lichenified plaques, well-demarcated with an erythematous peripheral rim located on the lower limbs. After blood transfusion and oral zinc supplementation the patient presented an improvement of lesions. PMID:27828642

  10. Crohn's Disease Associated with Sweet's Syndrome and Sjögren's Syndrome Treated with Infliximab

    Directory of Open Access Journals (Sweden)

    Erina N. Foster

    2005-01-01

    Full Text Available The association of Crohn's disease (CD and Sweet's syndrome is rare and the presence of Sjögren's syndrome in Crohn's disease is even rarer, with only three reports found in the literature. We describe two cases of Crohn's disease associated with Sweet's syndrome, one of which is the first case of CD and Sweet's concomitantly associated with Sjögren's syndrome. Both cases responded rapidly to Infliximab therapy with complete resolution of the skin lesions.

  11. Reducing the risk of Legionnaires' disease associated with cooling towers

    Energy Technology Data Exchange (ETDEWEB)

    Freije, M.R. [HC Information Resources Inc., Carlsbad, CA (United States)

    2008-08-15

    To reduce the health and legal risks associated with Legionnaires' disease, facility managers should take steps to minimize Legionella bacteria in plumbing systems, open industrial equipment, water features, cooling towers, and other aerosolizing water systems. The risk of Legionnaires' disease associated with cooling towers can be reduced by controlling Legionella bacteria in cooling water and preventing transmission of the bacteria from towers to people. This paper presents nine reasonable ways to accomplish these goals. (orig.)

  12. Effective diagnosis of genetic disease by computational phenotype analysis of the disease-associated genome

    OpenAIRE

    Zemojtel, T.; Koehler, S; Mackenroth, L; Jaeger, M.; Hecht, J.; Krawitz, P.; Graul-Neumann, L; Doelken, S.; Ehmke, N.; Spielmann, M.; Oien, N.C.; Schweiger, M R; Krueger, U; Frommer, G.; Fischer, B.

    2014-01-01

    Less than half of patients with suspected genetic disease receive a molecular diagnosis. We have therefore integrated next-generation sequencing (NGS), bioinformatics, and clinical data into an effective diagnostic workflow. We used variants in the 2741 established Mendelian disease genes [the disease-associated genome (DAG)] to develop a targeted enrichment DAG panel (7.1 Mb), which achieves a coverage of 20-fold or better for 98% of bases. Furthermore, we established a computational method ...

  13. Immunoregulation of encephalitogenic MBP-NAc1-11-reactive T cells by CD4+ TCR-specific T cells involves IL-4, IL-10 and IFN-gamma.

    Science.gov (United States)

    Adlard, K; Tsaknardis, L; Beam, A; Bebo, B F; Vandenbark, A A; Offner, H

    1999-01-01

    The generation of TCR transgenic (Tg) mice expressing a BV8S2 (Vbeta8 subfamily 2) chain specific for the encephalitogenic NAc1-11 region of MBP provides a unique system for evaluating the mechanisms involved in anti-TCR immunoregulation of EAE. In a previous study, we showed that vaccination with BV8S2 protein induced specific T cells that inhibited proliferation responses and encephalitogenic activity of MBP-reactive T cells in vitro, and resulted in a skewed production of Th2 cytokines by the MBP-reactive T cells. These data suggested that regulation of the encephalitogenic T cells was mediated by inhibitory cytokines rather than through a deletional mechanism. In the current study, we have employed the BV8S2 Tg mouse model to address the issue of which cytokines produced by anti-TCR-reactive T cells can regulate the function of encephalitogenic Th1 cells. Utilizing neutralizing anti-cytokine antibodies to reverse inhibitory effects of supernatants from BV8S2-specific T cells, we found that IL-4, IL-10, and to a lesser extent, IFN-gamma and TGF-beta, were the major regulatory cytokines responsible for inhibiting encephalitogenic activity, proliferation, and IFN-gamma secretion of MBP-NAc1-11-reactive Th1 cells. These results indicate that cytokine regulation is the major mechanism through which TCR specific CD4+ T cells regulate encephalitogenic and potentially other bystander Th1 cells.

