WorldWideScience

Sample records for chemotactic protein-1 mcp-1

  1. Monocyte chemotactic protein-1 gene polymorphism and spontaneous bacterial peritonitis

    Institute of Scientific and Technical Information of China (English)

    Levent; Filik

    2010-01-01

    I read with great interest the article by Gbele et al published in issue 44 of World J Gastroenterol 2009.The results of their study indicate that-2518 Monocyte chemotactic protein-1(MCP-1)genotype AA is a risk factor for spontaneous bacterial peritonitis in patients with alcoholic cirrhosis.However,there are some items that need to be discussed.

  2. Monocyte chemotactic protein-1 expression in coronary atherosclerosis plaque of sudden coronary death patients

    Institute of Scientific and Technical Information of China (English)

    冯相平

    2006-01-01

    Objective To investigate the expression of monocyte chemotactic protein 1 (MCP-1) in coronary atherosclerosis plaque of sudden coronary death (SCD) patients and the relationship between MCP-1 expression and SCD. Methods Autopsy heart samples (n=90) collected during 2001 - 2003 were divided to SCD group (n=

  3. Monocyte chemotactic protein-1 expression as a prognosic biomarker in patients with solid tumor: a meta analysis

    OpenAIRE

    Wang, Hong; Zhang, Qiongwen; Kong, Hongyu; Zeng, Yunhui; Hao, Meiqin; Yu, Ting; Peng, Jing; Xu, Zhao; Chen, Jingquan; Shi, Huashan

    2014-01-01

    Purpose: A great deal of studies have been performed on the prognostic value of monocyte chemotactic protein-1 (MCP-1) in solid tumors in recent years. However, no consistent outcomes are reported. Therefore, the prognostic value of MCP-1 still remains controversial in patients with solid tumors. Here we aimed to evaluate the prognostic value of MCP-1 expression for patients with solid tumors. Methods: Comprehensive literature was selected from PUBMED and EMBASE and clinical studies which rep...

  4. Monocyte chemoattractant protein-1 (MCP-1 regulates macrophage cytotoxicity in abdominal aortic aneurysm.

    Directory of Open Access Journals (Sweden)

    Qiwei Wang

    Full Text Available AIMS: In abdominal aortic aneurysm (AAA, macrophages are detected in the proximity of aortic smooth muscle cells (SMCs. We have previously demonstrated in a murine model of AAA that apoptotic SMCs attract monocytes and other leukocytes by producing MCP-1. Here we tested whether infiltrating macrophages also directly contribute to SMC apoptosis. METHODS AND RESULTS: Using a SMC/RAW264.7 macrophage co-culture system, we demonstrated that MCP-1-primed RAWs caused a significantly higher level of apoptosis in SMCs as compared to control macrophages. Next, we detected an enhanced Fas ligand (FasL mRNA level and membrane FasL protein expression in MCP-1-primed RAWs. Neutralizing FasL blocked SMC apoptosis in the co-culture. In situ proximity ligation assay showed that SMCs exposed to primed macrophages contained higher levels of receptor interacting protein-1 (RIP1/Caspase 8 containing cell death complexes. Silencing RIP1 conferred apoptosis resistance to SMCs. In the mouse elastase injury model of aneurysm, aneurysm induction increased the level of RIP1/Caspase 8 containing complexes in medial SMCs. Moreover, TUNEL-positive SMCs in aneurysmal tissues were frequently surrounded by CD68(+/FasL(+ macrophages. Conversely, elastase-treated arteries from MCP-1 knockout mice display a reduction of both macrophage infiltration and FasL expression, which was accompanied by diminished apoptosis of SMCs. CONCLUSION: Our data suggest that MCP-1-primed macrophages are more cytotoxic. MCP-1 appears to modulate macrophage cytotoxicity by increasing the level of membrane bound FasL. Thus, we showed that MCP-1-primed macrophages kill SMCs through a FasL/Fas-Caspase8-RIP1 mediated mechanism.

  5. Effect of Monocyte Chemotactic Protein-1 on the Intraperitoneal Adhesion Formation

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    In order to study the role of monocyte chemotactic protein-1 (MCP-1) in the intra-peritoneal adhesion formation, 23 infertile patients undergoing laparoscopic operation were divided into two groups: experimental group including 12 patients with intra-peritoneal adhesion and control group including 11 patients without intra-peritoneal adhesion. Peritoneal fluid (PF) and peritoneum were collected from these patients during laparoscopic examination. The expression levels of MCP-l protein and MCP-1 mRNA were detected by using enzyme-linked immunosorbent assay (ELISA) and dot blot analysis method respectively. It was found that the levels of MCP-1 protein in PF of the patients with peritoneal adhesion were significantly higher than in the control group (0. 44±0.11 ng/ml vs 0. 19+0. 09 ng/ml respectively, P<0. 01 ). The level of MCP-1 mRNA in the peritoneum of the patients with peritoneal adhesion was significantly higher than in the control group (48.61±3.72 vs 19. 87±2.54 respectively, P<0. 01). It was suggested that MCP-1 might play a role in the adhesion formation, and chemotactic cytokines expressing in the peritoneal mesothelial cells might be take part in the process.

  6. Plasma Levels of Monocyte Chemotactic Protein-1 Are Associated with Clinical Features and Angiogenesis in Patients with Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Toni Valković

    2016-01-01

    Full Text Available The aim of this pilot study was to determine the plasma levels of monocyte chemotactic protein-1 (MCP-1 and possible associations with angiogenesis and the main clinical features of untreated patients with multiple myeloma (MM. ELISA was used to determine plasma MCP-1 levels in 45 newly diagnosed MM patients and 24 healthy controls. The blood vessels were highlighted by immunohistochemical staining, and computer-assisted image analysis was used for more objective and accurate determination of two parameters of angiogenesis: microvessel density (MVD and total vascular area (TVA. The plasma levels of MCP-1 were compared to these parameters and the presence of anemia, renal dysfunction, and bone lesions. A significant positive correlation was found between plasma MCP-1 concentrations and TVA (p=0.02. The MCP-1 levels were significantly higher in MM patients with evident bone lesions (p=0.01, renal dysfunction (p=0.02, or anemia (p=0.04. Therefore, our preliminary results found a positive association between plasma MCP-1 levels, angiogenesis (expressed as TVA, and clinical features in patients with MM. However, additional prospective studies with a respectable number of patients should be performed to authenticate these results and establish MCP-1 as a possible target of active treatment.

  7. Monocyte chemotactic protein-1 deficiency reduces spontaneous metastasis of Lewis lung carcinoma in mice fed a high-fat diet

    Science.gov (United States)

    Yan, Lin; Sundaram, Sneha

    2016-01-01

    Adipose-produced pro-inflammatory cytokines contribute to obesity and cancer. This 2×2 experiment was designed to investigate effects of monocyte chemotactic protein-1 (MCP-1) deficiency on pulmonary metastasis of Lewis lung carcinoma (LLC) in MCP-1 deficient and wild-type mice fed a modified AIN93G diet containing 16% and 45% of energy from corn oil, respectively. The high-fat diet significantly increased the number and size (cross-sectional area and volume) of lung metastases compared to the AIN93G control diet. Deficiency in MCP-1 reduced lung metastases by 37% in high-fat diet-fed mice; it reduced metastatic cross-sectional area by 46% and volume by 69% compared to wild-type mice. Adipose and plasma concentrations of MCP-1 were significantly higher in high-fat diet-fed wild-type mice than in their AIN93G-fed counterparts; they were not detectable in MCP-1 deficient mice regardless of diet. Plasma concentrations of plasminogen activator inhibitor-1, tumor necrosis factor-α, vascular endothelial growth factor and tissue inhibitor of metalloproteinase-1 were significantly higher in MCP-1 deficient mice compared to wild-type mice. We conclude that adipose-produced MCP-1 contributes to high-fat diet-enhanced metastasis. While MCP-1 deficiency reduces metastasis, the elevation of pro-inflammatory cytokines and angiogenic factors in the absence of MCP-1 may support the metastatic development and growth of LLC in MCP-1 deficient mice. PMID:27028862

  8. Elevated monocyte chemotactic proteins 1, 2, and 3 in pulmonary alveolar proteinosis are associated with chemokine receptor suppression.

    Science.gov (United States)

    Bonfield, Tracey L; John, Nejimol; Malur, Anagha; Barna, Barbara P; Culver, Daniel A; Kavuru, Mani S; Thomassen, Mary Jane

    2005-01-01

    Pulmonary alveolar proteinosis (PAP) is a rare autoimmune lung disease characterized by abnormal surfactant accumulation within alveolar macrophages, and circulating auto-antibodies against granulocyte-macrophage colony stimulating factor (GM-CSF) resulting in functional GM-CSF deficiency. Monocyte/macrophage chemotactic protein-1 (MCP-1) is elevated in PAP, suggesting association with the pathophysiology. Because PAP has been associated with inflammatory pulmonary changes, we hypothesized that other MCP family chemokines would be present and that Chemokine Chemotaxis Receptor 2 (CCR2) would be elevated on PAP mononuclear cells. Here we show for the first time that MCP-2 and MCP-3, like MCP-1, are highly elevated in PAP. We also confirm that PAP alveolar macrophages and not epithelial cells produce MCP-1, and that MCP-1 from PAP lung has functional chemoattractant activity. Surprisingly, CCR2 expression is diminished in PAP lymphocytes and alveolar macrophages compared to controls. Further, MCP-1 from PAP lung suppresses CCR2 expression in vitro, suggesting that in PAP, MCP-1 participates in an autocrine regulatory network in vivo. PMID:15596412

  9. Monocyte chemotactic protein 1 increases homing of mesenchymal stem cell to injured myocardium and neovascularization following myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective:To investigate the effect of MCP-1 on mesenchymal stem cells(MSCs) homing to injured myocardium in a rat myocardial infarction(MI) model. Methods:Rat myocardial infarction model was established by permanent left anterior descending branch ligation. Mesenchymal stem cells from donor rats were cultured in IMDM and labeled with BrdU. The Rats were divided into two groups. Monocyte chemotactic protein 1(MCP-1) expression were measured by in situ hybridization and immunohistochemistry in the sham operated or infarcted hearts at 1,2, 4,7,14 and 28 days post operation in MCP-1 detection group. The rats were injected with MCP-1, anti-MCP-1 antibody or saline 4 days after myocardial infarction in intervention group. Then, a total of 5 × 106 cells in 2.5 ml of PBS were injected through the tail vein. The number of the labeled MSCs in the infarcted hearts was counted 3 days post injection. Cardiac function and blood vessel density were assessed 28 days post injection. Results:Self-generating MCP-1 expression was increased at the first day, peaked at the 7th day and decreased thereafter post MI and remained unchanged in sham operated hearts. The MSCs enrichment in the host hearts were more abundant in the MI groups than that in the non-Mi group(P = 0.000), the MSCs enrichment in the host hearts were more abundant in the MCP-1 injected group than that in the anti-MCP-1 antibody and saline injected groups (P = 0.000). Cardiac function was improved more in MCP-1 injected group than anti-MCP-1 antibody and saline injected groups(P= 0.000). Neovascularization in MCP-1 injected group significantly increased compared with that of other groups(P = 0.000). Conclusion: Myocardial MCP-1 expression was increased only in the early phase post MI. MCP-1 may enhance MSCs homing to the injured heart and improve cardiac function by promoting neovascularization.

  10. Human monocyte-derived dendritic cells expressing both chemotactic cytokines IL-8, MCP-1, RANTES and their receptors,and their selective migration to these chemokines

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To characterize the mRNA expression of CXC chemokine IL-8, CC chemokine monocyte chemothractant protein-1 (MCP-1) and regulated on activation,normal T cell expressed and secreted (RANTES), and a newly defined DC chemokine DC- CK1 as well as the expression of IL-8 receptor, MCP-1 receptor and RANTES receptor in human monocyte derived dendritic cells (MoDCs).The migratory responsiveness of MoDC to IL-8, MCP-1 and RANTES was alsso studied. Methods In vitro generated MoDCs were obtained by differentiating monocytes in the presence of GM-CSF and IL-4 for 5 days. The time course of RNA expression was analyzed by RT-PCR and migratoly ability was assessed by a micromultiwell chemotaxis chamber assay. Results IL-8, MCP-1, RANTES and their corres ponding receptors were consistently expressed in MoDCs. DC-CK-1 expression was detectable efter 48 hours of differentiation. MoDC selectively migrated in response to MCP-1 and RANTES but not to IL-8 though transcripts of IL-8 receptor were present. Conclusion Because the capacity of dendritic cells to initiate immune responses depends on their specialized migratory and tissue homing properties, the expression of chemokines and their receptors along with the migratory responsiveness to chemokines of MoDC in our study suggests a potential role of chemokines in the interaction between dendritic cells and T cells and the induction of immune responses.

  11. Genome-wide association replicates the association of Duffy antigen receptor for chemokines (DARC) polymorphisms with serum monocyte chemoattractant protein-1 (MCP-1) levels in Hispanic children

    OpenAIRE

    Voruganti, V. Saroja.; Laston, Sandra; Haack, Karin; Mehta, Nitesh R.; Smith, C. Wayne; Cole, Shelley A.; Butte, Nancy F.; Comuzzie, Anthony G.

    2012-01-01

    Obesity is associated with a chronic low inflammatory state characterized by elevated levels of chemokines. Monocyte chemoattractant protein-1 (MCP-1) is a member of the cysteine-cysteine (CC) chemokine family and is increased in obesity. The purpose of this study was to identify loci regulating serum MCP-1 in obese Hispanic children from the Viva La Familia Study. A genome-wide association (GWA) analysis was performed in 815 children, ages 4-19 years, using genotypes assayed with the Illumin...

  12. Postoperative Changes in Aqueous Monocyte Chemotactic Protein-1 Levels and Bleb Morphology after Trabeculectomy vs. Ex-PRESS Shunt Surgery.

    Directory of Open Access Journals (Sweden)

    Kohei Shobayashi

    Full Text Available To evaluate the postoperative changes in blebs and levels of aqueous monocyte chemotactic protein-1 (MCP-1 after trabeculectomy vs. Ex-PRESS tube shunt surgery.Rabbits were subjected to trabeculectomy or Ex-PRESS tube shunt surgery and observed for up to 3 months. Intraocular pressure (IOP was measured using a rebound tonometer. The MCP-1 level was measured by enzyme-linked immunosorbent assay (ELISA. Bleb morphology was evaluated using photos and anterior-segment optical coherence tomography (OCT.There were no differences in bleb appearance or IOP at any time between the groups. Bleb wall density in the anterior-segment OCT image was significantly lower 1 week after surgery in the Ex-PRESS group than the trabeculectomy group. The MCP-1 level in control eyes was 304.1 ± 45.2 pg/mL. In the trabeculectomy group, the mean aqueous MCP-1 level was 1444.9, 1914.3, 1899.8, 516.4, 398.3, 427.3, 609.5, 1612.7, 386.2, and 167.9 pg/mL at 3, 6, and 12 h, and 1, 2, 5, 7, 14, 30, and 90 days after surgery, respectively. In the Ex-PRESS group, the corresponding values were 1744.0, 1372.0, 932.5, 711.7, 396.1, 487.3, 799.5, 1327.9, 293.6, and 184.0 pg/mL. There were no significant differences in the aqueous MCP-1 level between the groups at any time point.The postoperative changes were similar in the Ex-PRESS and trabeculectomy groups, except for bleb wall density in the anterior-segment OCT image. The postoperative aqueous MCP-1 level had bimodal peaks in both groups.

  13. Genome-wide association replicates the association of Duffy antigen receptor for chemokines (DARC) polymorphisms with serum monocyte chemoattractant protein-1 (MCP-1) levels in Hispanic children.

    Science.gov (United States)

    Voruganti, V Saroja; Laston, Sandra; Haack, Karin; Mehta, Nitesh R; Smith, C Wayne; Cole, Shelley A; Butte, Nancy F; Comuzzie, Anthony G

    2012-12-01

    Obesity is associated with a chronic low inflammatory state characterized by elevated levels of chemokines. Monocyte chemoattractant protein-1 (MCP-1) is a member of the cysteine-cysteine (CC) chemokine family and is increased in obesity. The purpose of this study was to identify loci regulating serum MCP-1 in obese Hispanic children from the Viva La Familia Study. A genome-wide association (GWA) analysis was performed in 815 children, ages 4-19 years, using genotypes assayed with the Illumina HumanOmni1-Quad v1.0 BeadChips. All analyses were performed in SOLAR using a linear regression-based test under an additive model of allelic effect, while accounting for the relatedness of family members via a kinship variance component. The strongest association for MCP-1 levels was found with a non-synonymous single nucleotide polymorphism (SNP), rs12075, resulting in an amino acid substitution (Asp42Gly) in the Duffy antigen receptor for chemokines (DARC) gene product (minor allele frequency=43.6%, p=1.3 × 10(-21)) on chromosome 1. Four other DARC SNPs were also significantly associated with MCP-1 levels (p<10(-16)-10(-6)). The Asp42Gly variant was associated with higher levels of MCP-1 and accounted for approximately 10% of its variability. In addition, MCP-1 levels were significantly associated with SNPs in chemokine receptor 3 (CCR3) and caspase recruitment domain family, member 9 (CARD9). In summary, the association of the DARC Asp42Gly variant with MCP-1 levels replicates previous GWA results substantiating a potential role for DARC in the regulation of pro-inflammatory cytokines. PMID:23017229

  14. Monocyte chemotactic protein-1 and soluble adhesion molecules as possible prognostic markers of the efficacy of antiviral treatment in chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Anatol Panasiuk; Danuta Prokopowicz; Bozena Panasiuk

    2004-01-01

    AIM: To explain the role of Monocyte chemotactic protein-1 (MCP-1) and soluble adhesion molecules in chronic hepatitis C during the treatment of interferon alpha (IFNα) 2 b and ribavirin (RBV).METHODS: Concentrations of MCP-1, soluble adhesion molecules intercellular adhesion molecule-1 (sICAM-1), sPselectin, interleukin (IL) 6, and IL10 in serum were estimated in the group of 40 patients with chronic hepatitis C treated with IFNalpha2 b and RBV in 0, 16, 32, 48 wk of the therapy.RESULTS: In chronic hepatitis C, before and during the treatment, the serum levels of MCP-1 and sP-selectin in responders were similar to those of healthy subjects. In nonresponders (NR), MCP-1 increased in the course of IFNα+RBV treatment, differences were statistically significant as compared to responders. MCP-1 correlated statistically with the activity of pedportal inflammation (r = 0.35, P<0.05) but not with staging of liver fibrosis. sICAM-1 positively correlated with inflammatory activity and fibrosis in NR. sP-selectin did not correlate with histological findings in the liver. The MCP-1 correlated with the soluble form of sP-selectin concentrations (r = 6, P<0.001) and with IL-10 level in NR (r = 0.4, P<0.05). There was no correlation observed between the concentration of MCP-1 and sICAM-1, IL-6 during the treatment.CONCLUSION: MCP-1 concentration may be a prognostic marker of the efficacy of IFN+RBV therapy in patients with chronic hepatitis C.

  15. Wound Healing in MIP-1α−/− and MCP-1−/− Mice

    OpenAIRE

    Low, Quentin E. H.; Drugea, Iulia A.; Duffner, Lisa A.; Quinn, Daniel G.; Cook, Donald N.; Rollins, Barrett J.; Kovacs, Elizabeth J.; DiPietro, Luisa A.

    2001-01-01

    A salient feature of normal wound healing is the development and resolution of an acute inflammatory response. Although much is known about the function of inflammatory cells within wounds, little is known about the chemotactic and activation signals that influence this response. As the CC chemokines macrophage inflammatory protein-1α (MIP-1α) and monocyte chemotactic protein-1 (MCP-1) are abundant in acute wounds, wound repair was examined in MIP-1α−/− and MCP-1−/− mice. Surprisingly, wound ...

  16. MCP-1 promotes mural cell recruitment during angiogenesis in the aortic ring model.

    Science.gov (United States)

    Aplin, Alfred C; Fogel, Eric; Nicosia, Roberto F

    2010-09-01

    Rings of rat or mouse aorta embedded in collagen gels produce angiogenic outgrowths in response to the injury of the dissection procedure. Aortic outgrowths are composed of branching endothelial tubes and surrounding mural cells. Mural cells emerge following endothelial sprouting and gradually increase during the maturation of the neovessels. Treatment of aortic cultures with angiopoietin-1 (Ang-1), an angiogenic factor implicated in vascular maturation and remodeling, stimulates the mural cell recruitment process. Ang-1 induces expression of many cytokines and chemokines including monocyte chemotactic protein-1 (MCP-1). Inhibition of p38 MAP kinase, a signaling molecule required for mural cell recruitment, blocks Ang1-induced MCP-1 expression. Recombinant MCP-1 dose-dependently increases mural cell number while an anti-MCP-1 blocking antibody reduces it. In addition, antibody mediated neutralization of MCP-1 abrogates the stimulatory effect of Ang-1 on mural cell recruitment. Aortic rings from genetically modified mice deficient in MCP-1 or its receptor CCR2 have fewer mural cells than controls. MCP-1 deficiency also impairs the mural cell recruitment activity of Ang-1. Our studies indicate that spontaneous and Ang1-induced mural cell recruitment in the aortic ring of model of angiogenesis are in part mediated by MCP-1. These results implicate MCP-1 as one of the mediators of mural cell recruitment in the aortic ring model, and suggest that chemokine pathways may contribute to the assembly of the vessel wall during the angiogenesis response to injury.

  17. Elevated bronchoalveolar concentrations of MCP-1 in patients with pulmonary alveolar proteinosis.

    Science.gov (United States)

    Iyonaga, K; Suga, M; Yamamoto, T; Ichiyasu, H; Miyakawa, H; Ando, M

    1999-08-01

    Pulmonary alveolar proteinosis (PAP) is a rare disease of unknown aetiology characterized by accumulations of lipoproteinaceous material within the alveoli. The alveolar macrophages become increasingly foamy, and are thought to have a role in the pathogenesis of PAP. However, the mechanisms of macrophage recruitment are unclear. In the bronchoalveolar lavage fluid (BALF) of four patients with PAP and 20 normal control subjects, the following were examined: the monocyte chemotactic activity due to the chemokine monocyte chemoattractant protein (MCP)-1 with the use of a chemotactic chamber assay, the levels of MCP-1 by enzyme-linked immunosorbent assay, and the MCP-1 expression on lavage cells by immunocytochemistry and in situ hybridization. The monocyte chemotactic activity in the BALF of the PAP patients was markedly elevated, and the activity was completely absorbed by treatment with anti-MCP-1. The MCP-1 levels in the BALF were surprisingly high in the PAP group (25,100+/-472 pg x mL(-1)), whereas low levels of MCP-1 were detected in the normal control subjects (mean: never smokers 4.8; smokers 10.4 pg x mL(-1)). MCP-1 protein and messenger ribonucleic acid were expressed by macrophages from the PAP patients, and the expression was reduced according to foaming of the cells; there were monocyte-like macrophages with strong expression, small foamy cells with moderate expression, large foamy cells with a faint expression of MCP-1, and ghost cells with no expression. However, the increase of macrophage number in the PAP BALF was relatively small. These data suggest that monocyte chemoattractant protein(-1) expression by alveolar macrophages represents an amplification mechanism for the recruitment of additional macrophages to the alveoli in pulmonary alveolar proteinosis. It is possible that an ingestion of an excess of alveolar materials in pulmonary alveolar proteinosis may impair the macrophage function and the survival, resulting in the lack of a prominent

  18. Lysophosphatidic Acid Stimulates MCP-1 Secretion from C2C12 Myoblast

    OpenAIRE

    Tamotsu Tsukahara; Hisao Haniu

    2012-01-01

    Chemokines are regulatory proteins that play an important role in muscle cell migration and proliferation. In this study, C2C12 cells treated with lysophosphatidic acid (LPA) showed an increase in endogenous monocyte chemotactic protein-1 (MCP-1) expression and secretion. LPA is a naturally occurring bioactive lysophospholipid with hormone- and growth-factor-like activities. LPA is produced by activated platelets, cytokine-stimulated leukocytes, and possibly by other cell types. However, the ...

  19. Expression of monocyte chemoattractant protein-1 in IgA nephropathy and its significance%IgA 肾病患者肾脏 MCP-1的表达及意义

    Institute of Scientific and Technical Information of China (English)

    钱白音; 吴锡信; 麦美芳; 张桦; 李中和; 崔彤霞

    2014-01-01

    Objective To evaluate the role of monocyte chemoattractant protein-1(MCP-1) in the mechanism of pro-gression of IgA nephropathy.Methods A total of 34 patients with biopsy proven IgA nephropathy were studied.The ex-pression of MCP-1 in renal tissues were detected by immunohistochemical staining method; the levels of serum creatinine ( Scr) were examined by sarcosine oxidase method;MCP-1 expression in renal tissue in patients with different degree of tu-bulointerstitial lesions and different levels of Scr were compared.Molecular weight of urinary protein were detected by sodi-um dodecyl sulfate-polyacrylamide gel electrophoresis( SDS-PAGE) , and were further typed;MCP-1 expression in renal tis-sue in patients with different molecular weight of urinary protein were compared.And the relationship between the MCP-1 expression and the twenty-four-hour urine protein quantitation in patients with IgA nephropathy was analyzed by pearson cor-relation analysis.Results MCP-1 expression was mainly in renal tubular epithelial cells of IgA nephropathy patients, and was in positive correlation to twenty-four-hour urine protein quantitation (r=0.34,P140μmol/L group than Scr≤140μmol/L group (P<0.05), and was significantly higher in 10 kD proteinuria group than 23 kD proteinuria group (P<0.05).Conclusion MCP-1 may play an important role in the progression of IgA nephropathy.Low molecular weight urinary protein such as 10 kD protein may have close relationship with the expression of MCP-1 in renal tissue of IgA nephropathy.%目的:观察IgA肾病患者肾脏单核细胞趋化蛋白-1(MCP-1)表达变化,并探讨其作用。方法用免疫组织化学染色法检测34例同步行肾活检诊断明确的IgA肾病患者肾脏MCP-1表达,用肌氨酸氧化酶法检测血清肌酐( Scr),比较不同程度肾小管间质病变及不同血清肌酐水平患者MCP-1的差异。用SDS-PAGE法检测尿蛋白分子量,并进一步分型,对不同分子量尿蛋白患者的MCP

  20. Plasma monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha are increased in patients with polycystic ovary syndrome (PCOS) and associated with adiposity, but unaffected by pioglitazone treatment

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Andersen, Marianne; Richelsen, Bjørn;

    2009-01-01

    OBJECTIVE: Hirsutism is most often caused by polycystic ovary syndrome (PCOS). PCOS patients are characterized by insulin resistance, abdominal obesity and low-grade inflammation. Insulin sensitizing treatment reduces the inflammatory state, but the effect on serum levels of migration inhibitor...... factor (MIF), monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-1alpha have not been evaluated before in PCOS. RESEARCH DESIGN AND METHODS: Plasma chemokine levels (MCP-1, MIP-1alpha and MIF) were measured in two study designs. (i) 51 hirsute patients and 63 matched...... controls and (ii) 30 PCOS patients before and after randomized treatment with 30 mg pioglitazone/placebo for 16 weeks. Clinical evaluations and whole body DXA-scans were performed in all participants. RESULTS: Hirsute patients (n = 51) had significantly increased MCP-1 [121 (15-950) vs. 81 (18-365) pg...

  1. Lysophosphatidic Acid Stimulates MCP-1 Secretion from C2C12 Myoblast.

    Science.gov (United States)

    Tsukahara, Tamotsu; Haniu, Hisao

    2012-01-01

    Chemokines are regulatory proteins that play an important role in muscle cell migration and proliferation. In this study, C2C12 cells treated with lysophosphatidic acid (LPA) showed an increase in endogenous monocyte chemotactic protein-1 (MCP-1) expression and secretion. LPA is a naturally occurring bioactive lysophospholipid with hormone- and growth-factor-like activities. LPA is produced by activated platelets, cytokine-stimulated leukocytes, and possibly by other cell types. However, the LPA analog cyclic phosphatidic acid (cPA) had no effect on the expression and secretion of MCP-1. LPA, although similar in structure to cPA, had potent inducing effects on MCP-1 expression in C2C12 cells. In this study, we showed that LPA enhanced MCP-1 mRNA expression and protein secretion in a dose-dependent manner. Taken together, these results suggest that LPA enhances MCP-1 secretion in C2C12 cells and thus may play an important role in cell proliferation. PMID:24049655

  2. Intelectin is required for IL-13-induced monocyte chemotactic protein-1 and -3 expression in lung epithelial cells and promotes allergic airway inflammation

    OpenAIRE

    Gu, Naibing; Kang, Guannan; Jin, Chang'E; Xu, Yongjian; ZHANG, ZHENXIANG; Erle, David J.; Zhen, Guohua

    2009-01-01

    Asthma is characterized by airway inflammation, mucus overproduction, airway hyperreactivity, and peribronchial fibrosis. Intelectin has been shown to be increased in airway epithelium of asthmatics. However, the role of intelectin in the pathogenesis of asthma is unknown. Airway epithelial cells can secrete chemokines such as monocyte chemotactic protein (MCP)-1 and -3 that play crucial roles in asthmatic airway inflammation. We hypothesized that intelectin plays a role in allergic airway in...

  3. MCP -1在妊娠期高血压疾病患者血清中的变化及意义%Expression and significance of the monocyte chemoattractant protein - 1 in serum from patients with hypertensive disorder complicating pregnancy

    Institute of Scientific and Technical Information of China (English)

    何晓宇; 林晶; 许波

    2012-01-01

    目的 探讨妊娠期高血压疾病患者血清单核细胞趋化蛋白-1 (MCP-1)变化的意义.方法 用ELISA法对21例妊娠期高血压疾病患者(其中轻度子痫前期12例,重度子痫前期9例)血清MCP -1浓度进行测定,并选择同期30例正常孕妇作为对照组.结果 妊娠期高血压疾病患者血清中MCP -1含量显著高于对照组孕妇,并随病情加重呈增加趋势.结论 MCP -1所参与的免疫反应可能是妊娠期高血压疾病的发病机制之一.%Objective: To explore the clinical significance of changes of monocyte chemoattractant protein - 1 (MCP - 1) in patients with hypertensive disorder complicating pregnancy. Methods: EliSA was used to measure the levels mcp - 1 in maternal serumof 21 patients with hypertensive disorder complicating pregnancy (study group) and 30 normal pregnancies (control group). The study group was further divided into two groups; mild preeclampsia pations (12 cases) and severe preeclampsia patients (9 cases). Results ; The levels mcp -1 in serum of patients with hypertensive disorder complicating pregnancy had a increasing trend as hypertensive disorder complicating pregnancy degree elevated. Conclusion: MCP -1 participation in the immune response is possibly one of mechanisms of disease incidence.

  4. ROCK inhibitor fasudil attenuated high glucose-induced MCP-1 and VCAM-1 expression and monocyte-endothelial cell adhesion

    Directory of Open Access Journals (Sweden)

    Li Hailing

    2012-06-01

    Full Text Available Abstract Background Previous studies suggested that the RhoA/ROCK pathway may contribute to vascular complications in diabetes. The present study was designed to investigate whether ROCK inhibitor fasudil could prevent high glucose-induced monocyte-endothelial cells adhesion, and whether this was related to fasudil effects on vascular endothelial cell expression of chemotactic factors, vascular cell adhesion molecule-1 (VCAM-1 and monocyte chemoattractant protein-1 (MCP-1. Methods HUVECs were stimulated with high glucose (HG or HG + fasudil in different concentration or different time. Monocyte-endothelial cell adhesion was determined using fluorescence-labeled monocytes. The mRNA and protein expression of VCAM-1 and MCP-1 were measured using real-time PCR and western blot. The protein levels of RhoA, ROCKI and p-MYPT were determined using western blot analysis. ELISA was employed to measure the expression of soluble VCAM-1 and MCP-1 in cell supernatants and human serum samples. Results Fasudil significantly suppressed HG-induced adhesion of THP-1 to HUVECs. Fasudil reduced Rho/ROCK activity (as indicated by lower p-MYPT/MYPT ratio, and prevented HG induced increases in VCAM-1 and MCP-1 mRNA and protein levels. Fasudil also decreased MCP-1 concentration in HUVEC supernatants, but increased sVCAM-1 shedding into the media. In human diabetic subjects, 2 weeks of fasudil treatment significantly decreased serum MCP-1 level from 27.9 ± 10.6 pg/ml to 13.8 ± 7.0 pg/ml (P P  Conclusions Treatment with the Rho/ROCK pathway inhibitor fasudil attenuated HG-induced monocyte-endothelial cell adhesion, possibly by reducing endothelial expression of VCAM-1 and MCP-1. These results suggest inhibition of Rho/ROCK signaling may have therapeutic potential in preventing diabetes associated vascular inflammation and atherogenesis.

  5. FGFR3 promotes angiogenesis-dependent metastasis of hepatocellular carcinoma via facilitating MCP-1-mediated vascular formation.

    Science.gov (United States)

    Liu, Xinyu; Jing, Xiaoqian; Cheng, Xi; Ma, Ding; Jin, Zhijian; Yang, Weiping; Qiu, Weihua

    2016-05-01

    The biological role of fibroblast growth factor receptor 3 (FGFR3) in tumor angiogenesis of hepatocellular carcinoma (HCC) has not been discussed before. Our previous work had indicated FGFR3 was overexpressed in HCC, and silencing FGFR3 in Hu7 cells could regulate tumorigenesis via down-regulating the phosphorylation level of key members of classic signaling pathways including ERK and AKT. In the present work, we explored the role of FGFR3 in angiogenesis-dependent metastasis by using SMMC-7721 and QGY-7703 stable cell lines. Our results indicated FGFR3 could regulate in vitro cell migration ability and in vivo lung metastasis ability of HCC, which was in accordance with increased angiogenesis ability in vitro and in vivo. Using the supernatant from SMMC-7721/FGFR3 cells, we conducted a human angiogenesis protein microarray including 43 angiogenesis factors and found that FGFR3 modulated angiogenesis and metastasis of HCC mainly by promoting the protein level of monocyte chemotactic protein 1 (MCP-1). Silencing FGFR3 by short hairpin RNA (shRNA) could reduce MCP-1 level in lysates and supernatant of QGY-7703 cells and SMMC-7721 cells. Silencing MCP-1 in QGY-7703 or SMMC-7721 cells could induce similar phenotypes compared with silencing FGFR3. Our results suggested FGFR3 promoted metastasis potential of HCC, at least partially if not all, via facilitating MCP-1-mediated angiogenesis, in addition to previously found cell growth and metastasis. MCP-1, a key medium between HCC cells and HUVECs, might be a novel anti-vascular target in HCC. PMID:27044356

  6. Mechanism and role of MCP-1 upregulation upon chikungunya virus infection in human peripheral blood mononuclear cells

    NARCIS (Netherlands)

    Ruiz Silva, Mariana; van der Ende-Metselaar, Heidi; Mulder, H Lie; Smit, Jolanda M; Rodenhuis-Zybert, Izabela A

    2016-01-01

    Monocyte chemoattractant protein-1 (MCP-1/CCL2)-mediated migration of monocytes is essential for immunological surveillance of tissues. During chikungunya virus (CHIKV) infection however, excessive production of MCP-1 has been linked to disease pathogenesis. High MCP-1 serum levels are detected duri

  7. MCP-1 expressed by osteoclasts stimulates osteoclastogenesis in an autocrine/paracrine manner

    Energy Technology Data Exchange (ETDEWEB)

    Miyamoto, Kana [Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Division of Orthopedic Research, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Ninomiya, Ken [Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Sonoda, Koh-Hei [Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582 (Japan); Miyauchi, Yoshiteru; Hoshi, Hiroko [Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Division of Orthopedic Research, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Iwasaki, Ryotaro [Division of Orthopedic Research, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Department of Dentistry and Oral Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Miyamoto, Hiroya [Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Division of Orthopedic Research, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); and others

    2009-06-05

    Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that plays a critical role in the recruitment and activation of leukocytes. Here, we describe that multinuclear osteoclast formation was significantly inhibited in cells derived from MCP-1-deficient mice. MCP-1 has been implicated in the regulation of osteoclast cell-cell fusion; however defects of multinuclear osteoclast formation in the cells from mice deficient in DC-STAMP, a seven transmembrane receptor essential for osteoclast cell-cell fusion, was not rescued by recombinant MCP-1. The lack of MCP-1 in osteoclasts resulted in a down-regulation of DC-STAMP, NFATc1, and cathepsin K, all of which were highly expressed in normal osteoclasts, suggesting that osteoclast differentiation was inhibited in MCP-1-deficient cells. MCP-1 alone did not induce osteoclastogenesis, however, the inhibition of osteoclastogenesis in MCP-1-deficient cells was restored by addition of recombinant MCP-1, indicating that osteoclastogenesis was regulated in an autocrine/paracrine manner by MCP-1 under the stimulation of RANKL in osteoclasts.

  8. Autocrine MCP-1/CCR2 signaling stimulates proliferation and migration of renal carcinoma cells

    Science.gov (United States)

    Küper, Christoph; Beck, Franz-Xaver; Neuhofer, Wolfgang

    2016-01-01

    The chemokine monocyte chemoattractant protein-1 [MCP-1; also known as chemokine (C-C motif) ligand 2] is an important mediator of monocyte recruitment during inflammatory processes. Pathologically high expression levels of MCP-1 by tumor cells have been observed in a variety of cancer types. In the majority of cases, high MCP-1 expression is associated with a poor prognosis, as infiltration of the tumor with inflammatory monocytes promotes tumor progression and metastasis. MCP-1 is also expressed in renal cell carcinoma (RCC). In the present study, the function and the regulation of MCP-1 was investigated in two RCC cell lines, CaKi-1 and 786-O. In both cell lines, expression of MCP-1 was significantly enhanced compared with non-cancerous control cells. As expected, secretion of MCP-1 into the medium facilitated the recruitment of peripheral blood monocytes via the chemokine (C-C motif) receptor type 2 (CCR2). As expression of CCR2 was also detected in 786-O and CaKi-1 cells, the effect of autocrine MCP-1/CCR2 signaling was evaluated in these cells. In proliferation assays, administration of an MCP-1 neutralizing antibody or of a CCR2 antagonist to CaKi-1 and 786-O cells significantly decreased cell growth; supplementation of the growth medium with recombinant human MCP-1 had no additional effect on proliferation. The migration ability of RCC cells was impaired by MCP-1 neutralization or pharmacological CCR2 inhibition, while it was stimulated by the addition of recombinant human MCP-1, compared with untreated control cells. Finally, substantial differences in the regulation of MCP-1 expression were observed between RCC cell lines. In CaKi-1 cells, expression of MCP-1 appears to be largely mediated by the transcription factor nuclear factor of activated T cells 5, while in 786-O cells, deletion of the tumor suppressor gene Von-Hippel-Lindau appeared to be responsible for MCP-1 upregulation, as suggested by previous studies. Taken together, the results of the

  9. Cardiac Stem Cell Secretome Protects Cardiomyocytes from Hypoxic Injury Partly via Monocyte Chemotactic Protein-1-Dependent Mechanism.

    Science.gov (United States)

    Park, Chi-Yeon; Choi, Seung-Cheol; Kim, Jong-Ho; Choi, Ji-Hyun; Joo, Hyung Joon; Hong, Soon Jun; Lim, Do-Sun

    2016-01-01

    Cardiac stem cells (CSCs) were known to secrete diverse paracrine factors leading to functional improvement and beneficial left ventricular remodeling via activation of the endogenous pro-survival signaling pathway. However, little is known about the paracrine factors secreted by CSCs and their roles in cardiomyocyte survival during hypoxic condition mimicking the post-myocardial infarction environment. We established Sca-1+/CD31- human telomerase reverse transcriptase-immortalized CSCs (Sca-1+/CD31- CSCs(hTERT)), evaluated their stem cell properties, and paracrine potential in cardiomyocyte survival during hypoxia-induced injury. Sca-1+/CD31- CSCs(hTERT) sustained proliferation ability even after long-term culture exceeding 100 population doublings, and represented multi-differentiation potential into cardiomyogenic, endothelial, adipogenic, and osteogenic lineages. Dominant factors secreted from Sca-1+/CD31- CSCs(hTERT) were EGF, TGF-β1, IGF-1, IGF-2, MCP-1, HGF R, and IL-6. Among these, MCP-1 was the most predominant factor in Sca-1+/CD31- CSCs(hTERT) conditioned medium (CM). Sca-1+/CD31- CSCs(hTERT) CM increased survival and reduced apoptosis of HL-1 cardiomyocytes during hypoxic injury. MCP-1 silencing in Sca-1+/CD31- CSCs(hTERT) CM resulted in a significant reduction in cardiomyocyte apoptosis. We demonstrated that Sca-1+/CD31- CSCs(hTERT) exhibited long-term proliferation capacity and multi-differentiation potential. Sca-1+/CD31- CSCs(hTERT) CM protected cardiomyocytes from hypoxic injury partly via MCP-1-dependent mechanism. Thus, they are valuable sources for in vitro and in vivo studies in the cardiovascular field. PMID:27231894

  10. The expression of monocyte chemoattractant protein 1 and RANTES and their significance in the pathogenesis of chronic renal allograft dysfunction%MCP-1、RANTES在慢性移植肾失功肾组织中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    李晏强; 罗皓; 邹和群; 眭维国; 王保瑶; 邹贵勉

    2012-01-01

    目的 探讨单核细胞趋化蛋白-1(MCP-1)和RANTES在慢性移植肾失功(CRAD)患者移植肾组织中的表达及意义.方法 用免疫组织化学技术和计算机真彩色图像分析系统半定量检测32例慢性移植肾失功患者移植肾组织中MCP-1和RANTES的表达,分析与移植肾间质纤维化/小管萎缩程度及炎性细胞浸润程度之间的关系.结果 慢性移植肾失功患者的移植肾组织中MCP-1和RANTES的表达较正常肾组织中明显增加,并随着间质纤维化/小管萎缩及炎症细胞浸润程度而递增.结论 移植肾组织中MCP-1和RANTES的表达升高与慢性移植肾失功的进展有关.%Objective To in vestige the expression of monocyte chemoattractant protein 1 (MCP-l) and RANTES and their significance in the pathogenesis of chronic renal allograft dy sfunction.Method Immunohistochemical assay and computer-assisted genuine colored image analysis system were used to detect the expression of MCP-l and RANTES in the renal allografts of patients with CARD. The relationship between expression level of mcp-land Rantes and either the grade of inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft was analyzed.Six specimens of healthy renal tissue were used as controls. Results The expressions levels of MCP-l and RANTES were significantly higher in the renal tissues of the patients, compared to normal renal tissues, and the expressions tended to increase with the pathological grades of either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft tissue.Conclusion The up-regulated expression of MCP-l and Rantes in transplant kidney tissue may have the relationship win the progressive of the chronic renal allograft dysfunction

  11. Effect of propofol pretreatment on hippocampal monocyte chemotactic protein-1 and CC-chemokine receptor type 2 expression following forebrain ischemia-reperfusion in rats%异丙酚预先给药对大鼠前脑缺血再灌注时海马单核细胞趋化因子1及其受体表达的影响

    Institute of Scientific and Technical Information of China (English)

    郭永清; 侯晓来; 刘友章; 张华萍; 郭政

    2011-01-01

    Objective To investigate the effect of propofol pretreatment on hippocampal monocyte chemotactic protein-1 ( MCP-1 ) and CC-chemokine receptor type 2 (CCR2) expression following forebrain ischemiarepcrfusion (I/R) in rats. Methods Twenty-four male SD rats weighing 250-300 g were randomly divided into 3 groups ( n = 8 each): group Ⅰ control; group Ⅱ I/R and group Ⅲ propofol pretreatment. Cerebral I/R was induced by clamping bilateral common carotid arteries for 10 min combined with hypotension ( MAP was maintained at 35-45 mm Hg) induced by exsanguinations in group Ⅱ and Ⅲ. In group Ⅲ propofol 50 mg/kg was injected into femoral vein immediately before cerebral ischemia. The animals were sacrificed at 6 h of reperfusion. Hippocampal tissue was obtained for detection of MCP-1 mRNA and CCR2 mRNA and their protein expression by RT-PCR and Western blot technique. Results I/R significantly increased the expression of MCP-1 and CCR2 in hippoeampal tissue as compared with control group. Propofol pretreatment significantly attenuated cerebral I/R induced increase in MCP-1 and CCR2 expression. Conclusion Propofol pretreatment can significantly inhibit forebrain I/R-induced hippocampal MCP-1 and CCP2 expression.%目的 探讨异丙酚预先给药对大鼠前脑缺血再灌注时海马单核细胞趋化因子1(MCP1)及其受体(CCR2)表达的影响.方法 健康成年雄性SD大鼠24只,体重250~300g,随机分为3组(n=8):假手术组(S组)仅暴露双侧颈总动脉及股动静脉置管,不夹闭;缺血再灌注组(IR组)采用夹闭双侧颈总动脉10 min合并放血降压再回输法制备前脑缺血再灌注损伤模型;异丙酚预先给药组(P组)脑缺血前即刻股静脉注射异丙酚50 mg/kg.于再灌注6 h时处死大鼠取脑,分离海马神经元,采用RT-PCR法测定MCP-1 mRNA和CCR2mRNA的表达,Western blot法测定MCP-1和CCR2蛋白的表达.结果 IR组和P组海马神经元MCP-1及CCR2表达较S组上调(P<0.05);P组海马神经元MCP-1

  12. MCP-1 binds to oxidized LDL and is carried by lipoprotein(a) in human plasma

    Science.gov (United States)

    Wiesner, Philipp; Tafelmeier, Maria; Chittka, Dominik; Choi, Soo-Ho; Zhang, Li; Byun, Young Sup; Almazan, Felicidad; Yang, Xiaohong; Iqbal, Navaid; Chowdhury, Punam; Maisel, Alan; Witztum, Joseph L.; Handel, Tracy M.; Tsimikas, Sotirios; Miller, Yury I.

    2013-01-01

    Lipoprotein oxidation plays an important role in pathogenesis of atherosclerosis. Oxidized low density lipoprotein (OxLDL) induces profound inflammatory responses in vascular cells, such as production of monocyte chemoattractant protein-1 (MCP-1) [chemokine (C-C motif) ligand 2], a key chemokine in the initiation and progression of vascular inflammation. Here we demonstrate that OxLDL also binds MCP-1 and that the OxLDL-bound MCP-1 retains its ability to recruit monocytes. A human MCP-1 mutant in which basic amino acids Arg-18 and Lys-19 were replaced with Ala did not bind to OxLDL. The MCP-1 binding to OxLDL was inhibited by the monoclonal antibody E06, which binds oxidized phospholipids (OxPLs) in OxLDL. Because OxPLs are carried by lipoprotein(a) [Lp(a)] in human plasma, we tested to determine whether Lp(a) binds MCP-1. Recombinant wild-type but not mutant MCP-1 added to human plasma bound to Lp(a), and its binding was inhibited by E06. Lp(a) captured from human plasma contained MCP-1 and the Lp(a)-associated endogenous MCP-1 induced monocyte migration. These results demonstrate that OxLDL and Lp(a) bind MCP-1 in vitro and in vivo and that OxPLs are major determinants of the MCP-1 binding. The association of MCP-1 with OxLDL and Lp(a) may play a role in modulating monocyte trafficking during atherogenesis. PMID:23667177

  13. PEG-albumin plasma expansion increases expression of MCP-1 evidencing increased circulatory wall shear stress: an experimental study.

    Directory of Open Access Journals (Sweden)

    C Makena Hightower

    Full Text Available Treatment of blood loss with plasma expanders lowers blood viscosity, increasing cardiac output. However, increased flow velocity by conventional plasma expanders does not compensate for decreased viscosity in maintaining vessel wall shear stress (WSS, decreasing endothelial nitric oxide (NO production. A new type of plasma expander using polyethylene glycol conjugate albumin (PEG-Alb causes supra-perfusion when used in extreme hemodilution and is effective in treating hemorrhagic shock, although it is minimally viscogenic. An acute 40% hemodilution/exchange-transfusion protocol was used to compare 4% PEG-Alb to Ringer's lactate, Dextran 70 kDa and 6% Hetastarch (670 kDa in unanesthetized CD-1 mice. Serum cytokine analysis showed that PEG-Alb elevates monocyte chemotactic protein-1 (MCP-1, a member of a small inducible gene family, as well as expression of MIP-1α, and MIP-2. MCP-1 is specific to increased WSS. Given the direct link between increased WSS and production of NO, the beneficial resuscitation effects due to PEG-Alb plasma expansion appear to be due to increased WSS through increased perfusion and blood flow rather than blood viscosity.

  14. Sulforaphane inhibits de novo synthesis of IL-8 and MCP-1 in human epithelial cells generated by cigarette smoke extract.