  14. 白细胞介素4、白细胞介素8、白细胞介素10在哮喘和慢性阻塞性肺疾病发病中的作用%Role of IL-4, IL-8 and IL-10 in Asthma and Chronic Obstructive Pulmonary Disease

    Institute of Scientific and Technical Information of China (English)

    崔丽英; 任卉; 郝璐; 高春桃

    2012-01-01

    Objective:Thc research aims at studying the role of peripheral blood intcricukin 4 (IL-4) , intcricukin 8 (IL-8) and intcricukin 10 (IL-10) in asthma and chronic obstructive pulmonary disease (COPD). Methods: Use double-antibody sandwich enzyme-linked immunosorbent assam (ELISA) to detect the content of scrum IL-4, IL-8 and IL-10 in 50 cases of acute exacerbation of COPD (AECOPD) , 50 cases of paracmastic COPD, 50 cases of acute asthma, 50 cases of paracmastic asthma and 50 cases of healthy volunteers (healthy control group). Results: The levels of IL-4 and IL-8 in the scrum of the patients with acute asthma were significantly higher than that of the paracmastic asthma group(P<0. 01) , while the levels of scrum IL-4,IL-8 in these two groups were significantly higher than that in the healthy group (PIL-4 and IL-8 in the scrum of the patients with AECOPD was significantly higher than that in the paracmastic COPD group(P<0. 01) , while the levels of scrum IL-4 and IL-8 in the two groups were significantly higher than that in the healthy group (P< 0. 01). The IL-10 level in the scrum of the patients with AECOPD was significantly lower than that of the paracmastic COPD group(P<0. 01) and the levels of scrum IL-10 in both groups were singnificantly lower than in the healthy group (PIL-4 level in the a-cutc asthma group was significantly higher than in the acute asthma group (PIL-4, IL-8 and IL-10 arc engaged in asthma and COPD airway inflammatory

  15. [Diagnosis and treatment of eye diseases associated with HIV infection and AIDS].

    Science.gov (United States)

    Geng, Shuang; Ye, Jun-Jie; Liu, Li-Qiu; Xu, Hai-Yan; Wang, Wei-Wei; Wang, Shu-Ran

    2009-12-01

    To investigate the manifestations and treatment principles of ocular diseases associated with human immunodeficiency virus infection (HIV) and acquired immunodeficiency syndrome (AIDS). It was a retrospective case series. One hundred and ten patients were recruited. Two hundred and twenty eyes underwent ophthalmologic examination that included vision acuity, anterior segment and fundus examinations with papillary dilation and fundus fluorescein angiography. CD(4)(+)T-lymphocyte was counted in peripheral blood of 110 patients. Intravitreal injection of ganciclovir 400 microg was performed in 4 eyes (2 patients) with cytomegalovirus (CMV) retinitis associated with AIDS. All statistical analyses were performed using SPSS 13.0 software. The association between the age, duration of HIV infection and HIV/AIDS related ocular manifestations was analyzed by Pearson Correlation Analysis. The association between the gender and HIV/AIDS related ocular manifestations was analyzed by Pearson Chi-Square test. For comparison of the CD(4)(+)T cells counts of the patients with normal fundus, HIV retinopathy, CMV retinitis, Kruskal-Wallis Test for Several Independent Samples was used. Baseline visual acuity: no light perception (NLP) 5 eyes; light perception (LP) to 0.04, 10 eyes; 0.05 to 0.2, 14 eyes; 0.3 to 0.7, 62 eyes and >/= 0.8, 129 eyes. Small grayish keratin precipitates or pigment keratin precipitates were present in 25 eyes, 22 eyes had positive aqueous flare, 4 eyes had posterior synechia of the iris, 28 eyes had cataract. HIV retinopathy was present in 34 eyes. Cotton-wool spots, retinal hemorrhages, and retinal microaneurysms were found in eyes with HIV retinopathy. CMV retinitis was present in 32 eyes. The fundus manifestations of CMV retinitis included retinal vasculitis; dense, full-thickness, yellow-white lesions along vascular distribution with irregular granules at the border, and hemorrhage on the retinal surface in 26 eyes. Late stage retinopathy was demonstrated

  16. Disease-associated changes in the expression of ion channels, ion receptors, ion exchangers and Ca(2+)-handling proteins in heart hypertrophy.

    Science.gov (United States)

    Zwadlo, Carolin; Borlak, Jürgen

    2005-09-15

    The molecular pathology of cardiac hypertrophy is multifactorial with transcript regulation of ion channels, ion exchangers and Ca(2+)-handling proteins being speculative. We therefore investigated disease-associated changes in gene expression of various ion channels and their receptors as well as ion exchangers, cytoskeletal proteins and Ca(2+)-handling proteins in normotensive and spontaneously hypertensive (SHR) rats. We also compared experimental findings with results from hypertrophic human hearts, previously published (Borlak, J., and Thum, T., 2003. Hallmarks of ion channel gene expression in end-stage heart failure. FASEB J. 17, 1592-1608). We observed significant (P ion exchangers (Atp1A1, NCX-1, SERCA2a), ion channels (L-type Ca(2+)-channel, K(ir)3.4, Na(v)1.5) and RyR-2 in hypertrophic hearts, while gene expression was repressed in diseased human hearts. Further, the genes coding for calreticulin and calmodulin, PMCA 1 and 4 as well as alpha-skeletal actin were significantly (P diseased human and rat hearts. Our study enabled an identification of disease-associated candidate genes. Their regulation is likely to be the result of an imbalance between pressure load/stretch force and vascular tonus and the observed changes may provide a rational for the rhythm disturbances observed in patients with cardiac hypertrophy.