    Science.gov (United States)

    Starrett, Warren; Blake, David J

    2011-06-01

    Chronic obstructive pulmonary disease (COPD) is currently the fifth leading cause of death worldwide. Exposure to cigarette smoke (CS) is the primary factor associated with the COPD development. CS activates epithelial cells to secrete chemokines such as interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) that recruit neutrophils and macrophages to the lung. These inflammatory cells then release additional chemokines and cytokines leading to chronic inflammation that initiates apoptosis in epithelial and endothelial cells and destruction of alveolar structure. Pulmonary epithelium responds to oxidative stress mediated by CS through activating NRF2-dependent pathways, leading to an increased expression of antioxidant and cytoprotective enzymes thereby providing a protective response against CS-induced lung injury. We hypothesized that activating NRF2-dependent cytoprotective gene expression with sulforaphane (SFN) affords protection against CS-induced lung damage by inhibiting chemokine production. Results indicate that in the human BEAS-2B epithelial cell line, 5 μM SFN activated NRF2-dependent gene expression by triggering the translocation of NRF2 to the nucleus and significantly increased the expression of NRF2-dependent genes such as NADPH quinone oxidoreductase-1, heme oxygenase-1, and glutamate cysteine ligase modulatory subunit. Cigarette smoke extract (CSE) exposure of BEAS-2B cells significantly increased production of both IL-8 and MCP-1. Production of both chemokines was significantly reduced with SFN given prior to CSE; SFN inhibited IL-8 and MCP-1 gene expression at the transcription level. Our results indicate that activating NRF2 pathways with SFN inhibits CSE-induced chemokine production in human epithelial cells. However, the mechanism by which the production of chemokines is inhibited through SFN still remains to be elucidated. SFN may enhance NRF2 transcriptional activity resulting in the inhibition of proinflammatory pathways such

  15. 球形脂联素抑制高糖环境下肾小管上皮细胞单核趋化蛋白-1的高表达%Global adiponectin suppress the high expression of monocyte chemotactic protein-1 induced by high glucose in NRK52E cells

    Institute of Scientific and Technical Information of China (English)

    姚涛; 吴小燕; 於文丽; 高苹; 吴屹哲

    2015-01-01

    Objective To investigate the effect of globular adiponectin on the high expression of monocyte chemotactic protein-1 (MCP-1) induced by high glucose in rat renal tubular epithelial cells (NRK52E),and its relationship with adiponectin receptors and p38MAPK.Methods NRK52E cells were cultured in vitro and divided into six groups:normal glucose group (NG,5.6 mmol/L glucose),high glucose group(HG,25 mmol/L glucose),gAd groupl (HG+gAd 2 mg/L),gAd group2 (HG+gAd 5 mg/L),gAd group3 (HG+gAd 10 mg/L),p38MAPK antagonist group:(SB,HG+SB203580 10 μmol/L).The protein expression of phosphorylated p38MAPK (p-p38MAPK),total p38MAPK (t-p38MAPK),MCP-1 and AdipoR1/AdipoR2 were examined by western blotting.The mRNA expression of MCP-1 and AdipoR1/AdipoR2 were detected by RT-PCR and real-time PCR respectively.Results Compared with NG group,the mRNA and protein expression of MCP-1 increased significantly in HG group (all P< 0.05).The phosphorylation of p38MAPK increased (P< 0.05) with no change in t-p38MAPK protein.The addition of gAd or SB203580 inhibited the unregulation of MCP-1 and p-p38MAPK induced by HG.Two kinds of adipoR,adipoR1 and adipoR2,were all detectable in NG group,and mRNA and protein expression of adipoR1 was higher than that of adipoR2 (P< 0.01).Compared with NG group,the expression of adipoR decreased in HG group,but the difference had no statistical significance(P > 0.05).Compared to HG group,the mRNA and protein expression of adipoR1 increased in gAd groups (all P < 0.01).Conclusion The gAd can dose-dependently attenuate the overexpression of MCP-1 induced by high glucose,and this protective effect may be mediated by adipoR1 and p38MAPK.%目的 探讨高糖环境下球形脂联素(globular adiponectin,gAd)对大鼠近端肾小管上皮细胞(NRK-52E)单核趋化蛋白-1 (MCP-1)表达的影响以及其与脂联素受体(AdipoR)、p38丝裂原活化蛋白激酶(p38MAPK)的关系.方法 体外培养NRK-52E细胞,分为六组:正常对照组(NG,5.6 mmol

  16. Mechanism and role of MCP-1 upregulation upon chikungunya virus infection in human peripheral blood mononuclear cells

    Science.gov (United States)

    Ruiz Silva, Mariana; van der Ende-Metselaar, Heidi; Mulder, H. Lie; Smit, Jolanda M.; Rodenhuis-Zybert, Izabela A.

    2016-01-01

    Monocyte chemoattractant protein-1 (MCP-1/CCL2)-mediated migration of monocytes is essential for immunological surveillance of tissues. During chikungunya virus (CHIKV) infection however, excessive production of MCP-1 has been linked to disease pathogenesis. High MCP-1 serum levels are detected during the viremic phase of CHIKV infection and correlate with the virus titre. In vitro CHIKV infection was also shown to stimulate MCP-1 production in whole blood; yet the role and the mechanism of MCP-1 production upon infection of human peripheral blood mononuclear cells remain unknown. Here we found that active CHIKV infection stimulated production of MCP-1 in monocytes. Importantly however, we found that communication with other leukocytes is crucial to yield MCP-1 by monocytes upon CHIKV infection. Indeed, blocking interferon-α/β receptor or the JAK1/JAK2 signalling downstream of the receptor abolished CHIKV-mediated MCP-1 production. Additionally, we show that despite the apparent correlation between IFN type I, CHIKV replication and MCP-1, modulating the levels of the chemokine did not influence CHIKV infection. In summary, our data disclose the complexity of MCP-1 regulation upon CHIKV infection and point to a crucial role of IFNβ in the chemokine secretion. We propose that balance between these soluble factors is imperative for an appropriate host response to CHIKV infection. PMID:27558873

  17. Mechanism and role of MCP-1 upregulation upon chikungunya virus infection in human peripheral blood mononuclear cells.

    Science.gov (United States)

    Ruiz Silva, Mariana; van der Ende-Metselaar, Heidi; Mulder, H Lie; Smit, Jolanda M; Rodenhuis-Zybert, Izabela A

    2016-01-01

    Monocyte chemoattractant protein-1 (MCP-1/CCL2)-mediated migration of monocytes is essential for immunological surveillance of tissues. During chikungunya virus (CHIKV) infection however, excessive production of MCP-1 has been linked to disease pathogenesis. High MCP-1 serum levels are detected during the viremic phase of CHIKV infection and correlate with the virus titre. In vitro CHIKV infection was also shown to stimulate MCP-1 production in whole blood; yet the role and the mechanism of MCP-1 production upon infection of human peripheral blood mononuclear cells remain unknown. Here we found that active CHIKV infection stimulated production of MCP-1 in monocytes. Importantly however, we found that communication with other leukocytes is crucial to yield MCP-1 by monocytes upon CHIKV infection. Indeed, blocking interferon-α/β receptor or the JAK1/JAK2 signalling downstream of the receptor abolished CHIKV-mediated MCP-1 production. Additionally, we show that despite the apparent correlation between IFN type I, CHIKV replication and MCP-1, modulating the levels of the chemokine did not influence CHIKV infection. In summary, our data disclose the complexity of MCP-1 regulation upon CHIKV infection and point to a crucial role of IFNβ in the chemokine secretion. We propose that balance between these soluble factors is imperative for an appropriate host response to CHIKV infection. PMID:27558873

  18. NFAT5 Contributes to Osmolality-Induced MCP-1 Expression in Mesothelial Cells

    Directory of Open Access Journals (Sweden)

    Christoph Küper

    2012-01-01

    Full Text Available Increased expression of the C-C chemokine monocyte chemoattractant protein-1 (MCP-1 in mesothelial cells in response to high glucose concentrations and/or high osmolality plays a crucial role in the development of peritoneal fibrosis during continuous ambulatory peritoneal dialysis (CAPD. Recent studies suggest that in kidney cells osmolality-induced MCP-1 upregulation is mediated by the osmosensitive transcription factor, nuclear factor of activated T cells 5 (NFAT5. The present study addressed the question of whether activation of NFAT5 by hyperosmolality, as present in PD fluids, contributes to MCP-1 expression in the mesothelial cell line Met5A. Hyperosmolality, induced by addition of glucose, NaCl, or mannitol to the growth medium, increased NFAT5 activity and stimulated MCP-1 expression in Met5A cells. siRNA-mediated knockdown of NFAT5 attenuated osmolality-induced MCP-1 upregulation substantially. Hyperosmolality also induced activation of nuclear factor-κB (NF-κB. Accordingly, pharmacological inhibition of NF-κB significantly decreased osmolality-induced MCP-1 expression. Taken together, these results indicate that high osmolalities activate the transcription factor NFAT5 in mesothelial cells. NFAT5 in turn upregulates MCP-1, likely in combination with NF-κB, and thus may participate in the development of peritoneal fibrosis during CAPD.

  19. Exosomes derived from MSCs ameliorate retinal laser injury partially by inhibition of MCP-1

    Science.gov (United States)

    Yu, Bo; Shao, Hui; Su, Chang; Jiang, Yuanfeng; Chen, Xiteng; Bai, Lingling; Zhang, Yan; Li, Qiutang; Zhang, Xiaomin; Li, Xiaorong

    2016-01-01

    Although accumulated evidence supports the notion that mesenchymal stem cells (MSCs) act in a paracrine manner, the mechanisms are still not fully understood. Recently, MSC-derived exosomes (MSC-Exos), a type of microvesicle released from MSCs, were thought to carry functional proteins and RNAs to recipient cells and play therapeutic roles. In the present study, we intravitreally injected MSCs derived from either mouse adipose tissue or human umbilical cord, and their exosomes to observe and compare their functions in a mouse model of laser-induced retinal injury. We found that both MSCs and their exosomes reduced damage, inhibited apoptosis, and suppressed inflammatory responses to obtain better visual function to nearly the same extent in vivo. Obvious down-regulation of monocyte chemotactic protein (MCP)-1 in the retina was found after MSC-Exos injection. In vitro, MSC-Exos also down-regulated MCP-1 mRNA expression in primarily cultured retinal cells after thermal injury. It was further demonstrated that intravitreal injection of an MCP-1-neutralizing antibody promoted the recovery of retinal laser injury, whereas the therapeutic effect of exosomes was abolished when MSC-Exos and MCP-1 were administrated simultaneously. Collectively, these results suggest that MSC-Exos ameliorate laser-induced retinal injury partially through down-regulation of MCP-1. PMID:27686625

  20. 西洛他唑联合替米沙坦对早期2型糖尿病肾病血清单核细胞趋化蛋白1和可溶性细胞间黏附分子1的影响%The Effect of Cilostazol Combined with Telmisartan on Serum Monocyte Chemotactic Protein-1 and Soluble Intercellu-lar Adhesion Molecule-1 in Early Type 2 Diabetic Nephropathy

    Institute of Scientific and Technical Information of China (English)

    焦秀敏; 武晋晓; 陈彬; 袁涛; 吕肖锋

    2014-01-01

    Objective To observe the effect of cilostazol combined with telmisartan on serum monocyte chemotactic pro-tein-1 (MCP-1) and soluble intercellular adhesion molecule-1 (sICAM-1) in early type 2 diabetic nephropathy. Methods A total of 60 patients with early type 2 diabetic nephropathy were randomly divided into two groups:thirty patients in group A were treated with cilostazol and telmisartan based on routine treatment, while thirty patients in group B were treated with telmisartan a-lone. The levels of 24-h urinary albumin, blood pressure, MCP-1, sICAM-1, alanine aminotransferase, creatinine and glycosy-lated hemoglobin in two groups were compared before treatment and 4 weeks after treatment. Results The levels of 24-h urinary albumin, MCP-1 and sICAM-1 were significantly decreased in both groups after treatment for four weeks, and the differences were significant (P<0. 05). After treatment, the levels of 24-h urinary albumin, MCP-1 and sICAM-1 in group A were obvious-ly lower than those in group B (P<0. 05). Conclusion Cilostazol combined with telmisartan can significantly decrease the uri-nary albumin level in the patients with early type 2 diabetes nephropathy, it can protect the kidney, and delay the progression of early diabetic nephropathy. It is relatively safe in clinical application.%目的:观察西洛他唑联合替米沙坦对早期2型糖尿病肾病( diabetic nephropathy, DN)血清单核细胞趋化蛋白1(MCP-1)和可溶性细胞间黏附分子1(sICAM-1)的影响。方法将我院收治的早期2型DN 60例随机分为西洛他唑联合替米沙坦组和替米沙坦组两组各30例,在常规治疗基础上西洛他唑联合替米沙坦组予西洛他唑和替米沙坦治疗,替米沙坦组仅予替米沙坦治疗,观察比较两组治疗前及治疗4周后24 h尿微量白蛋白、血压及血清MCP-1、sIcAM-1、丙氨酸转氨酶、肌酐、糖化血红蛋白水平。结果治疗4周后,两组24 h尿微量白蛋白及血清MCP-1、sIcAM-1均较

  1. Profile of circulating levels of IL-1Ra, CXCL10/IP-10, CCL4/MIP-1β and CCL2/MCP-1 in dengue fever and parvovirosis

    Directory of Open Access Journals (Sweden)

    Luzia Maria de-Oliveira-Pinto

    2012-02-01

    Full Text Available Dengue virus (DENV and parvovirus B19 (B19V infections are acute exanthematic febrile illnesses that are not easily differentiated on clinical grounds and affect the paediatric population. Patients with these acute exanthematic diseases were studied. Fever was more frequent in DENV than in B19V-infected patients. Arthritis/arthralgias with DENV infection were shown to be significantly more frequent in adults than in children. The circulating levels of interleukin (IL-1 receptor antagonist (Ra, CXCL10/inducible protein-10 (IP-10, CCL4/macrophage inflammatory protein-1 beta and CCL2/monocyte chemotactic protein-1 (MCP-1 were determined by multiplex immunoassay in serum samples obtained from B19V (37 and DENV-infected (36 patients and from healthy individuals (7. Forward stepwise logistic regression analysis revealed that circulating CXCL10/IP-10 tends to be associated with DENV infection and that IL-1Ra was significantly associated with DENV infection. Similar analysis showed that circulating CCL2/MCP-1 tends to be associated with B19V infection. In dengue fever, increased circulating IL-1Ra may exert antipyretic actions in an effort to counteract the already increased concentrations of IL-1β, while CXCL10/IP-10 was confirmed as a strong pro-inflammatory marker. Recruitment of monocytes/macrophages and upregulation of the humoral immune response by CCL2/MCP-1 by B19V may be involved in the persistence of the infection. Children with B19V or DENV infections had levels of these cytokines similar to those of adult patients.

  2. Profile of circulating levels of IL-1Ra, CXCL10/IP-10, CCL4/MIP-1β and CCL2/MCP-1 in dengue fever and parvovirosis.

    Science.gov (United States)

    de-Oliveira-Pinto, Luzia Maria; Gandini, Mariana; Freitas, Laís Picinini; Siqueira, Marilda Mendonça; Marinho, Cíntia Ferreira; Setúbal, Sérgio; Kubelka, Claire Fernandes; Cruz, Oswaldo Gonçalves; Oliveira, Solange Artimos de

    2012-02-01

    Dengue virus (DENV) and parvovirus B19 (B19V) infections are acute exanthematic febrile illnesses that are not easily differentiated on clinical grounds and affect the paediatric population. Patients with these acute exanthematic diseases were studied. Fever was more frequent in DENV than in B19V-infected patients. Arthritis/arthralgias with DENV infection were shown to be significantly more frequent in adults than in children. The circulating levels of interleukin (IL)-1 receptor antagonist (Ra), CXCL10/inducible protein-10 (IP-10), CCL4/macrophage inflammatory protein-1 beta and CCL2/monocyte chemotactic protein-1 (MCP-1) were determined by multiplex immunoassay in serum samples obtained from B19V (37) and DENV-infected (36) patients and from healthy individuals (7). Forward stepwise logistic regression analysis revealed that circulating CXCL10/IP-10 tends to be associated with DENV infection and that IL-1Ra was significantly associated with DENV infection. Similar analysis showed that circulating CCL2/MCP-1 tends to be associated with B19V infection. In dengue fever, increased circulating IL-1Ra may exert antipyretic actions in an effort to counteract the already increased concentrations of IL-1β, while CXCL10/IP-10 was confirmed as a strong pro-inflammatory marker. Recruitment of monocytes/macrophages and upregulation of the humoral immune response by CCL2/MCP-1 by B19V may be involved in the persistence of the infection. Children with B19V or DENV infections had levels of these cytokines similar to those of adult patients.

  3. Relationships between serum MCP-1 and subclinical kidney disease: African American-Diabetes Heart Study

    Directory of Open Access Journals (Sweden)

    Murea Mariana

    2012-11-01

    Full Text Available Abstract Background Monocyte chemoattractant protein-1 (MCP-1 plays important roles in kidney disease susceptibility and atherogenesis in experimental models. Relationships between serum MCP-1 concentration and early nephropathy and subclinical cardiovascular disease (CVD were assessed in African Americans (AAs with type 2 diabetes (T2D. Methods Serum MCP-1 concentration, urine albumin:creatinine ratio (ACR, estimated glomerular filtration rate (eGFR, and atherosclerotic calcified plaque (CP in the coronary and carotid arteries and infrarenal aorta were measured in 479 unrelated AAs with T2D. Generalized linear models were fitted to test for associations between MCP-1 and urine ACR, eGFR, and CP. Results Participants were 57% female, with mean ± SD (median age 55.6±9.5 (55.0 years, diabetes duration 10.3±8.2 (8.0 years, urine ACR 149.7±566.7 (14.0 mg/g, CKD-EPI eGFR 92.4±23.3 (92.0 ml/min/1.73m2, MCP-1 262.9±239.1 (224.4 pg/ml, coronary artery CP 280.1±633.8 (13.5, carotid artery CP 47.1±132.9 (0, and aorta CP 1616.0±2864.0 (319.0. Adjusting for age, sex, smoking, HbA1c, BMI, and LDL, serum MCP-1 was positively associated with albuminuria (parameter estimate 0.0021, P=0.04 and negatively associated with eGFR (parameter estimate −0.0003, P=0.001. MCP-1 remained associated with eGFR after adjustment for urine ACR. MCP-1 levels did not correlate with the extent of CP in any vascular bed, HbA1c or diabetes duration, but were positively associated with BMI. No interaction between BMI and MCP-1 was detected on nephropathy outcomes. Conclusions Serum MCP-1 levels are associated with eGFR and albuminuria in AAs with T2D. MCP-1 was not associated with subclinical CVD in this population. Inflammation appears to play important roles in development and/or progression of kidney disease in AAs.

  4. Effect of pharmacological intervention on MIP-1α, MIP-1β and MCP-1 expression in patients with psoriasis vulgaris

    Institute of Scientific and Technical Information of China (English)

    Yong-Jiang Dai; Yu-Yang Li; Hui-Ming Zeng; Xiong-An Liang; Zhi-Jie Xie; Zhi-Ang Zheng; Qin-Hui Pan; Yi-Xiong Xing

    2014-01-01

    Objective:To detect the expression level of macrophage inflammatory protein-1(MIP-1)α, MIP-1β and monocyte chemoattractant protein-1(MCP-1) in with psoriasis vulgaris and explore the role in the pathogenesis of psoriasis vulgaris.Methods:The level ofMIP-1α,MIP-1β andMCP-1 in peripheral blood from50 patients with psoriasis vulgaris and50 normal controls were measured by enzyme linked immunosorbent assay.The correlation with psoriasis area and severity index(PASI) was analyzed.The level ofMIP-1α,MIP-1β andMCP-1 was compared between psoriasis vulgaris patients at active stage and resting stage.And the change inMIP-1α, MIP-1β andMCP-1 before and after therapy was also observed.Results:The content ofMIP-1α, MIP-1β andMCP-1 in patients with psoriasis vulgaris was(1342.78±210.30),(175.28±28.18) and (266.86±32.75) ng/L, respectively, significantly higher than those in control group(P<0.05).The expression level ofMIP-1α,MIP-1β andMCP-1 in peripheral blood of patients with psoriasis vulgaris was positively correlated withPASI(P<0.01).After acitretin therapy, expression level ofMIP-1α,MIP-1β andMCP-1 in peripheral blood of patients with psoriasis vulgaris was significantly decreased.Conclusions:Chemokine factorMIP-1α,MIP-1β andMCP-1 may be involved in the pathogenesis of psoriasis vulgaris.

  5. Correlation of urinary monocyte chemo-attractant protein-1 with other parameters of renal injury in type-II diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Ibrahim Salwa

    2008-01-01

    Full Text Available Diabetic nephropathy (DN is the leading cause of end-stage renal disease in the western world. Increased number of interstitial macrophages has been observed in biopsies from patients with DN. Monocyte chemo-attractant protein-1 (MCP-1 is the strongest known chemo-tactic factor for monocytes and is upregulated in DN. We examined urinary levels of MCP-1 in patients with type-2 diabetes mellitus (DM to assess its possible correlation with other para-meters of renal injury. The urinary MCP-1 level was assessed in 75 patients with type-2 DM (25 patients each with no microalbuminuria, with macroalbuminuria and, with renal impairment and compared them with matched healthy control subjects. The HbA1c and estimated glomerular fil-tration rate (eGFR derived from the abbreviated Modification of Diet in Renal Disease (MDRD equation were examined in the study groups in relation to the urinary MCP-1. The urinary MCP-1 level was significantly higher in patients with micro and macroalbuminuria (167.41 ± 50.23 and 630.87 ± 318.10 ng/gm creatinine respectively as compared with normoalbuminuric patients and healthy controls (63.85 ± 21.15 and 61.50 ± 24.81 ng/gm creatinine, p< 0.001. MCP-1 correlated positively with urine albumin/creatinine ratio (ACR (r= 0.75, p< 0.001, HbA1c (r= 0.55, p< 0.001 and inversely with eGFR (r=-0.60, p< 0.001. Our findings suggest that hyperglycemia is associated with increased urinary levels of MCP-1 that is closely linked to renal damage as reflected by proteinuria and eGFR levels. Collectively, these findings suggest that MCP-1 is in-volved in the pathogenesis of diabetic nephropathy through its various stages.

  6. MCP-1-Induced Histamine Release from Mast Cells Is Associated with Development of Interstitial Cystitis/Bladder Pain Syndrome in Rat Models

    Directory of Open Access Journals (Sweden)

    Jianwei Lv

    2012-01-01

    Full Text Available Objective. Interstitial cystitis/bladder pain syndrome (IC/BPS is characterized by overexpression of monocyte chemoattractant protein-1 (MCP-1 in bladder tissues and induction of mast cell (MC degranulation. This study was undertaken to explore the mechanism of action of MCP-1 in the development of IC/BPS. Methods. A rat model of IC/BPS was developed by perfusing bladders of nine SPF- grade female Sprague-Dawley rats with protamine sulfate and lipopolysaccharide (PS+LPS. MCP-1 and histamine levels in bladder tissue and urine were detected by immunohistochemistry and ELISA. MC degranulation was measured by immunofluorescence techniques and chemokine (C-C motif receptor 2 (CCR2 was assayed by flow cytometry. Results. Increased MCP-1 expression in bladder tissue and elevated MCP-1 and histamine levels were observed in the urine of LS+LPS-treated rats. This was accompanied by the expression of CCR2 on MC surfaces, suggesting MCP-1 may induce MC degranulation through CCR2. Exposure to LPS stimulated MCP-1 expression in bladder epithelial cells, and exposure to MCP-1 induced histamine release from MCs. Conclusions. MCP-1 upregulation in IC/BPS is one of possible contributing factors inducing histamine release from MCs. CCR2 is involved in the process of mast cell degranulation in bladder tissues. These changes may contribute to the development of symptoms of IC/BPS.

  7. iPLA2β: front and center in human monocyte chemotaxis to MCP-1

    OpenAIRE

    Mishra, Ravi S.; Carnevale, Kevin A.; Cathcart, Martha K.

    2008-01-01

    Monocyte chemoattractant protein-1 (MCP-1) directs migration of blood monocytes to inflamed tissues. Despite the central role of chemotaxis in immune responses, the regulation of chemotaxis by signal transduction pathways and their in vivo significance remain to be thoroughly deciphered. In this study, we examined the intracellular location and functions of two recently identified regulators of chemotaxis, Ca2+-independent phospholipase (iPLA2β) and cytosolic phospholipase (cPLA2α), and subst...

  8. SP600125对1型糖尿病小鼠颈动脉内皮功能及单核细胞趋化蛋白1表达的影响%The Effect of SP600125 on Endothelial Function and Monocyte Chemotactic Protein-1 Expression in Carotid Artery in Type 1 Diabetic Mice

    Institute of Scientific and Technical Information of China (English)

    王启章; 陈茂刚; 李达文; 刘朝来; 徐格林; 刘新峰

    2011-01-01

    Aim The incidence of stroke in diabetes is increasing seriously, which is associated with endothelial dysfunction and increased inflammation in carotid artery.Our study is to investigate the effect of c-Jun arnino-terminal ki-nase (JNK) specific inhibitor SP600125 on carotid endothelial function and monocyte chemotactic protein-1 (MCP-1) expression in type 1 diabetes. Methods Animals were divided into five groups in this study. The 1st group was C57BL/6 wild type male mice; the 2nd group was INS2AKUTI male mice, intraperitoneal injection with 0. 9% normal saline (NS) each day for 8 weeks; the 3rd, 4th, 5th group were INS2AKITA male mice, intraperitoneal injection with SP600125 10 mg/kg, 20 mg/kg, 30 mg/kg respectively each day for consecutive 8 weeks. Then the mice were killed and sreum my-eloperoxidase (MPO) , malondialdehyde (MDA) , nitric oxide (NO) , total nitric oxide synthase (TNOS) were measured. HE staining was performed in carotid artery and immunohistochemistry was performed to investigate MCP-1 protein expression in endothelial cells of carotid artery. P-JNK, JNK, MCP-1 protein expression in carotid artery was measured by Western blot, signal transducer and activator of transcription-1 (STAT-1) DNA binding activity was assayed by electro-phoretic mobility shift assay (EMSA). Results Compared with wild type mice, serum MPO and MDA expression increased prominently (P <0. 05) , whereas TNOS, NO decreased and p-JNK/JNK, MCP-1 expression increased significantly in INS2AKITA mice (P<0.05); STAT-1 DNA binding activity increased prominently in type 1 diabetic group compared with that in control group (P <0. 05). Compared with type 1 diabetic mice, after treatment with SP600125, MPO decreased and NO, TNOS increased and p-JNK/JNK, endothelial MCP-1 expression decreased (P<0. 05). The effects of SP600125 on MPO, NO, TNOS, MCP-1 were increased accordingly as the dose of SP600125 increased. As the dose of SP600125 increased, MCP-1 protein expression decreased 21. 82

  9. MCP-1 Upregulates Amylin Expression in Murine Pancreatic β Cells through ERK/JNK-AP1 and NF-κB Related Signaling Pathways Independent of CCR2

    Science.gov (United States)

    Cai, Kun; Qi, Dongfei; Hou, Xinwei; Wang, Oumei; Chen, Juan; Deng, Bo; Qian, Lihua; Liu, Xiaolong; Le, Yingying

    2011-01-01

    Background Amylin is the most abundant component of islet amyloid implicated in the development of type 2 diabetes. Plasma amylin levels are elevated in individuals with obesity and insulin resistance. Monocyte chemoattractant protein-1 (MCP-1, CCL2) is involved in insulin resistance of obesity and type 2 diabetes. We investigated the effect of MCP-1 on amylin expression and the underlying mechanisms with murine pancreatic β-cell line MIN6 and pancreatic islets. Methodology/Principal Findings We found that MCP-1 induced amylin expression at transcriptional level and increased proamylin and intermediate forms of amylin at protein level in MIN6 cells and islets. However, MCP-1 had no effect on the expressions of proinsulin 1 and 2, as well as prohormone convertase (PC) 1/3 and PC2, suggesting that MCP-1 specifically induces amylin expression in β-cells. Mechanistic studies showed that although there is no detectable CCR2 mRNA in MIN6 cells and islets, pretreatment of MIN6 cells with pertussis toxin inhibited MCP-1 induced amylin expression, suggesting that alternative Gi-coupled receptor(s) mediates the inductive effect of MCP-1. MCP-1 rapidly induced ERK1/2 and JNK phosphorylation. Inhibitors for MEK1/2 (PD98059), JNK (SP600125) or AP1 (curcumin) significantly inhibited MCP-1-induced amylin mRNA expression. MCP-1 failed to induce amylin expression in pancreatic islets isolated from Fos knockout mice. EMSA showed that JNK and ERK1/2 were involved in MCP-1-induced AP1 activation. These results suggest that MCP-1 induces murine amylin expression through AP1 activation mediated by ERK1/2 or JNK. Further studies showed that treatment of MIN6 cells with NF-κB inhibitor or overexpression of IκBα dominant-negative construct in MIN6 cells significantly inhibited MCP-1-induced amylin expression, suggesting that NF-κB related signaling also participates in MCP-1-induced murine amylin expression. Conclusions/Significance MCP-1 induces amylin expression through ERK1/2/JNK

  10. MCP-1 upregulates amylin expression in murine pancreatic β cells through ERK/JNK-AP1 and NF-κB related signaling pathways independent of CCR2.

    Directory of Open Access Journals (Sweden)

    Kun Cai

    Full Text Available BACKGROUND: Amylin is the most abundant component of islet amyloid implicated in the development of type 2 diabetes. Plasma amylin levels are elevated in individuals with obesity and insulin resistance. Monocyte chemoattractant protein-1 (MCP-1, CCL2 is involved in insulin resistance of obesity and type 2 diabetes. We investigated the effect of MCP-1 on amylin expression and the underlying mechanisms with murine pancreatic β-cell line MIN6 and pancreatic islets. METHODOLOGY/PRINCIPAL FINDINGS: We found that MCP-1 induced amylin expression at transcriptional level and increased proamylin and intermediate forms of amylin at protein level in MIN6 cells and islets. However, MCP-1 had no effect on the expressions of proinsulin 1 and 2, as well as prohormone convertase (PC 1/3 and PC2, suggesting that MCP-1 specifically induces amylin expression in β-cells. Mechanistic studies showed that although there is no detectable CCR2 mRNA in MIN6 cells and islets, pretreatment of MIN6 cells with pertussis toxin inhibited MCP-1 induced amylin expression, suggesting that alternative Gi-coupled receptor(s mediates the inductive effect of MCP-1. MCP-1 rapidly induced ERK1/2 and JNK phosphorylation. Inhibitors for MEK1/2 (PD98059, JNK (SP600125 or AP1 (curcumin significantly inhibited MCP-1-induced amylin mRNA expression. MCP-1 failed to induce amylin expression in pancreatic islets isolated from Fos knockout mice. EMSA showed that JNK and ERK1/2 were involved in MCP-1-induced AP1 activation. These results suggest that MCP-1 induces murine amylin expression through AP1 activation mediated by ERK1/2 or JNK. Further studies showed that treatment of MIN6 cells with NF-κB inhibitor or overexpression of IκBα dominant-negative construct in MIN6 cells significantly inhibited MCP-1-induced amylin expression, suggesting that NF-κB related signaling also participates in MCP-1-induced murine amylin expression. CONCLUSIONS/SIGNIFICANCE: MCP-1 induces amylin expression

  11. MONOCYTE CHEMOTACTIC PROTEIN AND RESPONSE TO PEGYLATED INTERFERON-ALPHA-2A TREATMENT IN PATIENTS WITH CHRONIC HEPATITIS C (CHC) GENOTYPE 4.

    Science.gov (United States)

    Mohamed, Amal A; Sayed, Ola; Ali, Omnia E; Sayed, Ghadir A; Moustfa, Zainab; Elagawy, Waleed Ahmed

    2016-04-01

    The prevalence of hepatitis C virus (HCV) infection varies across the world, with the highest number of infections reported in Egypt. Monocyte chemotactic protein-1 (MCP-1) is a potent chemokine, and its hepatic expression is up-regulated during chronic HCV infection. Fifty naive patients with chronic hepatitis C in National Hepatology & Tropical Medicine Research Institute and 20 healthy volunteers as controls were enrolled in a prospective study designed with strict inclusion criteria to nullify the effect of confounding variables and further minimize selection bias. Fifty naive patients were treated with PEG-IFN-a2b, at a dose of 1801 g/kg subcutaneously every week plus ribavirin at a dose of 1000- 1200 mg/day, according to the patient's body weight, for 48 weeks. Quantification of HCV-RNA by real-time PCR and MCP-1 by ELISA were performed for every patient and controls. There was a sta- tistically significant difference between patients and control group as regards the quantity of MCP-1 (P < 0.05) (Mann-Whitney test) (P = 0.004). There was a significant difference between responders and nonresponses regarding MCP-1 (P < 0.05), responders showed a higher percentage of cases with initial MCP-1 < 306 (P < 0.05). We conclude the importance of the detection of MCP-1 expression at the start of therapy as a factor for assessing the likelihood of HCV genotype 4 patients to achieving a sustained virological response to treatment with IFN-a2 in combination with ribavirin. PMID:27363047

  12. CCL2/MCP-1 modulation of microglial activation and proliferation

    Directory of Open Access Journals (Sweden)

    Garcia-Bueno Borja

    2011-07-01

    Full Text Available Abstract Background Monocyte chemoattractant protein (CCL2/MCP-1 is a chemokine that attracts cells involved in the immune/inflammatory response. As microglia are one of the main cell types sustaining inflammation in brain, we proposed here to analyze the direct effects of MCP-1 on cultured primary microglia. Methods Primary microglia and neuronal cultures were obtained from neonatal and embryonic Wistar rats, respectively. Microglia were incubated with different concentrations of recombinant MCP-1 and LPS. Cell proliferation was quantified by measuring incorporation of bromodeoxyuridine (BrdU. Nitrite accumulation was measured using the Griess assay. The expression and synthesis of different proteins was measured by RT-PCR and ELISA. Cell death was quantified by measuring release of LDH into the culture medium. Results MCP-1 treatment (50 ng/ml, 24 h did not induce morphological changes in microglial cultures. Protein and mRNA levels of different cytokines were measured, showing that MCP-1 was not able to induce proinflammatory cytokines (IL-1β, IL6, MIP-1α, either by itself or in combination with LPS. A similar lack of effect was observed when measuring inducible nitric oxide synthase (NOS2 expression or accumulation of nitrites in the culture media as a different indicator of microglial activation. MCP-1 was also unable to alter the expression of different trophic factors that were reduced by LPS treatment. In order to explore the possible release of other products by microglia and their potential neurotoxicity, neurons were co-cultured with microglia: no death of neurons could be detected when treated with MCP-1. However, the presence of MCP-1 induced proliferation of microglia, an effect opposite to that observed with LPS. Conclusion These data indicate that, while causing migration and proliferation of microglia, MCP-1 does not appear to directly activate an inflammatory response in this cell type, and therefore, other factors may be

  13. CPG寡核苷酸对卵清蛋白致敏幼鼠血清中Th1/Th2细胞因子及肥大细胞趋化蛋白1的影响%Effect of CPG oligodeoxynucleotides on Th1/Th2 and mast cell chemotactic protein1 in serum with OVA induced food allergy in young mice

    Institute of Scientific and Technical Information of China (English)

    王本贞; 郑成中

    2015-01-01

    分;眼球取血,检测血清中OVA-IgE、肥大细胞趋化蛋白1(mast cell chemotactic protein 1,mMCP-1)及Th1/Th2相关细胞因子IFN-γ、IL-4的水平;空肠组织行病理学检测。结果除对照组外,致敏组小鼠均出现不同程度过敏症状,空肠表现为Ⅰ型变态反应病理特点,Th2细胞因子、OVA-IgE、mMCP-1水平升高,20μg、50μg致敏组Th1水平降低,50μg致敏组指标改变最显著;与致敏组相比,干预组小鼠过敏症状及病理改变明显减轻,Th2细胞因子、IgE及mMCP-1水平降低,Th1水平升高。结论用50μg OVA建立的BALB/c幼鼠食物过敏模型致敏效果最好,CPG-ODN通过改善Th1/Th2失衡状态,抑制幼鼠食物过敏反应。mMCP-1在过敏性疾病的发生、发展中起重要作用,有望成为食物过敏临床检测指标之一。

  14. Visfatin promotes production of monocyte chemotactic protein-1 and interleukin-6 in human endothelial cells via insulin receptor%内脏脂肪素促进内皮细胞合成单核细胞趋化蛋白1和白介素6的实验研究

    Institute of Scientific and Technical Information of China (English)

    刘圣文; 乔树宾; 刘东青

    2009-01-01

    Objective Visfatin is a new novel proinflammatory adipoeytokine affecting insulin resistance by binding to insulin receptor.To investigate whether visfatin stimulates monoeyte chemotaetic protein-1 (MCP-1) and interleukin-6 (IL-6) production in human umbilical vein endothelial cells (HUVEC) and mediates insulin receptor (IR) is involved in are not known.Methods Cultured HUVEC was treated with different doses and durations of visfatin.Furthermore,HUVEC was pretreated with hydroxy2-naphthalenylmethylphosphonic acid trisaeetoxymethyl ester (HNMPA-(AM)3),a specific inhibitor of IR followed by visfatin (100 ng/ml) treatment.Enzyme-linked immunosorbent assay (ELISA) were used to measure MCP-1 and IL-6 production in HUVEC.Real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) was used for determining MCP-1 and IL-6 mRNA expression.Results Visfatin significantly dose- and time-dependently up-regulated protein production of MCP-1 and IL-6 in HUVEC.We therefore found visfatin-induced MCP-1 and IL-6 production and gene expression in HUVEC were inhibited by HNMPA-(AM)3.Condusion Visfatin induces endothelial MCP-1 and IL-6 production in HUVEC in a dose and time-dependently manner.This action appears to be mediated via insulin receptor pathway.%目的 探讨内脏脂肪素是否能调节内皮细胞单核细胞趋化蛋白1(MCP-1)和白介素6(IL-6)生成以及胰岛素受体(IR)的介导作用.方法 不同剂量和不同干预时间的内脏脂肪素刺激3~5代脐静脉内皮细胞(HUVEC);然后在内脏脂肪素(100 ng/m1)刺激基础上加入IR酪氨酸激酶抑制剂预处理HUVEC,24 h后测定MCP-1和IL-6蛋白和基因表达.酶联免疫吸附法和实时定量聚合酶链反应检测MCP-1和IL-6蛋白和mRNA表达.结果 内脏脂肪素剂量和时间依赖性促进HUVEC合成MCP-1[剂量效应:对照组:(62±10) pg/ml、100 ng/ml:(273±65) pg/ml、500 ng/ml:(1630±103) pg/ml;时间效应:对照组:(37±27) pg/ml、12 h:(184±56) pg/ml、48 h

  15. Detection and clinical significance of MCP-1 in gingival crevicular fluid from patients with chronic periodontitis%慢性牙周炎患者龈沟液中MCP-1的检测及临床意义

    Institute of Scientific and Technical Information of China (English)

    张遵; 孙青; 王晓丽

    2011-01-01

    目的:检测慢性牙周炎患者龈沟液中单核细胞趋化蛋白-1(MCP-1)的浓度,并探讨其与牙周临床指标及碱性磷酸酶分泌的关系.方法:采用常规滤纸条法收集慢性牙周炎患者基础治疗前(T1)、基础治疗后(T2)及正常对照组(C)各位点的龈沟液样本,用ELISA法检测各样本中MCP-1及碱性磷酸酶的浓度.采用SPSS11.0软件包对数据进行t检验和直线相关分析.结果:3组受检者中,慢性牙周炎患者龈沟液中MCP-1平均浓度显著高于正常对照组(P<0.01),基础牙周治疗可使牙周炎患者龈沟液中MCP-1含量显著下降(P<0.01),治疗前后MCP-1的浓度变化与菌斑指数、探诊深度、牙龈指数、临床附着丧失以及碱性磷酸酶的分泌均呈正相关.结论:MCP-1作为一个重要的炎性趋化因子参与了慢性牙周炎的发生、发展过程,龈沟液MCP-1可作为牙周病防治及疗效评估的潜在靶分子.%PURPOSE: To evaluate the concentration of monocyte chemoattractant protein-1 (MCP-1) in the gingival crevicular fluid from patients with chronic periodontitis and its correlation with clinic periodontal parameters as well as alkaline phosphates secretions.METHODS: Gingival crevicular fluid (GCF) was collected with standardized filter strips from healthy control sites as well as periodontitis sites from chronic periodontitis patients before and after initial therapy,and the levels of MCP-1 and alkaline phosphatase were detected by ELISA.The data was analyzed with SPSS 11.0 software package.RESULTS: Concentration of MCP-1 in GCF was significantly higher in chronic periodontitis patients,and decreased significantly after initial therapy, the variation of MCP-1 correlated positively with clinical parameters like plaque index (PLI), probing depth (PD), gingival index (GI), clinic attachment lost (CAL) as well as alkaline phosphatase secretion.CONCLUSIONS: As an inflammatory chemotatic factor, MCP-1 in GCF may play an important role in occurrence

  16. Spiegelmer Inhibition of MCP-1/CCR2--Potential as an Adjunct Immunosuppressive Therapy in Transplantation.

    Science.gov (United States)

    Kalnins, A; Thomas, M N; Andrassy, M; Müller, S; Wagner, A; Pratschke, S; Rentsch, M; Klussmann, S; Kauke, T; Angele, M K; Bazhin, A V; Fischereder, M; Werner, J; Guba, M; Andrassy, J

    2015-08-01

    The rejection process remains the key unsolved issue after transplantation of disparate tissue. The CC chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2) has been reported to be involved in the process of alloimmune interaction. Spiegelmers are l-oligonucleotides that can be designed to bind to pharmacologically relevant target molecules. Here, we tested a high-affinity Spiegelmer-based MCP-1 inhibitor (mNOX-E36) in an allogeneic heart transplant model. Fully vascularized allogeneic heterotopic heart transplantations from BALB/c to C57BL/6 mice were performed. Mice were either treated with the anti-MCP-1-Spiegelmer (mNOX-E36) in monotherapy or in combination with subtherapeutic doses of cyclosporine A (CsA) (10 mg/kgBW/day) for 10 days. Controls received equivalent doses of a non-functional Spiegelmer (revmNOX-E36). Graft survival of allogeneic heart transplants was slightly but significantly prolonged under mNOX-E36 monotherapy (median graft survival 10 day ± 0.7) compared to revmNOX-E36 (median graft survival 7 day ± 0.3; P = 0.001). A synergistic beneficial effect could be seen when mNOX-E36 was administered in combination with subtherapeutic doses of CsA (18 day ± 2.8 versus 7 day ± 0.3; P rejection processes in allogeneic transplantation especially when combined with subtherapeutic doses of CsA. Thus, mNOX-E36 may have potential as an adjunct immunomodulatory agent. PMID:25970072

  17. Aspergillus antigen induces robust Th2 cytokine production, inflammation, airway hyperreactivity and fibrosis in the absence of MCP-1 or CCR2

    Directory of Open Access Journals (Sweden)

    Charo Israel F

    2004-09-01

    Full Text Available Abstract Background Asthma is characterized by type 2 T-helper cell (Th2 inflammation, goblet cell hyperplasia, airway hyperreactivity, and airway fibrosis. Monocyte chemoattractant protein-1 (MCP-1 or CCL2 and its receptor, CCR2, have been shown to play important roles in the development of Th2 inflammation. CCR2-deficient mice have been found to have altered inflammatory and physiologic responses in some models of experimental allergic asthma, but the role of CCR2 in contributing to inflammation and airway hyperreactivity appears to vary considerably between models. Furthermore, MCP-1-deficient mice have not previously been studied in models of experimental allergic asthma. Methods To test whether MCP-1 and CCR2 are each required for the development of experimental allergic asthma, we applied an Aspergillus antigen-induced model of Th2 cytokine-driven allergic asthma associated with airway fibrosis to mice deficient in either MCP-1 or CCR2. Previous studies with live Aspergillus conidia instilled into the lung revealed that MCP-1 and CCR2 play a role in anti-fungal responses; in contrast, we used a non-viable Aspergillus antigen preparation known to induce a robust eosinophilic inflammatory response. Results We found that wild-type C57BL/6 mice developed eosinophilic airway inflammation, goblet cell hyperplasia, airway hyperreactivity, elevations in serum IgE, and airway fibrosis in response to airway challenge with Aspergillus antigen. Surprisingly, mice deficient in either MCP-1 or CCR2 had responses to Aspergillus antigen similar to those seen in wild-type mice, including production of Th2 cytokines. Conclusion We conclude that robust Th2-mediated lung pathology can occur even in the complete absence of MCP-1 or CCR2.

  18. Monocytes infiltrate the pancreas via the MCP-1/CCR2 pathway and differentiate into stellate cells.

    Directory of Open Access Journals (Sweden)

    Kazuko Ino

    Full Text Available Recent studies have shown that monocytes possess pluripotent plasticity. We previously reported that monocytes could differentiate into hepatic stellate cells. Although stellate cells are also present in the pancreas, their origin remains unclear. An accumulation of enhanced green fluorescent protein (EGFP(+CD45(- cells was observed in the pancreases and livers of chimeric mice, which were transplanted with a single hematopoietic stem cell isolated from EGFP-transgenic mice and treated with carbon tetrachloride (CCl4. Because the vast majority of EGFP(+CD45(- cells in the pancreas expressed stellate cell-associated antigens such as vimentin, desmin, glial fibrillary acidic protein, procollagen-I, and α-smooth muscle actin, they were characterized as pancreatic stellate cells (PaSCs. EGFP(+ PaSCs were also observed in CCl4-treated mice adoptively transferred with monocytes but not with other cell lineages isolated from EGFP-transgenic mice. The expression of monocyte chemoattractant protein-1 (MCP-1 and angiotensin II (Ang II increased in the pancreas of CCl4-treated mice and their respective receptors, C-C chemokine receptor 2 (CCR2 and Ang II type 1 receptor (AT1R, were expressed on Ly6C(high monocytes isolated from EGFP-transgenic mice. We examined the effect of an AT1R antagonist, irbesartan, which is also a CCR2 antagonist, on the migration of monocytes into the pancreas. Monocytes migrated toward MCP-1 but not Ang II in vitro. Irbesartan inhibited not only their in vitro chemotaxis but also in vivo migration of adoptively transferred monocytes from peripheral blood into the pancreas. Irbesartan treatment significantly reduced the numbers of EGFP(+F4/80(+CCR2(+ monocytic cells and EGFP(+ PaSCs in the pancreas of CCl4-treated chimeric mice receiving EGFP(+ bone marrow cells. A specific CCR2 antagonist RS504393 inhibited the occurrence of EGFP(+ PaSCs in injured mice. We propose that CCR2(+ monocytes migrate into the pancreas possibly via the

  19. A MCP1 fusokine with CCR2-specific tumoricidal activity

    Directory of Open Access Journals (Sweden)

    Yuan Liangping

    2011-09-01

    Full Text Available Abstract Background The CCL2 chemokine is involved in promoting cancer angiogenesis, proliferation and metastasis by malignancies that express CCR2 receptor. Thus the CCL2/CCR2 axis is an attractive molecular target for anticancer drug development. Methods We have generated a novel fusion protein using GMCSF and an N-terminal truncated version of MCP1/CCL2 (6-76 [hereafter GMME1] and investigated its utility as a CCR2-specific tumoricidal agent. Results We found that distinct to full length CCL2 or its N-truncated derivative (CCL2 5-76, GMME1 bound to CCR2 on mouse lymphoma EG7, human multiple myeloma cell line U266, or murine and human medulloblastoma cell lines, and led to their death by apoptosis. We demonstrated that GMME1 specifically blocked CCR2-associated STAT3 phosphorylation and up-regulated pro-apoptotic BAX. Furthermore, GMME1 significantly inhibited EG7 tumor growth in C57BL/6 mice, and induced apoptosis of primary myeloma cells from patients. Conclusion Our data demonstrate that GMME1 is a fusokine with a potent, CCR2 receptor-mediated pro-apoptotic effect on tumor cells and could be exploited as a novel biological therapy for CCR2+ malignancies including lymphoid and central nervous system malignancies.

  20. "A system for the intracellular generation of triple helix-forming oligonucleotides (TFOs) and the sequence-specific inhibition of human MCP-1 gene expression"

    OpenAIRE

    Kautz, Kordula

    2006-01-01

    Chemokines play a key role in the cellular infiltration of inflamed tissue. They are released by a wide variety of cell types during the initial phase of host response to injury, allergens, antigens, or invading microorganisms, and selectively attract leukocytes to inflammatory foci, inducing both migration and activation. Monocyte chemoattractant protein-1 (MCP-1), a member of the CC chemokine superfamily, functions in attracting monocytes, T lymphocytes, and basophils to sites of inflammati...

  1. The Effect of Post-Resistance Exercise Amino Acids on Plasma MCP-1 and CCR2 Expression

    Directory of Open Access Journals (Sweden)

    Adam J. Wells

    2016-07-01

    Full Text Available The recruitment and infiltration of classical monocytes into damaged muscle is critical for optimal tissue remodeling. This study examined the effects of an amino acid supplement on classical monocyte recruitment following an acute bout of lower body resistance exercise. Ten resistance-trained men (24.7 ± 3.4 years; 90.1 ± 11.3 kg; 176.0 ± 4.9 cm ingested supplement (SUPP or placebo (PL immediately post-exercise in a randomized, cross-over design. Blood samples were obtained at baseline (BL, immediately (IP, 30-min (30P, 1-h (1H, 2-h (2H, and 5-h (5H post-exercise to assess plasma concentrations of monocyte chemoattractant protein 1 (MCP-1, myoglobin, cortisol and insulin concentrations; and expressions of C-C chemokine receptor-2 (CCR2, and macrophage-1 antigen (CD11b on classical monocytes. Magnitude-based inferences were used to provide inferences on the true effects of SUPP compared to PL. Changes in myoglobin, cortisol, and insulin concentrations were similar between treatments. Compared to PL, plasma MCP-1 was “very likely greater” (98.1% likelihood effect in SUPP at 2H. CCR2 expression was “likely greater” at IP (84.9% likelihood effect, “likely greater” at 1H (87.7% likelihood effect, “very likely greater” at 2H (97.0% likelihood effect, and “likely greater” at 5H (90.1% likelihood effect in SUPP, compared to PL. Ingestion of SUPP did not influence CD11b expression. Ingestion of an amino acid supplement immediately post-exercise appears to help maintain plasma MCP-1 concentrations and augment CCR2 expression in resistance trained men.

  2. sPLA2-IIA Augments Oxidized LDL-Induced MCP-1 Expression in Vitro Through Activation of Akt

    Directory of Open Access Journals (Sweden)

    Yongjun Guo

    2015-10-01

    Full Text Available Background/Aims: Group IIA secretory phospholipase A2 (sPLA2-IIA has an important role in atherosclerosis. In this study, we explored whether sPLA2-IIA overexpression could promote atherosclerosis in normal environment alone or with other inflammatory factors. Methods: Human aortic smooth muscle cells (HASMCs were transduced with Lv-GFP-sPLA2-IIA, a plasmid containing sPLA2-IIA coupled with green fluorescent protein (GFP. Cells were incubated in the presence or absence of oxidized low-density lipoprotein (LDL, sPLA2 inhibitor LY315920 or PI3K/Akt inhibitor LY294002. The mRNA expression and protein secretion of monocyte chemoattractant protein-1 (MCP-1 were assessed by quantitative real-time polymerase chain reaction (QRT-PCR and enzyme-linked immunosorbent assay (ELISA, respectively. Phosphorylation of Akt was examined by western blotting. Results: Lv-GFP-sPLA2-IIA-transduced HASMCs remained fluorescent during 72 h of the study period with infection ratio of around 80%. The mRNA expression and protein secretion of MCP-1was not altered in groups of HASMCs, Lv-GFP transduced and Lv-GFP-sPLA2-IIA-transduced HASMCs (p>0.05, but was significantly increased in the presence of oxidized LDL especially in Lv-GFP-sPLA2-IIA transduction group (ppConclusions: Overexpression of sPLA2-IIA does not alter MCP-1 level at baseline, but could enhance the atherogenic effect of oxidized LDL in HASMCs, at least partly due to activation of Akt. These findings may provide a strategy for treatment of inflammatory cardiovascular diseases.