  17. A case of interstitial lung disease associated with clinically amyopathic dermatomyositis: radiologic-pathologic correlation.

    Science.gov (United States)

    Okubo, Gosuke; Noma, Satoshi; Nishimoto, Yuko; Sada, Ryuichi; Kobashi, Yoichiro

    2013-01-01

    This case report describes a 64-year-old woman with interstitial lung disease associated with clinically amyopathic dermatomyositis. Chest computed tomography revealed consolidations along bronchovascular bundles in the periphery of the lower lungs. Interstitial lung disease developed acutely, and the patient died 3 months after the clinical diagnosis. An autopsy was performed, and a large section of the lung specimen was prepared. Various interstitial lesions including organizing pneumonia, cellular and fibrotic nonspecific interstitial pneumonia, and diffuse alveolar damage were seen in the large section. Correlating the large section and computed tomography images was useful for determining the distribution of diffuse alveolar damage.

  18. 溃疡性结肠炎患者结肠粘膜培养液中三种细胞因子的表达及临床研究%Expression and Role of IL-4,IFN-γ,TNF-ɑ in Culture Supernateof Colonic Mucosa with Ulcerative Colitis Patients

    Institute of Scientific and Technical Information of China (English)

    王志红; 赵晓军; 韩英

    2008-01-01

    研究溃疡性结肠炎患者(Ulcerative Colitis,UC)与对照者结肠粘膜培养上清液中白介素-4(InterLeukin 4,IL-4)、干扰素-γ(InterFeron Gamma,IFN-γ)和肿瘤坏死因子-ɑ(Tumour Nerosis Factor alpha,TNF-ɑ)的表达及临床意义.采用ELISA法定量检测UC患者及对照者结肠粘膜培养上清液中IL-4 、IFN-γ、TNF-ɑ的表达情况.结果活动期UC患者结肠粘膜培养上清液中IL-4表达低于对照组(分别为0.159 1±0.101 4、0.342 3 ±0.049 7,P< 0.05),而IFN-γ和TNF-ɑ表达均高于对照组(分别为1.448 1± 1.166 1、1.834 9±1.641 7,P<0.01).说明 IL-4表达下调、而IFN-γ、TNF-ɑ表达上调的改变可能是UC发生发展过程中的重要因素之一.

  19. Reverse Nearest Neighbor Search on a Protein-Protein Interaction Network to Infer Protein-Disease Associations.

    Science.gov (United States)

    Suratanee, Apichat; Plaimas, Kitiporn

    2017-01-01

    The associations between proteins and diseases are crucial information for investigating pathological mechanisms. However, the number of known and reliable protein-disease associations is quite small. In this study, an analysis framework to infer associations between proteins and diseases was developed based on a large data set of a human protein-protein interaction network integrating an effective network search, namely, the reverse k-nearest neighbor (RkNN) search. The RkNN search was used to identify an impact of a protein on other proteins. Then, associations between proteins and diseases were inferred statistically. The method using the RkNN search yielded a much higher precision than a random selection, standard nearest neighbor search, or when applying the method to a random protein-protein interaction network. All protein-disease pair candidates were verified by a literature search. Supporting evidence for 596 pairs was identified. In addition, cluster analysis of these candidates revealed 10 promising groups of diseases to be further investigated experimentally. This method can be used to identify novel associations to better understand complex relationships between proteins and diseases.

  20. Identification of a common lupus disease-associated microRNA expression pattern in three different murine models of lupus.

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    Rujuan Dai

    Full Text Available BACKGROUND: Recent reports have shown that microRNAs (miRNAs regulate vital immunological processes and have emerged as key regulators of immune system development and function. Therefore, it is important to determine miRNA dysregulation and its pathogenic contribution in autoimmune diseases, an aspect not adequately addressed thus far. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we profiled miRNA expressions in splenic lymphocytes from three murine lupus models (MRL-lpr, B6-lpr and NZB/W(F₁ with different genetic background by miRNA microarray assays and Real-time RT-PCR. Despite the genetic differences among these three lupus stains, a common set of dysregulated miRNAs (miR-182-96-183 cluster, miR-31, and miR-155 was identified in splenocytes when compared with age-matched control mice. The association of these miRNAs with the disease was highlighted by our observation that this miRNA expression pattern was evident in NZB/W mice only at an age when lupus disease is manifested. Further, we have shown that the miRNA dysregulation in MRL-lpr mice was not simply due to the activation of splenocytes. By Real-time RT-PCR, we confirmed that these miRNAs were upregulated in both purified splenic B and T cells from MRL-lpr mice. miR-127 and miR-379, which were greatly upregulated in splenocytes from lpr mice, were moderately increased in diseased NZB/W mice. In addition, Real-time RT-PCR revealed that miR-146a, miR-101a, and miR-17-92 were also markedly upregulated in splenic T, but not B cells from MRL-lpr mice. CONCLUSIONS/SIGNIFICANCE: The identification of common lupus disease-associated miRNAs now forms the basis for the further investigation of the pathogenic contribution of these miRNAs in autoimmune lupus, which will advance our knowledge of the role of miRNAs in autoimmunity. Given that miRNAs are conserved, with regard to both evolution and function, our observation of a common lupus disease-associated miRNA expression pattern in murine