  3. 六味地黄汤对单侧输尿管结扎大鼠肾间质MCP-1及TGF-β1表达的影响%Effect of Liuweidihuang Decoction on Expression of Tubuloninterstitial MCP - 1 and TGF - β1 in Unilateral Ureter Ligation Rats

    Institute of Scientific and Technical Information of China (English)

    彭亚军; 张继波; 何泽云; 李杨; 刘芳洁; 李颂婷; 崔晓燕

    2009-01-01

    Objective:To observe the effect of Liuweidihuang decoction(LD)on expression of monocyte chemotactic protein (MCP-1) and transforming growth factor(TGF-β1) in unilateral ureter obstraction(UUO) rats. Methods: Seventy- two male Sprague- Dawley rats were randomly divided into four groups: the model group, the sham- operation group, the Enalapril group and LD group. The kidneys of rats were harversted at 7,14 and 21 d after the operation, lmmunohistochemistry was used on the renal tissue for MCP- 1 and TGF-β1after7,14 and 21 day. Histological changes were also observed by HE and Masson staining. Results:Compared with those in the sham-operation group, the levels of MCP- 1 and TGF-β1expression was obviously higher than those in the other groups on day 7,14,and 21(P<0.05).The MCP- 1 and TGF-β1of in LD group was higher than that in Enalapril group on day 7,14,and 21(P<0.05). Conclusion: LD can decrease the expression of the UUO MCP- 1 and level and TGF-β1andreduce tubuloninterstitial injury,and LD can be an axillary drug for obstruct kidney disease.%目的:观察六味地黄汤对单侧输尿管梗阻(UUO)大鼠模型中单核趋化蛋白-1(MCP-1)及转化生长因子-β1(TGF-β1)表达的影响.方法:将72只雄性SD大鼠随机分为模型组、依那普利组、六味地黄汤组、假手术组,行UUO术后即预药物干预.于术后第7、14、21天分别处死各组大鼠.用HE和Masson染色法观察各组大鼠术后不同时间点肾脏病理改变,用免疫组化法检测肾小管间质MCP-1及TGF-β1表达.结果:与假手术组比较,其余3组各时间点MCP-1及TGF-β1表达均明显高于假手术组(P<0.05);六味地黄汤组的MCP-1和TGF-β1表达明显低于模型组各时间点(P<0.05),高于依那普利组(P<0.05).结论:六味地黄汤可下调MCP-1和TGF-β1的表达,减缓UUO大鼠肾小管间质损害,可作为梗阻性肾病辅助用药.

  4. Allelic frequency of the MCP-1 promoter -2518 polymorphism in the Turkish population and in Turkish patients with juvenile rheumatoid arthritis.

    Science.gov (United States)

    Ozyürek, A Ruhi; Gürses, Dolunay; Ulger, Zülal; Levent, Ertürk; Bakiler, A Rahmi; Berdeli, Afig

    2007-04-01

    Although genetic and environmental factors contribute to the pathogenesis of juvenile rheumathoid arthritis (JRA), the etiology and pathogenesis remain controversial. The objective of this study was to investigate genotypic and allelic frequencies of monocyte chemoattractant protein-1 (MCP-1) gene -2518 (G/A) polymorphism in the healthy Turkish population and patients with JRA. Genomic DNA was collected from 66 JRA patients and 150 healthy individuals. To evaluate the association of the -2518 (G/A) MCP-1 gene polymorphism with the outcome of JRA, we analyzed the types of JRA and the score on the childhood health assessment questionnaire (C-HAQ score). In the healthy Turkish population, the frequencies of A and G alleles were 71 and 29%, respectively. No significant difference was observed between the JRA patients and healthy subjects in the distribution allelic and genotypic frequencies of the -2518 (G/A) MCP-1 gene polymorphism (p>0.05). However, the AG genotype was found to be higher and the AA genotype was found to be lower in the patients with systemic type JRA compared to those with the other types of JRA (p=0.019). When the JRA patients were evaluated according to the C-HAQ score, we found that the -2518 (G/A) MCP-1 gene polymorphism did not relate the prognosis (p>0.05). AG genotype was found to be higher in the systemic type of JRA. The results indicate that MCP-1 gene polymorphism might slightly associate with patients with systemic JRA. Further studies are needed to elucidate the role of this polymorphism in the pathogenesis of JRA in various populations because this polymorphism has a functional significance and an ethnic difference.

  5. Correlation study on MCP-1, MMP-1 gene polymorphism and the incidence of tuberculosis in BCG-vaccinated individuals%卡介苗接种者MCP-1、MMP-1基因多态性与肺结核发病率的相关性研究

    Institute of Scientific and Technical Information of China (English)

    夏小学; 陈江; 张美禄; 沈志成; 余文菁; 卢火佺

    2013-01-01

    目的:探讨我国汉族人群单核细胞趋化蛋白-1(MCP-1)基因-2518位点、基质金属蛋白酶-1(MMP-1)基因-1607位点多态性与肺结核发病的相关性.方法:选择有卡介苗接种史的肺结核患者188例(TB组)与结核菌素皮试阳性的健康者194例(PPD+组).分析两组人群MCP-1-2518 A/G位点、MMP-1-1607 1G/2G位点基因型、等位基因频率及与肺结核发病的关系.结果:两组人群MCP-1-2518A/G位点、MMP-1-1607 1G/2G位点基因型、等位基因频率分布符合Hardy-Weinberg平衡定律.MCP-1-2518 G、MMP-1-1607 2G等位基因的频率分布与肺结核的发病有显著相关性(P<0.01),MCP-1-2518G/G、MMP-1-1607 2G/2G表型易患肺结核(P<0.05).结论:我国汉族人群MCP-1-2518 G/G表型、MMP-1-1607 2G/2G表型与肺结核的发生有显著相关性.%Objective:To investigate the correlation between monocyte chemoattractant protein-1 (MCP-1)gene-2518 loci,matrix metalloproteinase-1 (MMP-1) gene-1607 loci polymorphism and the incidence of tuberculosis in the Chinese Han population.Methods:One hundred and eighty-eight cases of tuberculosis patients (TB group) and 194 healthy volunteers with positive tuberculin skin test (PPD group) were selected as BCG-vaccinated individuals.The genotype and allele frequencies of MCP-1-2518 A/G locus,MMP-1-1607 1G/2G locus,and the relationship with the incidence of TB were analyzed.Results:The MCP-1-2518 A/G locus,MMP -1-1607 1G/2G locus,allele freauency distribution of the two groups conformed to Hardy-Weinberg equilibrium.The significant correlation was found MCP-1-2518 G,MMP-1-1607 2G allele frequency distribution and the incidence of TB (P <0.01),and MCP-1-2518 G/G,MMP-1-1607 2G/2G phenotype were susceptible to tuberculosis (P < 0.05).Conclusion:The MCP-1-2518 G/G,MMP-1-1607 2G/2G phenotype might be associated with susceptibility to tuberculosis in Chinese Han population.

  6. Research Progress on the Role of MCP-1/CCR2 Signaling Axis in the Development of Gastrointestinal Tumors%MCP-1/CCR2信号轴在消化系统肿瘤发生发展中的研究进展

    Institute of Scientific and Technical Information of China (English)

    刘天宇; 曹海龙; 王邦茂

    2016-01-01

    单核细胞趋化蛋白1(MCP-1)/CC 趋化因子受体2(CCR2)信号轴是指由趋化因子 MCP-1与其特异性受体 CCR2相互作用构成的一个与细胞间信息传递和细胞迁移有密切关系的耦联分子对,在肿瘤细胞以及肿瘤微环境中的多种细胞中表达,对肿瘤的发生发展起重要作用。在消化系统肿瘤发生发展过程中, MCP-1/CCR2信号轴的作用越来越受到国内外的关注,相关分子机制研究涉及肿瘤相关巨噬细胞的募集和极化,新生血管生成及异常免疫反应等,可为消化系统肿瘤防治提供新的思路。本文就近年来对 MCP-1/CCR2信号轴与消化系统肿瘤发生发展的研究进展进行综述。%Monocyte chemoattractant protein-1 (MCP-1) / CC chemokine receptor 2 (CCR2) signaling axis is defined as a coupled molecule that was made up by the interaction between chemokine MCP-1 and its specific receptor CCR2 and closely related to the intercellular information transmission and cell migration. MCP-1/CCR2 signal axis is expressed in tu-mor cells and a variety of cells in tumor microenvironment. It plays an important role in the development of tumor. Its role in the development of digestive system neoplasm received increasing attention from researchers in the world. The mechanisms involved the recruitment and polarization of tumor-associated macrophages, angiogenesis and abnormal immune response, etc. It would provide new ideas for the prevention and treatment of gastrointestinal tumors. The present article summarized the recent advances in the role of MCP-1/CCR2 signaling axis in the development of gastrointestinal tumors, and outlined the future prospect.

  7. MCP-1/CCR2 axis promotes the homing of human umbilical cord mesenchymal stem cells to lung cancer tissues%MCP-1/CCR2轴促进脐带间充质干细胞向肺癌组织归巢

    Institute of Scientific and Technical Information of China (English)

    宋新苗; 颜次慧; 吕梦果; 于文文; 张新伟; 任秀宝

    2016-01-01

    目的:探讨单核细胞趋化蛋白-l(monocyte chemoatractant protein-1,MCP-1)/趋化因子(C-C模体)受体2[chemokine(C-C motif) receptor 2,CCR2)轴在人脐带间充质干细胞(human umbilical cord mesenchymal stem cells,HUMSCs)向肺癌归巢中的作用.方法:采用组织块培养法从健康新生儿脐带组织中分离HUMSCs并鉴定,构建BALB/c裸鼠皮下移植瘤模型.体外应用Transwell趋化实验、体内应用IVIS Xenogen动物活体成像系统检测HUMSCs是否向肺癌归巢,ELISA法检测肺癌细胞A549培养上清中MCP-1分泌水平,转染shRNA敲低肺癌细胞内MCP-1的表达和用抑制剂RS504393抑制HUMSCs细胞表面的MCP-1受体CCR2后,体内外检测HUMSCs向肺癌归巢能力的改变.结果:成功分离得到HUMSCs并完成鉴定,成功建立BALB/c裸鼠皮下肺癌移植瘤模型.HUMSCs在体内外均能向肺癌归巢(P<0.01),肺癌细胞高表达MCP-1.成功构建稳定低表达MCP-1的肺癌A549细胞系,与对照组相比,shRNA1和shRNA2敲低组趋化HUMSCs的数目明显减少[(80.0±33.0)、(94.0±16.0)vs (167.0±41.0)个,均P<0.05],抑制HUMSCs细胞表面MCP-1受体CCR2后,体内外均显著抑制HUMSCs向肺癌的趋化能力(P<0.05).结论:MCP-1/CCR2轴促进HUMSCs向肺癌归巢.

  8. Regulation of MCP-1 gene transcription by Smads and HIV-1 Tat in human glial cells

    International Nuclear Information System (INIS)

    Expression of several cytokines involved in signal transduction such as TGFβ-1 and the inflammatory chemokines including MCP-1 is elevated during the course of AIDS progression. The enhancement of these cellular proteins in astrocytic cells is mediated, at least in part, by HIV-1 Tat protein. Here, we investigate the possible regulation of MCP-1 transcription by Tat and the Smad family of transcription factors whose activities are induced by the TGFβ-1 pathway. Results from transfection studies revealed that Smad-3 stimulates basal and Tat-mediated transcription of MCP-1 in human astrocytic cells. Smad-4, on the other hand, had no effect on the basal activity of the MCP-1 promoter, but showed the ability to decrease both Smad-3 and Tat-induced transcription of the MCP promoter. Results from protein-binding studies revealed the ability of both Smad-3 and Smad-4 to associate with the region of Tat spanning residues 1-40. Examination of the transcriptional activity of the various domains of Smad including MH1, at the N-terminus, and MH2, at the C-terminus of the protein indicated that neither MH1 or MH2 alone positively cooperate with Tat in modulating MCP-1 transcription. However, ectopic expression of MH1 and, more notably, MH2 severely suppressed transcriptional activation of MCP-1 by Tat in astrocytic cells. Binding studies revealed that similar to the full-length Smad protein, both MH1 and MH2 associate with Tat protein and that the residues between 1 and 40 of Tat are important for their interaction. These observations reveal a novel mechanism for Tat-mediated transcriptional activation via TGFβ signaling pathway and provide evidence for regulation of MCP-1 gene transcription by this signaling pathway in human astrocytic cells

  9. Effect of Dangguishaoyaosan on the blood lipids and the expression of inflammatory factors, such as IL-6, MCP-1, NF-κB and PPAR-γmRNA in the metaflammatory mice%当归芍药散对代谢性炎性反应小鼠血脂和血清炎性反应因子IL-6、MCP-1及 NF-κB、PPARγmRNA 表达的影响

    Institute of Scientific and Technical Information of China (English)

    贾丽超; 周明学; 张蕾; 刘卫红

    2014-01-01

    目的:研究当归芍药散对代谢性炎性反应小鼠血脂和血清炎性反应因子白细胞介素-6(interleukin-6,IL-6)、单核细胞趋化蛋白-1(monocyte chemotactic protein 1,MCP-1)以及核因子κB (nuclear factor kappa B,NF-κB)和活化的过氧化物酶体增生物激活受体γ(peroxisome proliferator-activated receptor gamma,PPARγ)mRNA 表达的影响。方法60只雄性 C57小鼠,采用数字表法将动物随机分为正常组、模型组、立普妥组、当归芍药散组(n =15)。采用高脂饮食联合脂多糖注射造成小鼠代谢性炎性反应模型。造模5周后,开始灌胃给药,每天2次,当归芍药散2.2 g/ kg,立普妥0.003 g/ kg。正常对照组和模型组灌服等体积蒸馏水。连续灌胃5周。处死后采血和取肝脏,检测各组小鼠血清胆固醇(total cholesterol,TC)、三酰甘油(triglyceride,TG)和低密度脂蛋白胆固醇(low density lipoprotein,LDL-C)浓度,并采用流式细胞术检测血清炎性反应因子 IL-6和 MCP-1浓度。反转录聚合酶链式反应(reverse transcription polymerase chain reaction,RT-PCR)法测定肝脏 NF-κB 和 PPARγmRNA 的表达。结果与模型组相比,当归芍药散组小鼠血清 TC 和 LDL-C 水平明显降低(P<0.01),肝脏组织中 NF-κB mRNA 的表达降低,差异有统计学意义(P<0.05),PPARγmRNA 的表达提高,差异有统计学意义(P<0.05)。结论当归芍药散可降低代谢性炎性反应小鼠血脂和血清炎性反应因子 IL-6和 MCP-1浓度,并可通过调控核转录因子 NF-κB 和 PPARγ受体,抑制小鼠体内代谢性炎性反应,从而可能对早期动脉粥样硬化起到干预作用。%Objective To study the effect of Dangguishaoyaosan on the blood lipids and the expression of inflammatory factors, such as IL-6, MCP-1, NF-κB and PPAR-γ mRNA in the metaflammatory mice. Methods Sixty male C57 mice were randomly divided into normal group, model group, the lipitor group and Dangguishaoyaosan group(n = 15). High

  10. 当归芍药散对代谢性炎性反应小鼠血脂和血清炎性反应因子IL-6、MCP-1及 NF-κB、PPARγmRNA 表达的影响%Effect of Dangguishaoyaosan on the blood lipids and the expression of inflammatory factors, such as IL-6, MCP-1, NF-κB and PPAR-γmRNA in the metaflammatory mice

    Institute of Scientific and Technical Information of China (English)

    贾丽超; 周明学; 张蕾; 刘卫红

    2014-01-01

    Objective To study the effect of Dangguishaoyaosan on the blood lipids and the expression of inflammatory factors, such as IL-6, MCP-1, NF-κB and PPAR-γ mRNA in the metaflammatory mice. Methods Sixty male C57 mice were randomly divided into normal group, model group, the lipitor group and Dangguishaoyaosan group(n = 15). High-fat diets joining lipopolysaccharide injection were used to build the metabolic inflammatory model in mice. Five weeks later, all groups in addition to the normal were given a gavage twice a day for five weeks,according to the dose conversed from the clinical equivalent dose. When the test was finished, we collect the blood and liver, test the serum cholesterol( TC), triglyceride( TG) and low density lipoprotein cholesterol( LDL-C) level, using flow cytometry to detect the serum level of IL-6 and MCP-1. Reverse transcription polymerase chain reaction(RT-PCR) was used to detect the expression of NF-κB and PPAR-γ mRNA in liver. Results Compared with the model group, the serum TC and LDL-C level of Dangguishaoyaosan group significantly decreased(P<0. 01), and the expression of NF-κB mRNA in liver tissue decreased significantly(P<0. 01), while the expression of PPAR-γmRNA significantly increased(P<0. 01). Conclusion Dangguishaoyaosan can reduce the blood lipid, IL-6 and MCP-1 level of metabolic inflammation mice, and can influence metabolic inflammation in mice, which might have an intervention effect on the early atherosclerosis through regulating nuclear transcription factor NF-κB and PPAR-γ receptors.%目的:研究当归芍药散对代谢性炎性反应小鼠血脂和血清炎性反应因子白细胞介素-6(interleukin-6,IL-6)、单核细胞趋化蛋白-1(monocyte chemotactic protein 1,MCP-1)以及核因子κB (nuclear factor kappa B,NF-κB)和活化的过氧化物酶体增生物激活受体γ(peroxisome proliferator-activated receptor gamma,PPARγ)mRNA 表达的影响。方法60只雄性 C57小鼠,采用数字表法将动物随机

  11. Effects of Roux-en-Y Gastric Bypass on Fasting and Postprandial Levels of the Inflammatory Markers YKL-40 and MCP-1 in Patients with Type 2 Diabetes and Glucose Tolerant Subjects

    Directory of Open Access Journals (Sweden)

    Stine Brinkløv Thomsen

    2013-01-01

    Full Text Available Background. The inflammatory markers YKL-40 and monocyte chemoattractant protein-1 (MCP-1 are elevated in morbidly obese patients and decline after weight loss. The objective of our study was to investigate the possible changes of YKL-40 and MCP-1, in both the fasting and the postprandial states, following Roux-en-Y gastric bypass (RYGB in subjects with type 2 diabetes (T2D and normal glucose tolerance (NGT. Methods. Ten obese patients with T2D and 10 subjects with NGT were examined in the fasting state and after a standard meal prior to and after (1 week, 3 months, and 1 year RYGB. Results. Fasting state MCP-1 levels decreased after RYGB in both groups (P values < 0.0001 whereas fasting YKL-40 levels were unchanged (P values ≥ 0.120. Postprandial MCP-1 levels showed a tendency towards a decrease on most study days; however, the changes were only significant at 1 week (P=0.001 and 1 yr (P<0.0001 in the T2D group and at 3 mo after RYGB in the NGT group (P=0.009. YKL-40 levels showed a slight, postprandial suppression on all study days in the T2D group (all P values ≤ 0.021. Conclusions. Fasting MCP-1 levels, but not YKL-40 levels, decrease after RYGB in subjects with T2D and NGT. Postprandial changes of inflammatory markers are discrete and inconsistent.

  12. LOX - 1介导ox - LDL诱导的血管内皮细胞MCP - 1的表达%Lectin- like oxidized low density lipoprotein receptor - 1 mediates expression of MCP - 1 induced by ox - LDL in cultured human vascular endothelial cells

    Institute of Scientific and Technical Information of China (English)

    朱惠莲; 唐志红; 夏敏; 马静; 凌文华

    2005-01-01

    目的:观察血凝素氧化低密度脂蛋白受体-1(LOX-1)对氧化LDL(ox-LDL)诱导的人脐静脉内皮细胞(human unbilical vein endothelial cells,HUVECs)表达单核细胞趋化蛋白(monocyte chemoattractant protein-1,MCP-1)基因及蛋白的影响.方法:用RT-PCR和Western blot的方法观察ox-LDL对培养的HUVECs表达LOX-1和MCP-1基因及蛋白的影响,然后用LOX-1的受体阻滞剂爱兰苔胶(carrageenan)和聚肌苷酸[polyinosinic acid,poly(Ⅰ)]与HUVECs预先作用后,再观察内皮细胞表达LOX-1和MCP-1基因和蛋白的变化.结果:用不同浓度的ox-LDL(0 mg/L、10 mg/L、20 mg/L、50 mg/L、100 mg/L)与HUVECs培养24h后,LOX-1和MCP-1的mRNA和蛋白的表达明显增加,呈浓度依赖性;用Carrageenan和polyinosinic acid与HUVECs预先作用2 h后,再加入50 mg/L的ox-LDL培养24 h,与未加Carrageenan和polyinosinic acid相比,HUVECsLOX-1和MCP-1的mRNA和蛋白的表达明显减少.结论:ox-LDL可以调节培养的HUVECsLOX-1和MCP-1基因和蛋白的表达,LOX-1作为ox-LDL的特异性受体,可能介导了ox-LDL诱导血管内皮细胞分泌MCP-1,从而在动脉粥样硬化的发生发展中起着重要的作用.

  13. The host response to the probiotic Escherichia coli strain Nissle 1917: Specific up-regulation of the proinflammatory chemokine MCP-1

    Directory of Open Access Journals (Sweden)

    Ukena Sya N

    2005-12-01

    Full Text Available Abstract Background The use of live microorganisms to influence positively the course of intestinal disorders such as infectious diarrhea or chronic inflammatory conditions has recently gained increasing interest as a therapeutic alternative. In vitro and in vivo investigations have demonstrated that probiotic-host eukaryotic cell interactions evoke a large number of responses potentially responsible for the effects of probiotics. The aim of this study was to improve our understanding of the E. coli Nissle 1917-host interaction by analyzing the gene expression pattern initiated by this probiotic in human intestinal epithelial cells. Methods Gene expression profiles of Caco-2 cells treated with E. coli Nissle 1917 were analyzed with microarrays. A second human intestinal cell line and also pieces of small intestine from BALB/c mice were used to confirm regulatory data of selected genes by real-time RT-PCR and cytometric bead array (CBA to detect secretion of corresponding proteins. Results Whole genome expression analysis revealed 126 genes specifically regulated after treatment of confluent Caco-2 cells with E. coli Nissle 1917. Among others, expression of genes encoding the proinflammatory molecules monocyte chemoattractant protein-1 ligand 2 (MCP-1, macrophage inflammatory protein-2 alpha (MIP-2α and macrophage inflammatory protein-2 beta (MIP-2β was increased up to 10 fold. Caco-2 cells cocultured with E. coli Nissle 1917 also secreted high amounts of MCP-1 protein. Elevated levels of MCP-1 and MIP-2α mRNA could be confirmed with Lovo cells. MCP-1 gene expression was also up-regulated in mouse intestinal tissue. Conclusion Thus, probiotic E. coli Nissle 1917 specifically upregulates expression of proinflammatory genes and proteins in human and mouse intestinal epithelial cells.

  14. PPAR agonist-induced reduction of Mcp1 in atherosclerotic plaques of obese, insulin-resistant mice depends on adiponectin-induced Irak3 expression.

    Directory of Open Access Journals (Sweden)

    Maarten Hulsmans

    Full Text Available Synthetic peroxisome proliferator-activated receptor (PPAR agonists are used to treat dyslipidemia and insulin resistance. In this study, we examined molecular mechanisms that explain differential effects of a PPARα agonist (fenofibrate and a PPARγ agonist (rosiglitazone on macrophages during obesity-induced atherogenesis. Twelve-week-old mice with combined leptin and LDL-receptor deficiency (DKO were treated with fenofibrate, rosiglitazone or placebo for 12 weeks. Only rosiglitazone improved adipocyte function, restored insulin sensitivity, and inhibited atherosclerosis by decreasing lipid-loaded macrophages. In addition, it increased interleukin-1 receptor-associated kinase-3 (Irak3 and decreased monocyte chemoattractant protein-1 (Mcp1 expressions, indicative of a switch from M1 to M2 macrophages. The differences between fenofibrate and rosiglitazone were independent of Pparγ expression. In bone marrow-derived macrophages (BMDM, we identified the rosiglitazone-associated increase in adiponectin as cause of the increase in Irak3. Interestingly, the deletion of Irak3 in BMDM (IRAK3(-/- BMDM resulted in activation of the canonical NFκB signaling pathway and increased Mcp1 protein secretion. Rosiglitazone could not decrease the elevated Mcp1 secretion in IRAK3(-/- BMDM directly and fenofibrate even increased the secretion, possibly due to increased mitochondrial reactive oxygen species production. Furthermore, aortic extracts of high-fat insulin-resistant LDL-receptor deficient mice, with lower adiponectin and Irak3 and higher Mcp1, showed accelerated atherosclerosis. In aggregate, our results emphasize an interaction between PPAR agonist-mediated increase in adiponectin and macrophage-associated Irak3 in the protection against atherosclerosis by PPAR agonists.