  1. Effect of IL-10 gene transfer on expression of IL-12,IL-15,IL-18 and IL-4 in mice heart transplantation rejection%白细胞介素10基因转染对小鼠心脏移植排斥反应中细胞因子表达的影响

    Institute of Scientific and Technical Information of China (English)

    高思海; 潘铁成; 杨辰垣

    2004-01-01

    目的:探讨白细胞介素10(IL-10)基因转染对小鼠心脏移植排斥反应中IL-12、IL-15、IL-18和IL-4表达的影响.方法:采用小鼠颈部心脏移植模型,随机分为3组:对照组、移植组和IL-10组.于术后第5天取移植心脏,用逆转录聚合酶链式反应(RT-PCR)法观察IL-12、IL-15、IL-18、IL-4及IL-10的表达情况.结果:移植组IL-12、IL-15、IL-18表达与对照组比较明显升高,IL-10、 IL-4表达显著降低(均P<0.01).IL-10组IL-12、IL-15、IL-18表达与移植组比较明显降低,而IL-4及IL-10表达显著升高(均P<0.01).结论:IL-10基因转染抑制心脏移植排斥反应主要与其抑制IL-12、IL-15、IL-18等Th1型细胞因子的表达,促进Th2型细胞因子IL-4的表达,使免疫反应由Th1型向Th2型偏移有关.

  2. Prediction and validation of gene-disease associations using methods inspired by social network analyses.

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    U Martin Singh-Blom

    Full Text Available Correctly identifying associations of genes with diseases has long been a goal in biology. With the emergence of large-scale gene-phenotype association datasets in biology, we can leverage statistical and machine learning methods to help us achieve this goal. In this paper, we present two methods for predicting gene-disease associations based on functional gene associations and gene-phenotype associations in model organisms. The first method, the Katz measure, is motivated from its success in social network link prediction, and is very closely related to some of the recent methods proposed for gene-disease association inference. The second method, called Catapult (Combining dATa Across species using Positive-Unlabeled Learning Techniques, is a supervised machine learning method that uses a biased support vector machine where the features are derived from walks in a heterogeneous gene-trait network. We study the performance of the proposed methods and related state-of-the-art methods using two different evaluation strategies, on two distinct data sets, namely OMIM phenotypes and drug-target interactions. Finally, by measuring the performance of the methods using two different evaluation strategies, we show that even though both methods perform very well, the Katz measure is better at identifying associations between traits and poorly studied genes, whereas Catapult is better suited to correctly identifying gene-trait associations overall [corrected].

  3. Interleukin-4 Induces CpG Site-Specific Demethylation of the Pendrin Promoter in Primary Human Bronchial Epithelial Cells

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    Giada Scantamburlo

    2017-03-01

    Full Text Available Pendrin is upregulated in bronchial epithelial cells following IL-4 stimulation via binding of STAT6 to an N4 GAS motif. Basal CpG methylation of the pendrin promoter is cell-specific. We studied if a correlation exists between IL-4 sensitivity and the CpG methylation status of the pendrin promoter in human bronchial epithelial cell models. Methods: Real-time PCR and pyrosequencing were used to respectively quantify pendrin mRNA levels and methylation of pendrin promoter, with and without IL-4 stimulation, in healthy and diseased primary HBE cells, as well as NCI-H292 cells. Results: Increases in pendrin mRNA after IL-4 stimulation was more robust in NCI-H292 cells than in primary cells. The amount of gDNA methylated varied greatly between the cell types. In particular, CpG site 90 located near the N4 GAS motif was highly methylated in the primary cells. An additional CpG site (90bis, created by a SNP, was found only in the primary cells. IL-4 stimulation resulted in dramatic demethylation of CpG sites 90 and 90bis in the primary cells. Conclusions: IL-4 induces demethylation of specific CpG sites within the pendrin promoter. These epigenetic alterations are cell type specific, and may in part dictate pendrin mRNA transcription.

  4. Circulating CD4+ T cells that produce IL4 or IL17 when stimulated by melan-A but not by NY-ESO-1 have negative impacts on survival of patients with stage IV melanoma.