  15. PPAR Agonist-Induced Reduction of Mcp1 in Atherosclerotic Plaques of Obese, Insulin-Resistant Mice Depends on Adiponectin-Induced Irak3 Expression

    Science.gov (United States)

    Arnould, Thierry; Tsatsanis, Christos; Holvoet, Paul

    2013-01-01

    Synthetic peroxisome proliferator-activated receptor (PPAR) agonists are used to treat dyslipidemia and insulin resistance. In this study, we examined molecular mechanisms that explain differential effects of a PPARα agonist (fenofibrate) and a PPARγ agonist (rosiglitazone) on macrophages during obesity-induced atherogenesis. Twelve-week-old mice with combined leptin and LDL-receptor deficiency (DKO) were treated with fenofibrate, rosiglitazone or placebo for 12 weeks. Only rosiglitazone improved adipocyte function, restored insulin sensitivity, and inhibited atherosclerosis by decreasing lipid-loaded macrophages. In addition, it increased interleukin-1 receptor-associated kinase-3 (Irak3) and decreased monocyte chemoattractant protein-1 (Mcp1) expressions, indicative of a switch from M1 to M2 macrophages. The differences between fenofibrate and rosiglitazone were independent of Pparγ expression. In bone marrow-derived macrophages (BMDM), we identified the rosiglitazone-associated increase in adiponectin as cause of the increase in Irak3. Interestingly, the deletion of Irak3 in BMDM (IRAK3−/− BMDM) resulted in activation of the canonical NFκB signaling pathway and increased Mcp1 protein secretion. Rosiglitazone could not decrease the elevated Mcp1 secretion in IRAK3−/− BMDM directly and fenofibrate even increased the secretion, possibly due to increased mitochondrial reactive oxygen species production. Furthermore, aortic extracts of high-fat insulin-resistant LDL-receptor deficient mice, with lower adiponectin and Irak3 and higher Mcp1, showed accelerated atherosclerosis. In aggregate, our results emphasize an interaction between PPAR agonist-mediated increase in adiponectin and macrophage-associated Irak3 in the protection against atherosclerosis by PPAR agonists. PMID:23620818

  16. Association of MCP-1-2518A/G polymorphism with uveitis susceptibility: a Meta-analysis%MCP-1基因-2518A/G多态性与葡萄膜炎易感性的Meta分析

    Institute of Scientific and Technical Information of China (English)

    张小玲; 冀垒兵; 高晓唯; 肖云; 章玮; 张燕

    2015-01-01

    Background Monocyte chemoattractant protein-1 (MCP-1) polymorphisms are demonstrated to be significantly associated with the susceptibility to uveitis in recent years,while a consistent conclusion for the association of MCP-1-2518A/G polymorphism and uveitis risk is not reached yet.Objective This study was to comprehensively investigate the correlation between MCP-1-2518A/G polymorphism and uveitis susceptibility.Methods General searches of electronic database including PubMed,Embase,Web of Science,CNKI,VIP,Wanfang database and China biomedical literature database (CBD) were performed to retrieve published case-control studies regarding the association between MCP-1-2518A/G polymorphism and uveitis risk.The data were screened according to the inclusion and exclusion criteria and extracted,and the quality of included studies was evaluated.The pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated.Publication bias and sensitivity analysis were also assessed.All statistical analyses were conducted with RevMan 5.2 and Stata 12.0 software.Results A total of 8 eligible case-control studies involving 1 197 cases and 1 570 controls were included in the Meta-analysis.The results showed no significant association of MCP-1-2518A/G polymorphism with uveitis susceptibility in the G vs.A,GG vs.AA and GG vs.AG+AA models (all at P>0.05).MCP-1-2518A/G polymorphism was found to be significantly associated with uveitis risk in the GG+AG vs.AA model (P =0.01,OR =1.25,95% CI:1.06-1.48),while no significant association was found by the sensitive analysis (GG + AG vs.AA:P =0.19,OR =1.16,95% CI:0.93-1.45).The subgroup analysis by uveitis types revealed that the individuals carrying allele-G or GG genotype harbored a significantly increased risk for anterior uveitis (G vs.A:P=0.01,OR=1.49,95% CI:1.16-1.90;GG vs.AA:P=0.01,OR=2.09,95% CI:1.21-3.61;GG+AG vs.AA:P=0.01,OR=1.58,95% CI:1.12-2.23;GG vs.AG+AA:P=0.01,OR=1.78,95% CI:1.12-2.83).The individuals with

  17. Aging and serum MCP-1 are associated with gut microbiome composition in a murine model.

    Science.gov (United States)

    Conley, Melissa N; Wong, Carmen P; Duyck, Kyle M; Hord, Norman; Ho, Emily; Sharpton, Thomas J

    2016-01-01

    Introduction. Age is the primary risk factor for major human chronic diseases, including cardiovascular disorders, cancer, type 2 diabetes, and neurodegenerative diseases. Chronic, low-grade, systemic inflammation is associated with aging and the progression of immunosenescence. Immunosenescence may play an important role in the development of age-related chronic disease and the widely observed phenomenon of increased production of inflammatory mediators that accompany this process, referred to as "inflammaging." While it has been demonstrated that the gut microbiome and immune system interact, the relationship between the gut microbiome and age remains to be clearly defined, particularly in the context of inflammation. The aim of our study was to clarify the associations between age, the gut microbiome, and pro-inflammatory marker serum MCP-1 in a C57BL/6 murine model. Results. We used 16S rRNA gene sequencing to profile the composition of fecal microbiota associated with young and aged mice. Our analysis identified an association between microbiome structure and mouse age and revealed specific groups of taxa whose abundances stratify young and aged mice. This includes the Ruminococcaceae, Clostridiaceae, and Enterobacteriaceae. We also profiled pro-inflammatory serum MCP-1 levels of each mouse and found that aged mice exhibited elevated serum MCP-1, a phenotype consistent with inflammaging. Robust correlation tests identified several taxa whose abundance in the microbiome associates with serum MCP-1 status, indicating that they may interact with the mouse immune system. We find that taxonomically similar organisms can exhibit differing, even opposite, patterns of association with the host immune system. We also find that many of the OTUs that associate with serum MCP-1 stratify individuals by age. Discussion. Our results demonstrate that gut microbiome composition is associated with age and the pro-inflammatory marker, serum MCP-1. The correlation between age

  18. Research of MCP-1 expression in rat's retina injured by ischemia-reperfusion%MCP-1在大鼠视网膜缺血再灌注损伤中的表达及意义研究

    Institute of Scientific and Technical Information of China (English)

    游志鹏; 姜德咏; 李国栋; 赵宏伟

    2003-01-01

    目的了解MCP-1在大鼠视网膜缺血再灌注损伤中的表达及意义.方法建立大鼠视网膜缺北血再灌注模型,以SABC法检测MCP-1在视网膜中的表达,统计学分析.结果MCP-1在视网膜缺血再灌注6 h开始表达,第24小时达到最高峰,48 h开始表达减弱.结论MCP-1在视网膜缺血再灌注损伤中起重要作用.%Objective:The retina ischemia- reperfusion injury is caused by many factors. A lot of cell factors take part in it. Many researches suggest MCP - 1 has special effect on leukocyte and lymphocyte. The research try to study the effect of MCP - 1 in rat's retina ischemia- reperfusion injury. Methods: To employ the rat's retina ischemia- reperfusion model and use SABC method to test the expression of MCP- 1 on retina. Results: There was no MCP - 1 expressed in retina after ischemia- reperfusion injury for one hour. MCP- 1 began to express in retina after ischemia- reperfusion injury for six hours, and expressed at most after ischemia- reperfusion injury for 24 hours. Then it began to decrease in 48 hours after ischemia - repeffusion injury, but it still expressed in retina in seventy- two hours after ischemia- reperfusion injury. Conclusions: MCP- 1 plays an important role in rat's retina ischemia- reperfusion injury.

  19. Vascular endothelial growth factor (VEGF and monocyte chemoattractant protein (MCP-1 levels unaltered in symptomatic atherosclerotic carotid plaque patients from North India

    Directory of Open Access Journals (Sweden)

    Dheeraj eKhurana

    2013-04-01

    Full Text Available We aimed to identify the role of vascular endothelial growth factor(VEGF and monocyte chemoattractant protein(MCP-1 as a serum biomarker of symptomatic carotid atherosclerotic plaque in North Indian population. Individuals with symptomatic carotid atherosclerotic plaque have high risk of ischemic stroke. Previous studies from western countries have shown an association between VEGF and MCP-1 levels and the incidence of ischemic stroke. In this study, venous blood from 110 human subjects was collected, 57 blood samples of which were obtained from patients with carotid plaques, 38 neurological controls without carotid plaques and another 15 healthy controls who had no history of serious illness. Serum VEGF and MCP-1 levels were measured using commercially available enzyme-linked immunosorbent assay(ELISA. We also correlated the data clinically and carried out risk factor analysis based on the detailed questionnaire obtained from each patient. For risk factor analysis, a total of 70 symptomatic carotid plaque cases and equal number of age and sex matched healthy controls were analyzed. We found that serum VEGF levels in carotid plaque patients did not show any significant change when compared to either of the controls. Similarly, there was no significant upregulation of monocyte chemoattractant protein-1 in the serum of these patients. The risk factor analysis revealed that hypertension, diabetes, and physical inactivity were the main correlates of carotid atherosclerosis(p<0.05. Prevalence of patients was higher residing in urban areas as compared to rural region. We also found that patients coming from mountaineer region were relatively less vulnerable to cerebral atherosclerosis as compared to the ones residing at plain region. We conclude that the pathogenesis of carotid plaques may progress independent of these inflammatory molecules. In parallel, risk factor analysis indicates hypertension, diabetes and sedentary lifestyle as the most

  20. 5, 8, 11, 14-eicosatetraynoic acid suppresses CCL2/MCP-1 expression in IFN-γ-stimulated astrocytes by increasing MAPK phosphatase-1 mRNA stability

    Directory of Open Access Journals (Sweden)

    Lee Jee

    2012-02-01

    Full Text Available Abstract Background The peroxisome proliferator-activated receptor (PPAR-α activator, 5,8,11,14-eicosatetraynoic acid (ETYA, is an arachidonic acid analog. It is reported to inhibit up-regulation of pro-inflammatory genes; however, its underlying mechanism of action is largely unknown. In the present study, we focused on the inhibitory action of ETYA on the expression of the chemokine, CCL2/MCP-1, which plays a key role in the initiation and progression of inflammation. Methods To determine the effect of ETYA, primary cultured rat astrocytes and microglia were stimulated with IFN-γ in the presence of ETYA and then, expression of CCL2/MCP-1 and MAPK phosphatase (MKP-1 were determined using RT-PCR and ELISA. MKP-1 mRNA stability was evaluated by treating actinomycin D. The effect of MKP-1 and human antigen R (HuR was analyzed by using specific siRNA transfection system. The localization of HuR was analyzed by immunocytochemistry and subcellular fractionation experiment. Results We found that ETYA suppressed CCL2/MCP-1 transcription and secretion of CCL2/MCP-1 protein through up-regulation of MKP-1mRNA levels, resulting in suppression of c-Jun N-terminal kinase (JNK phosphorylation and activator protein 1 (AP1 activity in IFN-γ-stimulated brain glial cells. Moreover, these effects of ETYA were independent of PPAR-α. Experiments using actinomycin D revealed that the ETYA-induced increase in MKP-1 mRNA levels reflected an increase in transcript stability. Knockdown experiments using small interfering RNA demonstrated that this increase in MKP-1 mRNA stability depended on HuR, an RNA-binding protein known to promote enhanced mRNA stability. Furthermore, ETYA-induced, HuR-mediated mRNA stabilization resulted from HuR-MKP-1 nucleocytoplasmic translocation, which served to protect MKP-1 mRNA from the mRNA degradation machinery. Conclusion ETYA induces MKP-1 through HuR at the post-transcriptional level in a receptor-independent manner. The mechanism

  1. MCP-1对培养的人肾小球内皮细胞表达ICAM-1的影响%Effects of MCP-1 on expression of ICAM-1 in cultured humanglomerular endothelial cell

    Institute of Scientific and Technical Information of China (English)

    丁涵露; 朱妙珍; 张建国; 罗向东; 梁光萍

    2001-01-01

    目的研究单核细胞趋化蛋白-1(MCP-1)对培养的人肾小球内皮细胞(HUGEC)表达细胞间粘附分子-1(ICAM-1)的影响.方法采用细胞ELISA法. 结果①培养的HUGEC表面有少量ICAM-1表达,在10 ng/mL MCP-1刺激后ICAM-1表达量增多(P<0.05),6 h即有ICAM-1表达增强,12 h达高峰,不同浓度的MCP-1(10、20、40 ng/mL)刺激HUGEC18 h后,ICAM-1表达与对照组比较差异显著(P<0.01);②加入抗MCP-1抗体后,ICAM-1表达量下降,与对照组比较无差异(P>0.05). 结论 MCP-1可刺激HUGEC表达ICAM-1增加.

  2. Detection of early atherosclerosis with radiolabeled monocyte chemoattractant protein-1 in prediabeteic Zucker rats

    Energy Technology Data Exchange (ETDEWEB)

    Blankenberg, F.G. [Div. of Pediatric Radiology, Stanford, CA (United States); Wen, P.; Dai, M.; Zhu, D.; Panchal, S.N.; Valantine, H.A. [Division of Cardiovascular Medicine, Department of Medicine, Stanford, California (United States); Tait, J.F. [Dept. of Laboratory Medicine, Univ. of Washington, Seattle (United States); Post, A.M.; Strauss, H.W. [Div. of Nuclear Medicine, Stanford Univ., CA (United States)

    2001-12-01

    Background: Migration of monocytes into the arterial wall is an early finding of atherosclerosis. Monocytes are attracted to sites of vascular endothelial cell injury, the initiating event in the development of atheromatous disease, by a chemokine known as monocyte chemoattractant protein-1 (MCP-1). Injured vascular endothelial and smooth muscle cells selectively secrete MCP-1. Objective: This study was performed to determine if radiolabeled MCP-1 would co-localize at sites of monocyte/macrophage concentration in an experimental model of transplant-induced vasculopathy in diabetic animals. Materials and methods: Hearts from 3-month-old male Zucker rats, heterozygote (Lean) or homozygote (Fat) for the diabetes-associated gene fa, were transplanted into the abdomens of genetically matched recipients. Lean and Fat animals were then fed normal or high-fat diets for 90 days. Results: At 90 days significant increases (P < 0.013) of MCP-1 graft uptake were seen at imaging and confirmed on scintillation gamma well counting studies in Lean (n = 5) and Fat (n = 12) animals, regardless of diet, 400 % and 40 %, above control values, respectively. MCP-1 uptake of native and grafted hearts correlated with increased numbers of perivascular macrophages (P < 0.02), as seen by immunostaining with an antibody specific for macrophages (ED 2). Conclusion: Radiolabeled MCP-1 can detect abnormally increased numbers of perivascular mononuclear cells in native and grafted hearts in prediabetic rats. MCP-1 may be useful in the screening of diabetic children for early atherosclerotic disease. (orig.)

  3. Detection of early atherosclerosis with radiolabeled monocyte chemoattractant protein-1 in prediabeteic Zucker rats

    International Nuclear Information System (INIS)

    Background: Migration of monocytes into the arterial wall is an early finding of atherosclerosis. Monocytes are attracted to sites of vascular endothelial cell injury, the initiating event in the development of atheromatous disease, by a chemokine known as monocyte chemoattractant protein-1 (MCP-1). Injured vascular endothelial and smooth muscle cells selectively secrete MCP-1. Objective: This study was performed to determine if radiolabeled MCP-1 would co-localize at sites of monocyte/macrophage concentration in an experimental model of transplant-induced vasculopathy in diabetic animals. Materials and methods: Hearts from 3-month-old male Zucker rats, heterozygote (Lean) or homozygote (Fat) for the diabetes-associated gene fa, were transplanted into the abdomens of genetically matched recipients. Lean and Fat animals were then fed normal or high-fat diets for 90 days. Results: At 90 days significant increases (P < 0.013) of MCP-1 graft uptake were seen at imaging and confirmed on scintillation gamma well counting studies in Lean (n = 5) and Fat (n = 12) animals, regardless of diet, 400 % and 40 %, above control values, respectively. MCP-1 uptake of native and grafted hearts correlated with increased numbers of perivascular macrophages (P < 0.02), as seen by immunostaining with an antibody specific for macrophages (ED 2). Conclusion: Radiolabeled MCP-1 can detect abnormally increased numbers of perivascular mononuclear cells in native and grafted hearts in prediabetic rats. MCP-1 may be useful in the screening of diabetic children for early atherosclerotic disease. (orig.)

  4. Urine Monocyte Chemoattractant Protein-1 and Lupus Nephritis Disease Activity: Preliminary Report of a Prospective Longitudinal Study

    Directory of Open Access Journals (Sweden)

    Sabah Alharazy

    2015-01-01

    Full Text Available Objective. This longitudinal study aimed to determine the urine monocyte chemoattractant protein-1 (uMCP-1 levels in patients with biopsy-proven lupus nephritis (LN at various stages of renal disease activity and to compare them to current standard markers. Methods. Patients with LN—active or inactive—had their uMCP-1 levels and standard disease activity markers measured at baseline and 2 and 4 months. Urinary parameters, renal function test, serological markers, and renal SLE disease activity index-2K (renal SLEDAI-2K were analyzed to determine their associations with uMCP-1. Results. A hundred patients completed the study. At each visit, uMCP-1 levels (pg/mg creatinine were significantly higher in the active group especially with relapses and were significantly associated with proteinuria and renal SLEDAI-2K. Receiver operating characteristic (ROC curves showed that uMCP-1 was a potential biomarker for LN. Whereas multiple logistic regression analysis showed that only proteinuria and serum albumin and not uMCP-1 were independent predictors of LN activity. Conclusion. uMCP-1 was increased in active LN. Although uMCP-1 was not an independent predictor for LN activity, it could serve as an adjunctive marker when the clinical diagnosis of LN especially early relapse remains uncertain. Larger and longer studies are indicated.

  5. Insulin resistance is associated with MCP1-mediated macrophage accumulation in skeletal muscle in mice and humans.

    Directory of Open Access Journals (Sweden)

    David Patsouris

    Full Text Available Inflammation is now recognized as a major factor contributing to type 2 diabetes (T2D. However, while the mechanisms and consequences associated with white adipose tissue inflammation are well described, very little is known concerning the situation in skeletal muscle. The aim of this study was to investigate, in vitro and in vivo, how skeletal muscle inflammation develops and how in turn it modulates local and systemic insulin sensitivity in different mice models of T2D and in humans, focusing on the role of the chemokine MCP1. Here, we found that skeletal muscle inflammation and macrophage markers are increased and associated with insulin resistance in mice models and humans. In addition, we demonstrated that intra-muscular TNFα expression is exclusively restricted to the population of intramuscular leukocytes and that the chemokine MCP1 was associated with skeletal muscle inflammatory markers in these models. Furthermore, we demonstrated that exposure of C2C12 myotubes to palmitate elevated the production of the chemokine MCP1 and that the muscle-specific overexpression of MCP1 in transgenic mice induced the local recruitment of macrophages and altered local insulin sensitivity. Overall our study demonstrates that skeletal muscle inflammation is clearly increased in the context of T2D in each one of the models we investigated, which is likely consecutive to the lipotoxic environment generated by peripheral insulin resistance, further increasing MCP1 expression in muscle. Consequently, our results suggest that MCP1-mediated skeletal muscle macrophages recruitment plays a role in the etiology of T2D.

  6. Inflammatory biomarkers CRP, MCP-1, serum amyloid alpha and interleukin-18 in patients with HTN and dyslipidemia: impact of diabetes mellitus on metabolic syndrome and the effect of statin therapy.

    Science.gov (United States)

    Rabkin, Simon W; Langer, Anatoly; Ur, Ehud; Calciu, Cristina-Dana; Leiter, Lawrence A

    2013-06-01

    The objective of this study was to determine the relationship of HTN (HTN) and the inflammatory markers C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), amyloid alpha (AA) and interleukin-18 (IL-18) in persons with HTN, considering concomitant diabetes mellitus (DM) or metabolic syndrome (MS). This was a multicenter twelve-week, single-step titration, open-label study of individuals with dyslipidemia, assigned according to their initial risk assessment, to atorvastatin starting doses of 10, 20, 40 or 80 mg. In subjects with HTN (N=677) versus no HTN (N=581), there were significantly (P<0.02) higher levels of CRP, IL-18, MCP-1 and AA but not for IL-18 when combined with DM or MS, and AA or CRP when combined with MS. Systolic blood pressure significantly (P<0.02) correlated with CRP, MCP-1 and AA but not IL-18. The greatest increase in CRP was with HTN plus DM. Statin therapy produced significant dose-dependent reductions in CRP but not with similar changes in other inflammatory markers. In summary, these data suggest a complex relationship between inflammation and HTN with dyslipidemia. Although HTN is associated with an increase in these inflammatory markers, the associated conditions DM or MS lead to different patterns of increases-MCP-1 being the most consistently increased with HTN, the greatest CRP increase was with HTN and DM, and no relationship was found with IL-18 and HTN in the presence of DM or MS. In addition, there are different responses to statins depending on the nature of the inflammatory marker.

  7. Signal pathways underlying homocysteine-induced production of MCP-1 and IL-8 in cultured human whole blood

    Institute of Scientific and Technical Information of China (English)

    Xiao-kun ZENG; You-fei GUAN; Daniel G REMICK; Xian WANG

    2005-01-01

    Aim: To elucidate the mechanisms underlying homocysteine (Hcy)-induced chemokine production. Methods: Human whole blood was pretreated with inhibitors of calmodulin (CaM), protein kinase C (PKC), protein tyrosine kinase(PTK), mitogen-activated protein kinase (MAPK), and NF-κB and activators of PPARγ for 60 min followed by incubation with Hcy 100 μmol/L for 32 h. The levels of mitogen chemokine protein (MCP)-1 and interleukin-8 (IL-8) were determined by enzyme-linked immunosorbant assay (ELISA). Results: Inhibitors of PKC (calphostin C, 50-500 nmol/L and RO-31-8220, 10-100 nmol/L), CaM(W7, 28-280 μmol/L), ERK1/2 MAPK (PD 98059, 2-20 μmol/L), p38 MAPK(SB 203580, 0.6-6 μmol/L), JNK MAPK (curcumin, 2-10 μmol/L), and NF-κB(PDTC, 10-100 nmol/L) markedly reduced Hcy 100 μmol/L-induced production of MCP-1 and IL-8 in human cultured whole blood, but the inhibitors of PTK(genistein, 2.6-26 μmol/L and tyrphostin, 0.5-5 μmol/L) had no obvious effect on MCP-1 and IL-8 production. PPARγ activators (ciglitazone 30 μmol/L and troglitazone 10 μmol/L) depressed the Hcy-induced MCP-1 production but not IL-8 production in the cultured whole blood. Conclusion: Hcy-induced MCP-1 and IL-8 production is mediated by activated signaling pathways such as PKC,CaM, MAPK, and NF-κB. Our results not only provide clues for the signal transduction pathways mediating Hcy-induced chemokine production, but also offer a plausible explanation for a pathogenic role of hyperhomocysteinemia in these diseases.

  8. Psoriasin: a novel chemotactic protein

    DEFF Research Database (Denmark)

    Jinquan, T; Vorum, H; Larsen, C G;

    1996-01-01

    inflammatory protein for CD4+ T lymphocytes and neutrophils at concentrations of about 10(-11) M. Psoriasin is not structurally related to the alpha or the beta chemokine subfamilies or to lymphotactin, a member of a newly described class of chemokines. Thus, we have observed a chemotactic protein outside...... the chemokine subfamilies that could be an important new inflammatory mediator. Udgivelsesdato: 1996-Jul...

  9. Urine Monocyte Chemoattractant Protein-1 Is an Independent Predictive Factor of Hospital Readmission and Survival in Cirrhosis

    Science.gov (United States)

    Graupera, Isabel; Solà, Elsa; Fabrellas, Núria; Moreira, Rebeca; Solé, Cristina; Huelin, Patricia; de la Prada, Gloria; Pose, Elisa; Ariza, Xavier; Risso, Alessandro; Albertos, Sonia; Morales-Ruiz, Manuel; Jiménez, Wladimiro; Ginès, Pere

    2016-01-01

    MCP-1 (monocyte chemoattractant protein-1) is a proinflammatory cytokine involved in chemotaxis of monocytes. In several diseases, such as acute coronary syndromes and heart failure, elevated MCP-1 levels have been associated with poor outcomes. Little is known about MCP-1 in cirrhosis. AIM: To investigate the relationship between MCP-1 and outcome in decompensated cirrhosis. METHODS: Prospective study of 218 patients discharged from hospital after an admission for complications of cirrhosis. Urine and plasma levels of MCP-1 and other urine proinflammatroy biomarkers: osteopontin(OPN), trefoil-factor3 and liver-fatty-acid-binding protein were measured at admission. Urine non-inflammatory mediators cystatin-C, β2microglobulin and albumin were measured as control biomarkers. The relationship between these biomarkers and the 3-month hospital readmission, complications of cirrhosis, and mortality were assessed. RESULTS: 69 patients(32%) had at least one readmission during the 3-month period of follow-up and 30 patients died(14%). Urine MCP-1 and OPN levels, were associated with 3-month probability of readmission (0.85 (0.27–2.1) and 2003 (705–4586) ug/g creat vs 0.47 (0.2–1.1) and 1188 (512–2958) ug/g creat, in patients with and without readmission, respectively; phepatic encephalopathy, bacterial infections or AKI. Urine MCP-1 was an independent predictive factor of hospital readmission and combined end-point of readmission or dead at 3 months. Plasma levels of MCP-1 did not correlated with outcomes. CONCLUSION: Urine, but not plasma, MCP-1 levels are associated with hospital readmission, development of complications of cirrhosis, and mortality. These results suggest that in cirrhosis there is an inflammatory response that is associated with poor outcomes. PMID:27359339

  10. Aumento da expressão do MCP-1 coroidal e escleral em modelo experimental de hipercolesterolemia

    Directory of Open Access Journals (Sweden)

    Rogil José de Almeida Torres

    2012-02-01

    Full Text Available OBJETIVO: O objetivo deste trabalho é demonstrar experimentalmente que a dieta rica em colesterol provoca aumento da expressão da MCP-1 na coroide e esclera. MÉTODO: Coelhos New Zealand foram organizados em dois grupos: GN (grupo dieta normal, composto por 8 coelhos (8 olhos, recebeu ração padrão para coelhos, durante 4 semanas; GH (grupo hipercolesterolêmico, composto por 13 coelhos (13 olhos, recebeu dieta rica em colesterol a 1% por 8 semanas. Foi realizada a dosagem sérica de colesterol total, triglicerídeos, HDL colesterol, glicemia de jejum no início do experimento e no momento da eutanásia. Ao final da 8ª semana para o GH e 4ª semana para o GN foi realizada a eutanásia dos animais e os olhos foram submetidos à análise imuno-histoquímica com o anticorpo anti-MCP-1. RESULTADOS: A dieta provocou significativo aumento do colesterol total e triglicerídeos do GH em relação ao GN (p<0,001. Houve significativo aumento da expressão da MCP-1 na coroide e esclera dos animais do GH em relação ao GN (p<0,001. CONCLUSÃO: Este estudo demonstrou que a dieta hipercolesterolêmica em coelhos induz ao aumento da expressão do MCP-1 na coroide e esclera.