    Science.gov (United States)

    Zelba, Henning; Weide, Benjamin; Martens, Alexander; Derhovanessian, Evelyna; Bailur, Jithendra Kini; Kyzirakos, Christina; Pflugfelder, Annette; Eigentler, Thomas K; Di Giacomo, Anna Maria; Maio, Michele; Aarntzen, Erik H J G; de Vries, Jolanda; Sucker, Antje; Schadendorf, Dirk; Büttner, Petra; Garbe, Claus; Pawelec, Graham

    2014-08-15

    We initially observed that the presence of circulating NY-ESO-1- and/or Melan-A-specific T cells in patients with stage IV melanoma was significantly associated with prolonged survival. Here, we report the ways in which the phenotypes and functions of these T cells differentially affect survival in patients preselected for NY-ESO-1 and/or Melan-A reactivity. We assayed functional antigen-reactive T cells recognizing NY-ESO-1 and/or Melan-A after in vitro stimulation using overlapping peptide pools. After restimulation, we assayed six cytokines simultaneously by intracellular cytokine staining. This allowed us to analyze the functional antigen response of both CD4(+) and CD8(+) T cells at the single-cell level. We observed that NY-ESO-1 stimulated mainly CD4(+) T cells, whereas Melan-A more often stimulated CD8(+) T cells. NY-ESO-1 reactivity was not associated with an additional impact on survival, whether CD4(+) T cells, CD8(+) T cells, or both types of T cells were responding. In contrast, recognition of Melan-A by CD4(+) T cells was associated with reduced survival in our cohort of patients preselected for NY-ESO-1 and/or Melan-A reactivity (that is, in patients with exceptionally long survival). We further observed a negative effect on survival in patients with CD4(+) T cells producing IL4 and IL17 upon Melan-A stimulation. Their prognosis was comparable to patients without any Melan-A reactivity. The nature and prognostic impact of specific T-cell responses is different according to targeted antigen. Independent from phenotype and functional aspects, NY-ESO-1 reactivity is associated with good prognosis. In terms of Melan-A, antigen-specific CD8(+) but not CD4(+) responses are associated with prolonged survival. Clin Cancer Res; 20(16); 4390-9. ©2014 AACR. ©2014 American Association for Cancer Research.

  5. Incomplete Kawasaki disease associated with complicated Streptococcus pyogenes pneumonia: A case report.

    Science.gov (United States)

    Leahy, Timothy Ronan; Cohen, Eyal; Allen, Upton D

    2012-01-01

    A three-year-old boy presented with community-acquired pneumonia complicated by empyema. Streptococcus pyogenes (group A streptococcus) was identified on culture of the pleural fluid. The patient improved with antibiotic therapy and drainage of the empyema. During his convalescence, the patient developed persistent fever, lethargy and anorexia. His inflammatory markers were elevated, and repeat cultures were negative. Although the patient had none of the classical mucocutaneous features of Kawasaki disease, an echocardiogram was performed, which revealed coronary artery dilation. The patient was diagnosed with incomplete Kawasaki disease and treated with intravenous immunoglobulin and high-dose acetylsalicylic acid. The fever subsided within 48 h. To the authors' knowledge, the present report is the first report of Kawasaki disease associated with complicated S pyogenes pneumonia. It emphasizes the importance of considering incomplete Kawasaki disease among children with persistent fever, the role of echocardiography in diagnosis, and the potential link between Kawasaki disease and superantigen-producing organisms such as S pyogenes.

  6. Ulcerative enteritis-like disease associated with Clostridium sordellii in quail.

    Science.gov (United States)

    Crespo, Rocio; Franca, Monique; Shivaprasad, H L

    2013-09-01

    A natural outbreak of ulcerative enteritis-like disease associated with Clostridium sordellii was diagnosed in two commercial quail flocks. Clinical signs in the quail included anorexia, weakness, and increased mortality in the flocks. Lesions in the intestine were characterized by ulcers covered with fibrinonecrotic exudate in the small intestine and occasional hemorrhages. There were also multifocal pale areas of necrosis in the liver. Clostridium sordellii was isolated from the intestine and liver. A retrospective study of avian cases submitted to the California Animal Health and Food Safety Laboratories revealed that C. sordellii had been isolated in 45 avian submissions, most commonly in chickens and turkeys. In most of these cases the birds were diagnosed with necrotic enteritis, with or without hepatitis. Clostridium sordellii has occasionally been associated with gangrenous dermatitis in poultry, but this is the first report of enteritis in an avian species.

  7. Complete genome sequence of Colocasia bobone disease-associated virus, a putative cytorhabdovirus infecting taro.

    Science.gov (United States)

    Higgins, Colleen M; Bejerman, Nicolas; Li, Ming; James, Anthony P; Dietzgen, Ralf G; Pearson, Michael N; Revill, Peter A; Harding, Robert M

    2016-03-01

    We report the first genome sequence of a Colocasia bobone disease-associated virus (CBDaV) derived from bobone-affected taro [Colocasia esculenta L. Schott] from Solomon Islands. The negative-strand RNA genome is 12,193 nt long, with six major open reading frames (ORFs) with the arrangement 3'-N-P-P3-M-G-L-5'. Typical of all rhabdoviruses, the 3' leader and 5' trailer sequences show complementarity to each other. Phylogenetic analysis indicated that CBDaV is a member of the genus Cytorhabdovirus, supporting previous reports of virus particles within the cytoplasm of bobone-infected taro cells. The availability of the CBDaV genome sequence now makes it possible to assess the role of this virus in bobone, and possibly alomae disease of taro and confirm that this sequence is that of Colocasia bobone disease virus (CBDV).

  8. [Revised consensus classification. Histopathological classification of diseases associated with joint endoprostheses].

    Science.gov (United States)

    Krenn, V; Morawietz, L; Kienapfel, H; Ascherl, R; Matziolis, G; Hassenpflug, J; Thomsen, M; Thomas, P; Huber, M; Schuh, C; Kendoff, D; Baumhoer, D; Krukemeyer, M G; Perino, G; Zustin, J; Berger, I; Rüther, W; Poremba, C; Gehrke, T

    2013-05-01

    The revised classification of the periprosthetic membrane (synovial-like interface membrane SLIM) encompasses all pathological alterations which can occur as a result of endoprosthetic replacement of major joints and lead to a reduction in durability of prostheses. This also includes the established consensus classification of SLIM by which aseptic and septic prosthetic loosening can be subdivided into four histological types and histopathological criteria for additional pathologies: endoprosthesis-associated arthrofibrosis, immunological/allergic alterations and osseous pathologies. This revision represents the foundation for the histopathological diagnostics of the total spectrum of diseases associated with joint prostheses, is a suitable basis for a standardized diagnostic procedure and etiological clarification of endoprosthesis failure and also as a data standard for endprosthesis registers, in particular for registers based on routine data (e.g. German endoprosthesis register).

  9. Genetic Similarity between Cotton Leafroll Dwarf Virus and Chickpea Stunt Disease Associated Virus in India

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    Arup Kumar Mukherjee

    2016-12-01

    Full Text Available The cotton leafroll dwarf virus (CLRDV is one of the most devastating pathogens of cotton. This malady, known as cotton blue disease, is widespread in South America where it causes huge crop losses. Recently the disease has been reported from India. We noticed occurrence of cotton blue disease and chickpea stunt disease in adjoining cotton and chickpea fields and got interested in knowing if these two viral diseases have some association. By genetic studies, we have shown here that CLRDV is very close to chickpea stunt disease associated virus (CpSDaV. We were successful in transmitting the CLRDV from cotton to chickpea. Our studies indicate that CpSDaV and CLRDV in India are possibly two different strains of the same virus. These findings would be helpful in managing these serious diseases by altering the cropping patterns.

  10. Sherlock: detecting gene-disease associations by matching patterns of expression QTL and GWAS.

    Science.gov (United States)

    He, Xin; Fuller, Chris K; Song, Yi; Meng, Qingying; Zhang, Bin; Yang, Xia; Li, Hao

    2013-05-01

    Genetic mapping of complex diseases to date depends on variations inside or close to the genes that perturb their activities. A strong body of evidence suggests that changes in gene expression play a key role in complex diseases and that numerous loci perturb gene expression in trans. The information in trans variants, however, has largely been ignored in the current analysis paradigm. Here we present a statistical framework for genetic mapping by utilizing collective information in both cis and trans variants. We reason that for a disease-associated gene, any genetic variation that perturbs its expression is also likely to influence the disease risk. Thus, the expression quantitative trait loci (eQTL) of the gene, which constitute a unique "genetic signature," should overlap significantly with the set of loci associated with the disease. We translate this idea into a computational algorithm (named Sherlock) to search for gene-disease associations from GWASs, taking advantage of independent eQTL data. Application of this strategy to Crohn disease and type 2 diabetes predicts a number of genes with possible disease roles, including several predictions supported by solid experimental evidence. Importantly, predicted genes are often implicated by multiple trans eQTL with moderate associations. These genes are far from any GWAS association signals and thus cannot be identified from the GWAS alone. Our approach allows analysis of association data from a new perspective and is applicable to any complex phenotype. It is readily generalizable to molecular traits other than gene expression, such as metabolites, noncoding RNAs, and epigenetic modifications.

  11. Crohn's disease-associated adherent-invasive Escherichia coli adhesion is enhanced by exposure to the ubiquitous dietary polysaccharide maltodextrin.