  11. The expression of chemokine MCP-1 in colorectal carcinoma and its relationship to the infiltration of macrophage%结直肠癌趋化因子MCP-1的表达及其与巨噬细胞浸润的关系

    Institute of Scientific and Technical Information of China (English)

    杨春康; 陈道达; 黄凯

    2006-01-01

    Objective: To study the expression of MCP-1 in colorectal carcinoma and its relationship to the infiltration of the macrophage and to the biological behaviour of infiltration and metastasis of colorectal carcinoma.Methods: The expression of the MCP-1 mRNAwas assessed in colorectal carcinoma collected freshly from surgical specimen by RT-PCR and the expression of the MCP-1 protein was assessed in colorectal carcinoma collected from surgical specimen by immunohistochemistry.The tumor infiltrating cell and macrophage were also investigated by immunohistochemistry.Results: All the 12 specimens of colorectal carcinoma detected by RT-PCR expressed the MCP-1 mRNA; MCP-1 protein was detected in 90% (36/40) cases of the tumor; The expression of the MCP-1 protein in colorectal carcinoma correlated negatively with its state of metastasis and the Dukes' stage.But a postive correlation was found between the expression of MCP-1 and the infiltrated macrophage.The stronger expression of MCP-1,the more number of the infiltrated macrophage.Conclusion: The expression of chemokine MCP-1 in colorectal carcinoma may influence its biological behaviour of infiltration and metastasis,and can attract the immuno-cell to the local of the tumor,such as Macrophage.

  12. Identification of serum monocyte chemoattractant protein-1 and prolactin as potential tumor markers in hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Who-Whong Wang

    Full Text Available Early diagnosis of hepatocellullar carcinoma (HCC remains a challenge. The current practice of serum alpha-fetoprotein (AFP measurement is inadequate. Here we utilized a proteomic approach to identify novel serum biomarkers for distinguishing HCC patients from non-cancer controls. We profiled the serum proteins in a group of 58 resectable HCC patients and 11 non-HCC chronic hepatitis B (HBV carrier samples from the Singapore General Hospital (SGH using the RayBio® L-Series 507 Antibody Array and found 113 serum markers that were significantly modulated between HCC and control groups. Selected potential biomarkers from this list were quantified using a multiplex sandwich enzyme-linked immunosorbent assay (ELISA array in an expanded SGH cohort (126 resectable HCC patients and 115 non-HCC chronic HBV carriers (NC group, confirming that serum prolactin and monocyte chemoattractant protein-1 (MCP-1 were significantly upregulated in HCC patients. This finding of serum MCP-1 elevation in HCC patients was validated in a separate cohort of serum samples from the Mochtar Riady Institute for Nanotechnology, Indonesia (98 resectable HCC, 101 chronic hepatitis B patients and 100 asymptomatic HBV/HCV carriers by sandwich ELISA. MCP-1 and prolactin levels were found to correlate with AFP, while MCP-1 also correlated with disease stage. Subsequent receiver operating characteristic (ROC analysis of AFP, prolactin and MCP-1 in the SGH cohort and comparing their area under the ROC curve (AUC indicated that neither prolactin nor MCP-1 on their own performed better than AFP. However, the combination of AFP+MCP-1 (AUC, 0.974 had significantly superior discriminative ability than AFP alone (AUC, 0.942; p<0.001. In conclusion, prolactin and MCP-1 are overexpressed in HCC and are conveniently quantifiable in patients' sera by ELISA. MCP-1 appears to be a promising complementary biomarker for HCC diagnosis and this MCP-1+AFP model should be further evaluated as

  13. Identification of serum monocyte chemoattractant protein-1 and prolactin as potential tumor markers in hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Who-Whong; Ang, Soo Fan; Kumar, Rajneesh; Heah, Charmain; Utama, Andi; Tania, Navessa Padma; Li, Huihua; Tan, Sze Huey; Poo, Desmond; Choo, Su Pin; Chow, Wan Cheng; Tan, Chee Kiat; Toh, Han Chong

    2013-01-01

    Early diagnosis of hepatocellullar carcinoma (HCC) remains a challenge. The current practice of serum alpha-fetoprotein (AFP) measurement is inadequate. Here we utilized a proteomic approach to identify novel serum biomarkers for distinguishing HCC patients from non-cancer controls. We profiled the serum proteins in a group of 58 resectable HCC patients and 11 non-HCC chronic hepatitis B (HBV) carrier samples from the Singapore General Hospital (SGH) using the RayBio® L-Series 507 Antibody Array and found 113 serum markers that were significantly modulated between HCC and control groups. Selected potential biomarkers from this list were quantified using a multiplex sandwich enzyme-linked immunosorbent assay (ELISA) array in an expanded SGH cohort (126 resectable HCC patients and 115 non-HCC chronic HBV carriers (NC group)), confirming that serum prolactin and monocyte chemoattractant protein-1 (MCP-1) were significantly upregulated in HCC patients. This finding of serum MCP-1 elevation in HCC patients was validated in a separate cohort of serum samples from the Mochtar Riady Institute for Nanotechnology, Indonesia (98 resectable HCC, 101 chronic hepatitis B patients and 100 asymptomatic HBV/HCV carriers) by sandwich ELISA. MCP-1 and prolactin levels were found to correlate with AFP, while MCP-1 also correlated with disease stage. Subsequent receiver operating characteristic (ROC) analysis of AFP, prolactin and MCP-1 in the SGH cohort and comparing their area under the ROC curve (AUC) indicated that neither prolactin nor MCP-1 on their own performed better than AFP. However, the combination of AFP+MCP-1 (AUC, 0.974) had significantly superior discriminative ability than AFP alone (AUC, 0.942; p<0.001). In conclusion, prolactin and MCP-1 are overexpressed in HCC and are conveniently quantifiable in patients' sera by ELISA. MCP-1 appears to be a promising complementary biomarker for HCC diagnosis and this MCP-1+AFP model should be further evaluated as potential

  14. Homocysteine induces production of monocyte chemoattractant protein-1 and interleukin-8 in cultured human whole blood

    Institute of Scientific and Technical Information of China (English)

    Xiao-kun ZENG; Daniel G REMICK; Xian WANG

    2004-01-01

    AIM: To investigate whether increased plasma L-homocysteine (Hcy) level could promote monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) in cultured whole blood. METHODS: Human whole blood or different type of peripheral blood cells from health volunteers were incubated with Hcy and/or the inhibitors. MCP- 1 and IL-8 level were measured by ELISA assay. RESULTS: Hcy 10-1000 μmol/L induced production of MCP-1 and IL-8 in cultured human whole blood (P<0.05). The major cellular source of these chemokines comed from monocytes.Meanwhile,Hcy also promoted the upregulation of MPO level even at the 10 μmol/L in the cultured whole blood.secretion in cultured human whole blood, especially in monocytes via oxidative stress mechanism.

  15. Comparative effect of genistein and daidzein on the expression of MCP-1, eNOS, and cell adhesion molecules in TNF-α-stimulated HUVECs

    OpenAIRE

    Cho, Hye Yeon; Park, Chung Mu; Kim, Mi Jeong; Chinzorig, Radnaabazar; Cho, Chung Won; Song, Young Sun

    2011-01-01

    We compared the effects of genistein and daidzein on the expression of chemokines, cell adhesion molecules (CAMs), and endothelial nitric oxide synthase (eNOS) in tumor necrosis factor (TNF)-α-stimulated human umbilical vascular endothelial cells (HUVECs). TNF-α exposure significantly increased expression of monocyte chemoattractant protein (MCP)-1, vascular adhesion molecule (VCAM)-1, and intercellular adhesion molecule-1. Genistein significantly decreased MCP-1 and VCAM-1 production in a do...

  16. Effects of Tumor Necrosis Factor-α on Podocyte Expression of Monocyte Chemoattractant Protein-1 and in Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Choon Hee Chung

    2015-02-01

    Full Text Available Background/Aims: Tumor necrosis factor (TNF-α is believed to play a role in diabetic kidney disease. This study explores the specific effects of TNF-α with regard to nephropathy-relevant parameters in the podocyte. Methods: Cultured mouse podocytes were treated with recombinant TNF-α and assayed for production of monocyte chemoattractant protein-1 (MCP-1 by enzyme-linked immunosorbent assay (ELISA. TNF-α signaling of MCP-1 was elucidated by antibodies against TNF receptor (TNFR 1 or TNFR2 or inhibitors of nuclear factor-kappaB (NF-κB, phosphatidylinositol 3-kinase (PI3K or Akt. In vivo studies were done on male db/m and type 2 diabetic db/db mice. Levels of TNF-α and MCP-1 were measured by RT-qPCR and ELISA in the urine, kidney and plasma of the two cohorts and correlated with albuminuria. Results: Podocytes treated with TNF-α showed a robust increase (∼900% in the secretion of MCP-1, induced in a dose- and time-dependent manner. Signaling of MCP-1 expression occurred through TNFR2, which was inducible by TNF-α ligand, but did not depend on TNFR1. TNF-α then proceeded via the NF-κB and the PI3K/Akt systems, based on the effectiveness of the inhibitors of those pathways. For in vivo relevance to diabetic kidney disease, TNF-α and MCP-1 levels were found to be elevated in the urine of db/db mice but not in the plasma. Conclusion: TNF-α potently stimulates podocytes to produce MCP-1, utilizing the TNFR2 receptor and the NF-κB and PI3K/Akt pathways. Both TNF-α and MCP-1 levels were increased in the urine of diabetic db/db mice, correlating with the severity of diabetic albuminuria.

  17. The therapeutic effect of monocyte chemoattractant protein-1 delivered by an electrospun scaffold for hyperglycemia and nephrotic disorders

    Directory of Open Access Journals (Sweden)

    Yong C

    2014-02-01

    Full Text Available Cai Yong,2,* Zhengxin Wang,1,* Xing Zhang,3 Xiaomin Shi,1 Zhijia Ni,1 Hong Fu,1 Guoshan Ding,1 Zhiren Fu,1 Hao Yin1,3 1Department of Surgery, Organ Transplant Center, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China; 2Department of Transplantation, First Affiliated Hospital of Wenzhou Medical College, Wenzhou, People's Republic of China; 3Department of Surgery, University of Chicago, Chicago, IL, USA *These authors contributed equally to this article Abstract: Here, we investigated in diabetic mice the therapeutic effect of monocyte chemoattractant protein-1 (MCP-1, locally delivered by an electrospun scaffold, on transplanted islets. This therapeutic scheme is expected to exert a synergistic effect to ameliorate hyperglycemia and its associated nephrotic disorders. The cumulative amount of MCP-1 released from the scaffold in vitro within a 3-week window was 267.77±32.18 ng, without a compromise in bioactivity. After 8 weeks following the transplantation, the islet population stimulated by MCP-1 was 35.14%±7.23% larger than the non-stimulated islet population. Moreover, MCP-1 increased concentrations of blood insulin and C-peptide 2 by 49.83%±5.29% and 43.49%±9.21%, respectively. Consequently, the blood glucose concentration in the MCP-1 group was significantly lower than that in the control group at week 2 post-surgery. MCP-1 also enhanced the tolerance of sudden oral glucose challenge. The rapid decrease of blood creatinine, urine creatinine, and blood urea nitrogen suggested that the recovery of renal functions compromised by hyperglycemia could also be attributed to MCP-1. Our study shed new light on a synergistic strategy to alleviate hyperglycemia and nephrotic disorders in diabetic patients. Keywords: MCP-1, electrospinning, islet transplantation, diabetes

  18. TNF-{alpha} similarly induces IL-6 and MCP-1 in fibroblasts from colorectal liver metastases and normal liver fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, Lars, E-mail: lars.mueller@uksh-kiel.de [Department of General and Thoracic Surgery, University Hospital of Schleswig-Holstein (Germany); Seggern, Lena von [Department of Hepatobiliary Surgery and Solid Organ Transplantation, University Hospital Hamburg-Eppendorf, Hamburg (Germany); Schumacher, Jennifer; Goumas, Freya; Wilms, Christian; Braun, Felix; Broering, Dieter C. [Department of General and Thoracic Surgery, University Hospital of Schleswig-Holstein (Germany)

    2010-07-02

    Cancer-associated fibroblasts (CAFs) represent the predominant cell type of the neoplastic stroma of solid tumors, yet their biology and functional specificity for cancer pathogenesis remain unclear. We show here that primary CAFs from colorectal liver metastases express several inflammatory, tumor-enhancing factors, including interleukin (IL)-6 and monocyte-chemoattractant protein (MCP)-1. Both molecules were intensely induced by TNF-{alpha} on the transcript and protein level, whereas PDGF-BB, TGF-{beta}1 and EGF showed no significant effects. To verify their potential specialization for metastasis progression, CAFs were compared to fibroblasts from non-tumor liver tissue. Interestingly, these liver fibroblasts (LFs) displayed similar functions. Further analyses revealed a comparable up-regulation of intercellular adhesion molecule-1 (ICAM-1) by TNF-{alpha}, and of alpha-smooth muscle actin, by TGF-{beta}1. Moreover, the proliferation of both cell types was induced by PDGF-BB, and CAFs and LFs displayed an equivalent migration towards HT29 colon cancer cells in Boyden chamber assays. In conclusion, colorectal liver metastasis may be supported by CAFs and resident fibroblastic cells competent to generate a prometastatic microenvironment through inflammatory activation of IL-6 and MCP-1.

  19. Urine Monocyte Chemoattractant Protein-1 Is an Independent Predictive Factor of Hospital Readmission and Survival in Cirrhosis.

    Directory of Open Access Journals (Sweden)

    Isabel Graupera

    Full Text Available MCP-1 (monocyte chemoattractant protein-1 is a proinflammatory cytokine involved in chemotaxis of monocytes. In several diseases, such as acute coronary syndromes and heart failure, elevated MCP-1 levels have been associated with poor outcomes. Little is known about MCP-1 in cirrhosis.To investigate the relationship between MCP-1 and outcome in decompensated cirrhosis.Prospective study of 218 patients discharged from hospital after an admission for complications of cirrhosis. Urine and plasma levels of MCP-1 and other urine proinflammatroy biomarkers: osteopontin(OPN, trefoil-factor3 and liver-fatty-acid-binding protein were measured at admission. Urine non-inflammatory mediators cystatin-C, β2microglobulin and albumin were measured as control biomarkers. The relationship between these biomarkers and the 3-month hospital readmission, complications of cirrhosis, and mortality were assessed.69 patients(32% had at least one readmission during the 3-month period of follow-up and 30 patients died(14%. Urine MCP-1 and OPN levels, were associated with 3-month probability of readmission (0.85 (0.27-2.1 and 2003 (705-4586 ug/g creat vs 0.47 (0.2-1.1 and 1188 (512-2958 ug/g creat, in patients with and without readmission, respectively; p<0.05; median (IQR. Furthermore, urine levels of MCP-1 were significantly associated with mortality (1.01 (1-3.6 vs 0.5 (0.2-1.1 μg/g creat, in dead and alive patients at 3 months; p<0.05. Patients with higher levels of urine MCP-1 (above percentile 75th had higher probability of development of hepatic encephalopathy, bacterial infections or AKI. Urine MCP-1 was an independent predictive factor of hospital readmission and combined end-point of readmission or dead at 3 months. Plasma levels of MCP-1 did not correlated with outcomes.Urine, but not plasma, MCP-1 levels are associated with hospital readmission, development of complications of cirrhosis, and mortality. These results suggest that in cirrhosis there is an

  20. The relationship of urinary MCP1、 fetuin-A expression and urinary MDA in patients with nephrolithiasis%肾结石患者尿液MCP-1、胎球蛋白-A表达与MDA的关系

    Institute of Scientific and Technical Information of China (English)

    孙春

    2015-01-01

    目的:探讨肾结石患者尿液炎症细胞因子变化以及氧化应激在结石形成中的作用.方法:选择75例草酸钙结石住院患者,随机挑选25例健康人作正常对照组.收集两组人的晨尿,分别运用ELLISA法和TBA法检测尿液中单核细胞趋化蛋白(MCP-1)、胎球蛋白-A (Fetuin-A)及丙二醛(MDA)的含量.结果:MCP-1在结石组含量为212.45 (59.24,673.50)pg/mg cr,在对照组为74.36(22.45,203.57)pg/mg cr,结石组高于对照组(P<0.05);胎球蛋白-A在结石组为320.80(42.28,1819.85)ng/mg cr,在对照组为787.94(187.03,3269.17)ng/mg cr,结石组低于对照组(P<0.05);MDA在结石组高于正常对照组(P<0.05).相关性分析:结石组尿液MCP-1和MDA不相关,r=0.045,P> 0.05;胎球蛋白-A和MDA不相关,r=-0.016,P> 0.05.结论:尿液炎症细胞因子变化和氧化应激损伤可能在肾结石形成中起作用,但是氧化应激损伤可能未参与尿液炎症细胞因子的调节.

  1. Calcitonin gene-related peptide induces proliferation and monocyte chemoattractant protein-1 expression via extracellular signal-regulated kinase activation in rat osteoblasts

    Institute of Scientific and Technical Information of China (English)

    HAN Na; ZHANG Dian-ying; WANG Tian-bing; ZHANG Pei-xun; JIANG Bao-guo

    2010-01-01

    Background Calcitonin gene-related peptide (CGRP), a sensory neuropeptide, affects osteoblast proliferation and bone formation. However, the mechanisms are not fully understood. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that stimulates the migration of monocytes and plays important roles in regulating bone remolding during fracture repair, In this study, we investigated the effects of CGRP on proliferation and MCP-1 expression in cultured rat osteoblasts.Methods Primary rat osteoblasts were isolated from fetal rats calvariae. Cells were exposed to gradient concentrations (10-9 to 10-7 mol/L) of CGRP. Protein and mRNA levels of MCP-1 were quantified by Western blotting and semiquantitative reverse transcription-polymerase chain reaction, respectively. The protein level of MCP-1 was investigated and compared in cell culture media by enzyme linked immunosorbent assay (ELISA). Phospho-extracellular signal-regulated kinase (ERK) expression was detected by Western blotting. Cell proliferative activity was measured by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) and BrdU assay. The effects of MAPK/ERK kinase (MEK)-inhibitor U0126 on CGRP-induced MCP-1 expression in primary rat osteoblasts were examined.Results CGRP effectively enhanced primary rat osteoblast proliferation and led to significant increases in the expression of MCP-1 mRNA and protein in time- and dose-dependent manners. CGRP activated the ERK pathway.Pretreatment of cultured rat osteoblasts with MEK inhibitor U0126 resulted in dose-dependent inhibitions of CGRP-induced MCP-1 mRNA and protein levels. Thus, CGRP promoted cell proliferation and stimulated MCP-1 expression in cultured rat osteoblasts.Conclusion These studies document novel links between CGRP and MCP-1 and illuminate the effects of CGRP in regulating bone remodeling.

  2. Influence of HFE variants and cellular iron on monocyte chemoattractant protein-1

    Directory of Open Access Journals (Sweden)

    Simmons Zachary

    2009-02-01

    Full Text Available Abstract Background Polymorphisms in the MHC class 1-like gene known as HFE have been proposed as genetic modifiers of neurodegenerative diseases that include neuroinflammation as part of the disease process. Variants of HFE are relatively common in the general population and are most commonly associated with iron overload, but can promote subclinical cellular iron loading even in the absence of clinically identified disease. The effects of the variants as well as the resulting cellular iron dyshomeostasis potentially impact a number of disease-associated pathways. We tested the hypothesis that the two most common HFE variants, H63D and C282Y, would affect cellular secretion of cytokines and trophic factors. Methods We screened a panel of cytokines and trophic factors using a multiplexed immunoassay in human neuroblastoma SH-SY5Y cells expressing different variants of HFE. The influence of cellular iron secretion on the potent chemokine monocyte chemoattractant protein-1 (MCP-1 was assessed using ferric ammonium citrate and the iron chelator, desferroxamine. Additionally, an antioxidant, Trolox, and an anti-inflammatory, minocycline, were tested for their effects on MCP-1 secretion in the presence of HFE variants. Results Expression of the HFE variants altered the labile iron pool in SH-SY5Y cells. Of the panel of cytokines and trophic factors analyzed, only the release of MCP-1 was affected by the HFE variants. We further examined the relationship between iron and MCP-1 and found MCP-1 secretion tightly associated with intracellular iron status. A potential direct effect of HFE is considered because, despite having similar levels of intracellular iron, the association between HFE genotype and MCP-1 expression was different for the H63D and C282Y HFE variants. Moreover, HFE genotype was a factor in the effect of minocycline, a multifaceted antibiotic used in treating a number of neurologic conditions associated with inflammation, on MCP-1

  3. Curcumin Supplementation Lowers TNF-α, IL-6, IL-8, and MCP-1 Secretion in High Glucose-Treated Cultured Monocytes and Blood Levels of TNF-α, IL-6, MCP-1, Glucose, and Glycosylated Hemoglobin in Diabetic Rats

    OpenAIRE

    Jain, Sushil K.; Rains, Justin; Croad, Jennifer; Larson, Bryon; Jones, Kimberly

    2009-01-01

    This study examined the hypothesis that curcumin supplementation decreases blood levels of IL-6, MCP-1, TNF-α, hyperglycemia, and oxidative stress by using a cell-culture model and a diabetic rat model. U937 monocytes were cultured with control (7 mM) and high glucose (35 mM) in the absence or presence of curcumin (0.01–1 μM) at 37°C for 24 h. Diabetes was induced in Sprague–Dawley rats by injection of streptozotocin (STZ) (i.p., 65 mg/kg BW). Control buffer, olive oil, or curcumin (100 mg/kg...

  4. Involvement of M3 Cholinergic Receptor Signal Transduction Pathway in Regulation of the Expression of Chemokine MOB-1, MCP-1 Genes in Pancreatic Acinar Cells

    Institute of Scientific and Technical Information of China (English)

    郑海; 陈道达; 张景輝; 田原

    2004-01-01

    Whether M3 cholinergic receptor signal transduction pathway is involved in regulation of the activation of NF-κB and the expression of chemokine MOB-1, MCP-1genes in pancreatic acinar cells was investigated. Rat pancreatic acinar cells were isolated, cultured and treated with carbachol, atropine and PDTC in vitro. The MOB-1 and MCP-1 mRNA expression was detected by using RT-PCR. The activation of NF-κB was monitored by using electrophoretic mobility shift assay.The results showed that as compared with control group, M3 cholinergic receptor agonist (103mol/L, 104-4ol/L carbachol) could induce a concentration-dependent and time-dependent increase in the expression of MOB-1, MCP-1 mRNA in pancreatic acinar cells. After treatment with 10 -3mol/L carbachol for 2 h, the expression of MOB-1, MCP-1 mRNA was strongest. The activity of NF-κB in pancreatic acinar cells was significantly increased (P<0.01) after treated with M3 cholinergic receptor agonist (10-3 mol/L carbachol) in vitro for 30 min. Either M3 cholinergic receptor antagonist (10-5 mol/L atropine) or NF-κB inhibitor (10-2 mol/L PDTC) could obviously inhibit the activation of NF-κB and the chemokine MOB-1, MCP-1 mRNA expression induced by carbachol (P <0.05). This inhibitory effect was significantly increased by atropine plus PDTC (P<0.01). The results of these studies indicated that M3 cholinergic receptor signal transduction pathway was likely involved in regulation of the expression of chemokine MOB-1 and MCP-1genes in pancreatic acinar cells in vitro through the activation of NF-κB.

  5. Nuclear NF-κB p65 in peripheral blood mononuclear cells correlates with urinary MCP-1, RANTES and the severity of type 2 diabetic nephropathy.