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    Kourtney P Nickerson

    Full Text Available Crohn's disease (CD is associated with intestinal dysbiosis evidenced by an altered microbiome forming thick biofilms on the epithelium. Additionally, adherent-invasive E. coli (AIEC strains are frequently isolated from ileal lesions of CD patients indicating a potential role for these strains in disease pathogenesis. The composition and characteristics of the host microbiome are influenced by environmental factors, particularly diet. Polysaccharides added to food as emulsifiers, stabilizers or bulking agents have been linked to bacteria-associated intestinal disorders. The escalating consumption of polysaccharides in Western diets parallels an increased incidence of CD during the latter 20(th century. In this study, the effect of a polysaccharide panel on adhesiveness of the CD-associated AIEC strain LF82 was analyzed to determine if these food additives promote disease-associated bacterial phenotypes. Maltodextrin (MDX, a polysaccharide derived from starch hydrolysis, markedly enhanced LF82 specific biofilm formation. Biofilm formation of multiple other E. coli strains was also promoted by MDX. MDX-induced E. coli biofilm formation was independent of polysaccharide chain length indicating a requirement for MDX metabolism. MDX exposure induced type I pili expression, which was required for MDX-enhanced biofilm formation. MDX also increased bacterial adhesion to human intestinal epithelial cell monolayers in a mechanism dependent on type 1 pili and independent of the cellular receptor CEACAM6, suggesting a novel mechanism of epithelial cell adhesion. Analysis of mucosa-associated bacteria from individuals with and without CD showed increased prevalence of malX, a gene essential for MDX metabolism, uniquely in the ileum of CD patients. These findings demonstrate that the ubiquitous dietary component MDX enhances E. coli adhesion and suggests a mechanism by which Western diets rich in specific polysaccharides may promote dysbiosis of gut microbes

  12. Expressions of IFN-γ、JL-4 and IL-10 and their Relations with Islet Beta Cell Function in Adults with Latent Autoimmune Diabetes%LADA的IFN-γ、IL-4、IL-10水平及其与胰岛β细胞功能的关系

    Institute of Scientific and Technical Information of China (English)

    张士荣; 张晓梅; 毕娅欣; 周静; 张林杰

    2010-01-01

    目的 探讨成人隐匿性自身免疫糖尿病(LADA)患者IFN-γ、IL-4、IL-10水平变化及其与胰岛β细胞功能的关系.方法 ELISA法检测20例1型糖尿病患者、20例LADA患者、20例2型糖尿病患者、20例正常对照外周血血清中IFN-γ、IL-4、IL-10水平,放免法测定C-肽和胰岛素的空腹及餐后2 h水平,评价胰岛β细胞功能.结果 与对照组相比,3组IFN-γ、IL4、IL-10水平均有显著升高.IFN-γ测定结果显示LADA组低于T1DM组,高于T2DM组;IL-4和IL-10测定结果显示LADA组低于T2DM组,高于T1DM组.T1DM组和LADA组空腹及餐后2 h C-肽和胰岛素显著降低,T2DM组和对照组空腹C-肽和胰岛素无显著差异,餐后2 h C-肽和胰岛素均显著增高.结论 LADA患者细胞因子水平紊乱,导致细胞免疫功能失衡,可能是其胰岛β细胞功能损害的因素之一.

  13. Effects of baicalin on serum levels of IL-6 and IL-4 in mouse periodontitis%黄芩甙对牙周炎小鼠血清白细胞介素-6和白细胞介素-4水平的影响

    Institute of Scientific and Technical Information of China (English)

    饶利佳; 卢嘉健; 吕芳丽; 李东健; 黄世光

    2011-01-01

    AIM : To investigate the effect of baicalin on experimental periodontitis in mouse model by comparing the histological changes in periodontal tissues and serum levels of inter leukin( IL ) - 6/IL -4 in mice, and to analyze the role of baicalin in immune regulation and anti - inflammatory mechanisms.METHODS : Twenty - seven male Kunming mice ( SPF grade, 12 - week - old ) were randomly divided into 3 groups.The naive mice were used in normal control group.In experimental periodontitis group, the periodontitis model was produced by ligature of braided silk around the first maxillary molar and inoculation with putative periodontopathic bacteria.Five weeks after the ligature, the mice were fed with 10% glucose, and gavaged with distilled water.In baicalin treatment + periodontitis group, the periodontitis model was induced as above, then gavaged with baicalin at the beginning of the fifth week after the ligature.The mice were sacrificed at week 4.6 and 8.The histological changes of the periodontal tissues were observed under microscope with hematoxylin and eosin ( HE ) staining.The serum level of IL -6 and IL -4 in the mice were determined by ELISA.RESULTS :The periodontal tissues showed moderate inflammatory damages in experimental periodontitis group.The periodontal destruction was significantly reduced in baicalin treatment + periodontitis group.The serum level of IL - 6 in experimental periodontitis group was significantly higher than that in control group and baicalin treatment + periodontitis group ( P < 0.01 ) ,and the serum level of IL - 6 in haicalin treatment + periodontitis group was significantly lower than that in periodontitis group at week 6 and 8 ( P < 0.01 ).The serum level of IL -4 in periodontitis group was significantly lower than that in control and baicalin treatment +periodontitis group ( P < 0.01 ).The serum level of IL - 4 in baicalin treatment + periodontitis group was significantly higher than that in periodontitis group at weeks 6

  14. Detection of Levels of IL-2/IL-10 and Promoting Th2 Molecular IL-4 in Peripheral Blood of Gestational Hypertension%妊娠高血压外周血中促Th2的细胞因子水平及IL-2/IL-10平衡的临床意义

    Institute of Scientific and Technical Information of China (English)

    肖文辉; 钟荣钟; 林洁; 彭耀金

    2011-01-01

    目的:检测妊娠高血压患者外周血中促Th2的分子IL-4、IL-2与IL-10的水平,探讨IL-2/IL-10在妊高症中的临床意义.方法:选择40例未妊娠妇女为对照组,30例正常妊娠妇女为妊娠组,28例妊娠高血压患者为妊娠高血压组,ELISA检测血清中IL-4、IL-2和IL-10的水平.结果:与对照组外周血中IL-4水平(0.53±0.04)pg/ml相比:正常妊娠组IL-4水平升高至(0.91±0.03)pg/ml(P<0.05),妊娠高血压组II-4水平(0.67±0.35)pg/ml升高但明显低于正常妊娠组(P<0.01).与对照组外周血中IL-2水平(0.41±0.05)pg/ml相比:正常妊娠组IL-2水平升高至(0.82±0.11)pg/ml(P<0.01);妊娠高血压组IL-2水平高达1.57±0.22(pg/ml)明显高于其它两组(P<0.01).妊娠高血压组外周血中IL-10水平明显低于正常妊娠组IL-10水平(P<0.01);妊娠高血压组外周血中IL-2/IL-10比值明显高于于对照组及正常妊娠组的比值.结论:妊娠高血压患者外周血中细胞因子IL-2和IL-10分泌异常且诱导Th2细胞产生的IL-4降低,打破Th1/Th2平衡,致使Th1型免疫反应增强,使早孕期滋养细胞受到免疫损伤以致侵入能力下降,导致妊娠期高血压疾病的发生.%Objective: To detect the levels of IL-4 and IL-2 and IL-10 in the patients with pregnancy-induced hypertension, and discuss the detection of IL-2/IL-10. Methods: Taking 40 cases of non-pregnant women as control group, 30 normal pregnant women as pregnancy group, 28 cases of pregnancy induced hypertension as pregnancy-induced hypertension group patients, we used ELISA to detect the levels of IL-4, IL-2 and IL-10 in their serum. Results: The levels of IL-4 in peripheral blood of pregnancy group was (0.91± 0.03) pg / ml, significantly higher than the level of IL-4 (0.53 ± 0.04) pg / ml in control group (P<0.05). The levels of IL-4 in peripheral blood of pregnancy-induced hypertension group was (0.67± 0.35) pg / ml, significantly lower than the IL-4 level in normal pregnancy group (P

  15. Treatment strategies in the left main coronary artery disease associated with acute coronary syndromes

    Directory of Open Access Journals (Sweden)

    Ahmet Karabulut

    2015-10-01

    Full Text Available Significant left main coronary artery (LMCA stenosis is not rare and reported 3 to 10% of patients undergoing coronary angiography. Unprotected LMCA intervention is a still clinical challenge and surgery is still going to be a traditional management method in many cardiac centers. With a presentation of drug eluting stent (DES, extensive use of IVUS and skilled operators, number of such interventions increased rapidly which lead to change in recommendation in the guidelines regarding LMCA procedures in the stable angina (Class 2a recommendation for ostial and shaft lesion and class 2b recommendation for distal bifurcation lesion. However, there was not clear consensus about the management of unprotected LMCA lesion associated with acute myocardial infarction (MI with a LMCA culprit lesion itself or distinct culprit lesion of other major coronary arteries. Surgery could be preferred as an obligatory management strategy even in the high risk patients. With this review, we aimed to demonstrate treatment strategies of LMCA disease associated with acute coronary syndrome, particularly acute myocardial infarction (MI. In addition, we presented a short case series with LMCA lesion and ST elevated acute MI in which culprit lesion placed either in the left anterior descending artery or circumflex artery. We reviewed the current medical literature and propose simple algorithm for management.