    Directory of Open Access Journals (Sweden)

    Bin Yi

    Full Text Available AIMS: To investigate if nuclear NF-κB p65 expression in ex vivo isolated peripheral blood mononuclear cells correlates with urinary MCP-1 or RANTES and the severity of type 2 diabetic nephropathy. METHODS: According to their urinary albumin-to-creatinine ratio (uACR, 107 patients with type 2 diabetes (eGFR >60 ml/min were divided into normal albuminuria group (DN0 group, 38 cases, microalbuminuria group (DN1 group, 38 cases, and macroalbuminuria group (DN2 group, 31 cases, compared with matched healthy normal control group (NC group, 30 cases. Nuclear NF-κB p65 protein expression levels in peripheral blood mononuclear cells were detected by western blotting. Real-time quantitative polymerase chain reaction was used to detect NF-κB p65 mRNA expression and ELISA assay was used to detect the levels of urinary MCP-1 and RANTES. RESULTS: Nuclear NF-κB p65 protein and NF-κB p65 mRNA expression levels in peripheral blood mononuclear cells, urinary MCP-1/Cr and RANTES/Cr were all significantly higher in all diabetes groups as compared with NC group. In particular, the increase of nuclear NF-κB p65 protein and NF-κB p65 mRNA expressions, urinary MCP-1/Cr and RANTES/Cr all correlated with the severity of type 2 diabetic nephropathy as indicated by the increase in uACR. Pearson correlation analysis indicated that both urinary MCP-1/Cr and RANTES/Cr were positively correlated with nuclear NF-κB p65 protein or NF-κB p65 mRNA levels. Stepwise multiple regression analysis showed that nuclear NF-κB p65 protein or NF-κB p65 mRNA was an independent variable for urinary MCP-1/Cr, and MCP-1/Cr and RANTES/Cr were two independent variables for uACR. CONCLUSION: Our research demonstrates that nuclear NF-κB p65 protein and mRNA expressions in ex vivo isolated peripheral blood mononuclear cells well correlate with urinary MCP-1/Cr, RANTES/Cr and the severity of type 2 diabetic nephropathy.

  6. Olmesartan inhibits the expression of monocyte chemoattractant protein-1 and tumor necrosis factor-α and improves vascular remodeling after vascular injury in mouse

    Institute of Scientific and Technical Information of China (English)

    李震; 陈小东; 倪少凯; 李建文; 林木生

    2004-01-01

    Objective: To investigate the neointima formation and the expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) in cuff-induced vascular injury in mouse model, and to examine the effect of angiotensin II type 1 receptor (AT1) blocker, olmesartan, on MCP-1 and TNF-α expression and consequently vascular remodeling.Methods: Vascular injury was induced by polyethylene cuff-placement around the mouse femoral artery. Some mice were treated with AT1 receptor blocker, olmesartan, at the dose of 3 mg*kg-1*day-1 with an osmotic minipump. Neointima formation and the proliferation of vascular smooth muscle cells (VSMCs) were measured by morphometric analysis and bromodeoxyuridine (BrdU) incorporation. MCP-1 and TNF-α expression was detected by Western blot and immunohistochemical staining.Results: We observed neointima formation 14 days after cuff placement as well as VSMCs proliferation in the media and neointima. Cuff placement also induced MCP-1 and TNF-α expression in the media and neointima that the VSMCs specifically existed. Treatment of mice with olmesartan at a dose of 3 mg*kg-1*day-1, which did not influence systolic blood pressure, significantly decreased neointima formation and the proliferation of VSMCs. Olmesartan also inhibited MCP-1 and TNF-α expression in the injured arteries.Conclusions: Our results demonstrate that blockade of AT1 receptor inhibits MCP-1 and TNF-α expression and thereby improves vascular remodeling.

  7. Deficiency for the chemokine monocyte chemoattractant protein-1 aggravates tubular damage after renal ischemia/reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Ingrid Stroo

    Full Text Available Temporal expression of chemokines is a crucial factor in the regulation of renal ischemia/reperfusion (I/R injury and repair. Beside their role in the migration and activation of inflammatory cells to sites of injury, chemokines are also involved in other processes such as angiogenesis, development and migration of stem cells. In the present study we investigated the role of the chemokine MCP-1 (monocyte chemoattractant protein-1 or CCL2, the main chemoattractant for monocytes, during renal I/R injury. MCP-1 expression peaks several days after inducing renal I/R injury coinciding with macrophage accumulation. However, MCP-1 deficient mice had a significant decreased survival and increased renal damage within the first two days, i.e. the acute inflammatory response, after renal I/R injury with no evidence of altered macrophage accumulation. Kidneys and primary tubular epithelial cells from MCP-1 deficient mice showed increased apoptosis after ischemia. Taken together, MCP-1 protects the kidney during the acute inflammatory response following renal I/R injury.

  8. Interleukin-1β,Tumor Necrosis Factor-α and Lipopolysaccharide Induce Expression of Monocyte Chemoattractant Protein-1 in Calf Aortic Smooth Muscle Cells

    Institute of Scientific and Technical Information of China (English)

    MENG Feng; DENG Zhongduan; NI Juan

    2000-01-01

    To investigate whether interleukin-1β(IL-1β), tumor necrosis factor-α (TNF-α) and lipopolysaccharide (LPS) induce expression of monocyte chemoattractant protein-1 (MCP-1)mRNA and protein in calf aortic smooth muscle cells(SMCs), calf aortic SMCs were cultured by a substrate-attached explant method. The cultured SMCs were used between the third to the fifth passage. After the cells became confluent, the SMCs were exposed to 2 ng/ml IL- 1β, 20 ng/mlTNF-lα and 100 ng/ml LPS respectively, and the total RNA of SMCs which were incubated for 4h at 37℃ were extracted from the cells by using guanidinium isothiocyanate method. The expression of MCP-1 mRNA in SMCs was detected by using dot blotting analysis using a probe of γ-32p-end-labelled 35-mer oligonucleotide. After a 24-h incubation, the media conditioned by the cultured SMCs were collected. The MCP-1 protein content in the conditioned media was determined by using sandwich ELISA. The results were as follows: Dot blotting analysis showed that the cultured SMCs could express MCP-1 mRNA. After a 4-h exposure to IL-Iβ, TNF-α and LPS, the MCP-1 mRNA expression in SMCs was increased (3.6-fold, 2.3-fold and 1.6-fold, respectively).ELISA showed that the levels of MCP-1 protein in the conditioned media were also increased (2.9-fold, 1.7-fold and 1.1-fold, respectively ). The results suggest that calf aortic SMCs could express MCP-1 mRNA and protein. IL-1β and TNF-α can induce strong expression of MCP- 1mRNA and protein, and the former is more effective than the latter.

  9. Concentrações de IL-6, TNF-α e MCP-1 em crianças com excesso de massa corporal

    Directory of Open Access Journals (Sweden)

    Juliano Magalhães Guedes

    2015-08-01

    Full Text Available O objetivo desta revisão sistemática foi verificar a relação das concentrações de IL-6, TNF-α e MCP-1 em crianças com excesso de massa corporal. As bases de dados investigadas PUBMED, SciELO, LILACS e Periódico Capes foram consultadas retrospectivamente para os últimos seis anos (2009 a 2014 utilizando combinações de palavras chaves como inflamação, IL-6, TNF-α, MCP-1 combinadas com crianças e escolares. Foram analisados 21 artigos. Foi encontrado associação entre sobrepeso/obesidade com IL-6, TNF-α e MCP-1 em 73,3% (11/15, 80% (12/15 e 60% (3/5 dos estudos que analisaram tais marcadores, respectivamente. Crianças com excesso de massa corporal possuem concentrações elevadas de IL-6, TNF-α e MCP-1 resultando em inflamação sistêmica crônica e aumentando o risco de desenvolvimento de outras doenças cardiovasculares. 

  10. Exendin-4 Improves Cardiac Function in Mice Overexpressing Monocyte Chemoattractant Protein-1 in Cardiomyocytes

    OpenAIRE

    Younce, Craig W; Niu, Jianli; Ayala, Jennifer; Burmeister, Melissa A.; Smith, Layton H.; Kolattukudy, Pappachan; Julio E Ayala

    2014-01-01

    The incretin hormone glucagon-like peptide-1 (Glp1) is cardioprotective in models of ischemia-reperfusion injury, myocardial infarction and gluco/lipotoxicity. Inflammation is a factor in these models, yet it is unknown whether Glp1 receptor (Glp1r) agonists are protective against cardiac inflammation. We tested the hypothesis that the Glp1r agonist Exendin-4 (Ex4) is cardioprotective in mice with cardiac-specific monocyte chemoattractant protein-1 overexpression. These MHC-MCP1 mice exhibit ...

  11. Matrine Inhibits Infiltration of the Inflammatory Gr1hi Monocyte Subset in Injured Mouse Liver through Inhibition of Monocyte Chemoattractant Protein-1

    Directory of Open Access Journals (Sweden)

    Duo Shi

    2013-01-01

    Full Text Available Matrine (Mat is a major alkaloid extracted from Sophora flavescens Ait, an herb which is used in the traditional Chinese medicine for treatment of inflammation, cancer, and other diseases. The present study examined the impact of Mat on the CCl4-induced hepatic infiltration of Gr1hi monocytes to explore the possible mechanisms underlying its anti-inflammatory and antifibrotic effects. The results indicated that Mat protected mice from acute liver injury induced by single intraperitoneal injection of CCl4 and attenuated liver fibrosis induced by repeated CCl4 injection. Meanwhile, the infiltrations of Gr1hi monocytes in both acute and chronic injured livers were all inhibited, and the enhanced hepatic expression of MCP-1 was suppressed. Cellular experiments demonstrated that Mat directly inhibited MCP-1 production in both nonparenchymal cells and hepatic stellate cells derived from CCl4-injured livers. Transwell chemotaxis assays showed that Mat significantly inhibited the chemotactic activity of MCP-1. These results suggest that the anti-inflammatory and antifibrotic effects of Mat could be contributed, at least in part, to its prevention of Gr1hi monocyte infiltration into the injured livers and inhibition of MCP-1 production and activity. These findings extend our understanding of the mechanisms underlying the anti-inflammatory and antifibrotic effects of Mat.

  12. Effect of leptin on expression of ICAM-1,LOX-1 and MCP-1 in cultured human umbilical endothelial cell%瘦素对人脐静脉内皮细胞的ICAM-1、LOX-1及MCP-1表达的影响

    Institute of Scientific and Technical Information of China (English)

    崔文章; 赵学忠

    2008-01-01

    目的:探讨瘦素对血管内皮细胞ICAM-1、LOX-1、MCP-1表达的影响,以揭示瘦素致动脉粥样硬化的可能机制.方法:运用逆转录聚合酶链反应测定在不同浓度瘦素作用下,内皮细胞ICAM-1、LOX-1及MCP-ImRNA的表达.结果:空白对照组无瘦索刺激时,ICAM一1、LOX-1及MCP-1的mRNA表达低于瘦素刺激组,加入低剂量瘦素对于ICAM-1、LOX-1及MCP-1的mRNA表达影响不大(P>0.05 ).而随着瘦素剂量的升高,ICAM-1、LOX-1及MCP-1的mRNA表达明显增加,与对照组相比有明显统计学差异(P12 mg/L)可以促进血管内皮细胞ICAM-1、LOX-1及MCP-1的mRNA表达

  13. Jeans type analysis of chemotactic collapse

    CERN Document Server

    Chavanis, Pierre-Henri

    2007-01-01

    We perform a linear dynamical stability analysis of a general hydrodynamic model of chemotactic aggregation [Chavanis & Sire, Physica A, in press (2007)]. Specifically, we study the stability of an infinite and homogeneous distribution of cells against ``chemotactic collapse''. We discuss the analogy between the chemotactic collapse of biological populations and the gravitational collapse (Jeans instability) of self-gravitating systems. Our hydrodynamic model involves a pressure force which can take into account several effects like anomalous diffusion or the fact that the organisms cannot interpenetrate. We also take into account the degradation of the chemical which leads to a shielding of the interaction like for a Yukawa potential. Finally, our hydrodynamic model involves a friction force which quantifies the importance of inertial effects. In the strong friction limit, we obtain a generalized Keller-Segel model similar to the generalized Smoluchowski-Poisson system describing self-gravitating Langevi...

  14. A case-control association study between Obsessive-Compulsive Disorder (OCD and the MCP-1 -2518G/A polymorphism in a Chinese sample Estudo de associação de casos-controle entre Transtorno Obsessivo-Compulsivo (TOC e polimorfismo MCP-1 -2518G/A em uma coorte chinesa

    Directory of Open Access Journals (Sweden)

    Xinhua Zhang

    2012-12-01

    Full Text Available OBJECTIVE: To investigate the association between Obsessive-Compulsive Disorder (OCD and a functional polymorphism of MCP-1 in the Chinese Han population. METHOD: We genotyped and performed a case-control association analysis of the MCP-1 -2518G/A polymorphism in 200 OCD patients and 294 healthy control subjects. RESULTS: There was no significant difference in MCP-1 -2518G/A genotypic and allelic frequencies between OCD cases and controls (x² = 1.123, df = 2, P = 0.57 by genotype; x² = 0.802, df = 1, P = 0.37 by allele. CONCLUSIONS: Our results indicated that MCP-1 -2518G/A may not play a major role in the genetic predisposition of the Chinese Han population to OCD. However, further studies using a larger number of subjects are required to obtain a clear conclusion.OBJETIVO: Investigar a relação entre Transtorno Obsessivo-Compusilvo (TOC e um polimorfismo funcional de MCP-1 na população chinesa de etnia Han. MÉTODOS: Determinamos os genótipos e realizamos uma análise de associações de casos-controle de polimorfismo MCP-1 -2518G/A em 200 indivíduos com TOC e 294 indivíduos saudáveis (controle. RESULTADOS: Não houve diferença significativa no genótipo MCP-1 -2518G/A e nas frequências alélicas entre casos de TOC e controles (x² = 1,123, df = 2, P = 0,57 por genotipo; x² = 0,802, df = 1, P = 0,37 por alelo. CONCLUSÕES: Nossos resultados indicaram que MCP-1 -2518G/A pode não ter grande participação na predisposição genética da etnia Han no que diz respeito ao TOC. Contudo, novos estudos com um maior número de indivíduos são necessários para uma conclusão mais clara.

  15. Recruited alveolar macrophages, in response to airway epithelial-derived monocyte chemoattractant protein 1/CCl2, regulate airway inflammation and remodeling in allergic asthma.

    Science.gov (United States)

    Lee, Yong Gyu; Jeong, Jong Jin; Nyenhuis, Sharmilee; Berdyshev, Evgeny; Chung, Sangwoon; Ranjan, Ravi; Karpurapu, Manjula; Deng, Jing; Qian, Feng; Kelly, Elizabeth A B; Jarjour, Nizar N; Ackerman, Steven J; Natarajan, Viswanathan; Christman, John W; Park, Gye Young

    2015-06-01

    Although alveolar macrophages (AMs) from patients with asthma are known to be functionally different from those of healthy individuals, the mechanism by which this transformation occurs has not been fully elucidated in asthma. The goal of this study was to define the mechanisms that control AM phenotypic and functional transformation in response to acute allergic airway inflammation. The phenotype and functional characteristics of AMs obtained from human subjects with asthma after subsegmental bronchoprovocation with allergen was studied. Using macrophage-depleted mice, the role and trafficking of AM populations was determined using an acute allergic lung inflammation model. We observed that depletion of AMs in a mouse allergic asthma model attenuates Th2-type allergic lung inflammation and its consequent airway remodeling. In both human and mouse, endobronchial challenge with allergen induced a marked increase in monocyte chemotactic proteins (MCPs) in bronchoalveolar fluid, concomitant with the rapid appearance of a monocyte-derived population of AMs. Furthermore, airway allergen challenge of allergic subjects with mild asthma skewed the pattern of AM gene expression toward high levels of the receptor for MCP1 (CCR2/MCP1R) and expression of M2 phenotypic proteins, whereas most proinflammatory genes were highly suppressed. CCL2/MCP-1 gene expression was prominent in bronchial epithelial cells in a mouse allergic asthma model, and in vitro studies indicate that bronchial epithelial cells produced abundant MCP-1 in response to house dust mite allergen. Thus, our study indicates that bronchial allergen challenge induces the recruitment of blood monocytes along a chemotactic gradient generated by allergen-exposed bronchial epithelial cells. PMID:25360868

  16. Platelet-derived growth factor (PDGF-BB-mediated induction of monocyte chemoattractant protein 1 in human astrocytes: implications for HIV-associated neuroinflammation

    Directory of Open Access Journals (Sweden)

    Bethel-Brown Crystal

    2012-12-01

    Full Text Available Abstract Chemokine (C-C motif ligand 2, also known as monocyte chemoattractant protein 1 (MCP-1 is an important factor for the pathogenesis of HIV-associated neurocognitive disorders (HAND. The mechanisms of MCP-1-mediated neuropathogenesis, in part, revolve around its neuroinflammatory role and the recruitment of monocytes into the central nervous system (CNS via the disrupted blood-brain barrier (BBB. We have previously demonstrated that HIV-1/HIV-1 Tat upregulate platelet-derived growth factor (PDGF-BB, a known cerebrovascular permeant; subsequently, the present study was aimed at exploring the regulation of MCP-1 by PDGF-BB in astrocytes with implications in HAND. Specifically, the data herein demonstrate that exposure of human astrocytes to HIV-1 LAI elevated PDGF-B and MCP-1 levels. Furthermore, treating astrocytes with the human recombinant PDGF-BB protein significantly increased the production and release of MCP-1 at both the RNA and protein levels. MCP-1 induction was regulated by activation of extracellular-signal-regulated kinase (ERK1/2, c-Jun N-terminal kinase (JNK and p38 mitogen-activated protein (MAP kinases and phosphatidylinositol 3-kinase (PI3K/Akt pathways and the downstream transcription factor, nuclear factor κB (NFκB. Chromatin immunoprecipitation (ChIP assays demonstrated increased binding of NFκB to the human MCP-1 promoter following PDGF-BB exposure. Conditioned media from PDGF-BB-treated astrocytes increased monocyte transmigration through human brain microvascular endothelial cells (HBMECs, an effect that was blocked by STI-571, a tyrosine kinase inhibitor (PDGF receptor (PDGF-R blocker. PDGF-BB-mediated release of MCP-1 was critical for increased permeability in an in vitro BBB model as evidenced by blocking antibody assays. Since MCP-1 is linked to disease severity, understanding its modulation by PDGF-BB could aid in understanding the proinflammatory responses in HAND. These results suggest that astrocyte

  17. Effect of ARB on Expression of CD68 and MCP-1 in Adipose Tissue of Rats on Long-term High Fat Diet

    Institute of Scientific and Technical Information of China (English)

    Caihong GUO; Li YUAN; Xiaoling LIU; Aimin DU; Yan HUANG; Lili ZHANG

    2008-01-01

    In adipose tissue of rats on long-term high fat diet, the inflammatory changes the roles of angiotensin receptor blocker (ARB) in pimelitis and insulin resistance (IR) were observed. IR rat model was established by feeding high calorie and high fat diet. The change in insulin sensitivity was detected by euglycemic-hyperinsulinemic clamp technique 8 weeks after intervention by valsartan. The expression levels of CD68 and MCP-1 mRNA and proteins in adipose tissue were examined by RT-PCR and immunohistochemistry respectively. The parameters of blood glucose, insulin and blood lipid were analyzed. The results showed that in high fat diet group intra-abdominal obesity developed, the content of visceral fat and the number of inflammatory cells in local adipose tissue were significantly increased (p<0.01), the levels of serum triglyceride, free fatty acids and fasting serum insulin were markedly increased, the insulin sensitivity was significantly lowered (p<0.01), and the expression of CD68 and MCP-1 was significantly increased as compared with control group (P<0.01). In ARB interventional group, the content of visceral fat, the number of inflammatory cells and the expression of CD68 and MCP-1 in local adipose tissue were significantly reduced (all P<0.01), but the insulin sensitivity was significantly enhanced (P<0.01) as compared with high fat diet group. There were pimelitis and IR in rats with obesity induced by long-term high calorie and high fat diet. The ARB can significantly inhibit the infiltration of macrophages and the expression of MCP-1 in adipose tissue, thereby attenuating the inflammation and improving IR in rats.

  18. Ox-LDL Promotes Migration and Adhesion of Bone Marrow-Derived Mesenchymal Stem Cells via Regulation of MCP-1 Expression

    Directory of Open Access Journals (Sweden)

    Fenxi Zhang

    2013-01-01

    Full Text Available Bone marrow-derived mesenchymal stem cells (bmMSCs are the most important cell source for stem cell transplant therapy. The migration capacity of MSCs is one of the determinants of the efficiency of MSC-based transplant therapy. Our recent study has shown that low concentrations of oxidized low-density lipoprotein (ox-LDL can stimulate proliferation of bmMSCs. In this study, we investigated the effects of ox-LDL on bmMSC migration and adhesion, as well as the related mechanisms. Our results show that transmigration rates of bmMSCs and cell-cell adhesion between bmMSCs and monocytes are significantly increased by treatments with ox-LDL in a dose- and time-dependent manner. Expressions of ICAM-1, PECAM-1, and VCAM-1 as well as the levels of intracellular Ca2+ are also markedly increased by ox-LDL in a dose-dependent manner. Cytoskeleton analysis shows that ox-LDL treatment benefits to spreading of bmMSCs and organization of F-actin fibers after being plated for 6 hours. More interestingly, treatments with ox-LDL also markedly increase expressions of LOX-1, MCP-1, and TGF-β; however, LOX-1 antibody and MCP-1 shRNA markedly inhibit ox-LDL-induced migration and adhesion of bmMSCs, which suggests that ox-LDL-induced bmMSC migration and adhesion are dependent on LOX-1 activation and MCP-1 expression.

  19. Nicotine is Chemotactic for Neutrophils and Enhances Neutrophil Responsiveness to Chemotactic Peptides

    Science.gov (United States)

    Totti, Noel; McCusker, Kevin T.; Campbell, Edward J.; Griffin, Gail L.; Senior, Robert M.

    1984-01-01

    Neutrophils contribute to chronic bronchitis and pulmonary emphysema associated with cigarette smoking. Nicotine was found to be chemotactic for human neutrophils but not monocytes, with a peak activity at ~ 31 micromolar. In lower concentrations (comparable to those in smokers' plasma), nicotine enhanced the response of neutrophils to two chemotactic peptides. In contrast to most other chemoattractants for neutrophils, however, nicotine did not affect degranulation or superoxide production. Nicotine thus may promote inflammation and consequent lung injury in smokers.

  20. Induction of mitochondrial uncoupling enhances VEGF₁₂₀ but reduces MCP-1 release in mature 3T3-L1 adipocytes: possible regulatory mechanism through endogenous ER stress and AMPK-related pathways.

    Science.gov (United States)

    Miyokawa-Gorin, Kaoru; Takahashi, Kazuto; Handa, Keiko; Kitahara, Atsuko; Sumitani, Yoshikazu; Katsuta, Hidenori; Tanaka, Toshiaki; Nishida, Susumu; Yoshimoto, Katsuhiko; Ohno, Hideki; Ishida, Hitoshi

    2012-03-01

    Although white adipocytes contain a larger number of mitochondria per cytoplasmic volume, adipocyte mitochondrial uncoupling to reduce the efficiency of ATP production on cellular function including secretory regulation of bioactive molecules such as VEGF and MCP-1 remains to be elucidated. Here we induce mitochondrial uncoupling under hypoxia-independent conditions in mature 3T3-L1 adipocytes using a metabolic uncoupler, dinitrophenol (DNP). MCP-1 release was significantly decreased by 26% (poxidative stress was observed. Treatment with thapsigargin, which can induce exogenous endoplasmic reticulum (ER) stress, clearly attenuated MCP-1 release (pmetabolic syndrome and type 2 diabetes.

  1. Suppression of lipin-1 expression increases monocyte chemoattractant protein-1 expression in 3T3-L1 adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Nobuhiko, E-mail: ntkhs@hoku-iryo-u.ac.jp [Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510 (Japan); Yoshizaki, Takayuki [Innovation Center, Kagoshima University, 1-21-40 Korimoto, Kagoshima 890-0065 (Japan); Hiranaka, Natsumi; Suzuki, Takeshi [Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Yui, Tomoo; Akanuma, Masayasu; Oka, Kazuya [Department of Fixed Prosthodontics and Oral Implantology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Kanazawa, Kaoru [Department of Dental Anesthesiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Yoshida, Mika; Naito, Sumiyoshi [Department of Clinical Laboratory, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Fujiya, Mikihiro; Kohgo, Yutaka [Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510 (Japan); Ieko, Masahiro [Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan)

    2011-11-11

    Highlights: Black-Right-Pointing-Pointer Lipin-1 affects lipid metabolism, adipocyte differentiation, and transcription. Black-Right-Pointing-Pointer Adipose lipin-1 expression is reduced in obesity. Black-Right-Pointing-Pointer Lipin-1 depletion using siRNA in 3T3-L1 adipocytes increased MCP-1 expression. Black-Right-Pointing-Pointer Lipin-1 is involved in adipose inflammation. -- Abstract: Lipin-1 plays a crucial role in the regulation of lipid metabolism and cell differentiation in adipocytes. Expression of adipose lipin-1 is reduced in obesity, and metabolic syndrome. However, the significance of this reduction remains unclear. This study investigated if and how reduced lipin-1 expression affected metabolism. We assessed mRNA expression levels of various genes related to adipocyte metabolism in lipin-1-depleted 3T3-L1 adipocytes by introducing its specific small interfering RNA. In lipin-1-depleted adipocytes, mRNA and protein expression levels of monocyte chemoattractant protein-1 (MCP-1) were significantly increased, although the other genes tested were not altered. The conditioned media from the cells promoted monocyte chemotaxis. The increase in MCP-1 expression was prevented by treatment with quinazoline or salicylate, inhibitors of nuclear factor-{kappa}B activation. Because MCP-1 is related to adipose inflammation and systemic insulin resistance, these results suggest that a reduction in adipose lipin-1 in obesity may exacerbate adipose inflammation and metabolism.

  2. Suppression of lipin-1 expression increases monocyte chemoattractant protein-1 expression in 3T3-L1 adipocytes

    International Nuclear Information System (INIS)

    Highlights: ► Lipin-1 affects lipid metabolism, adipocyte differentiation, and transcription. ► Adipose lipin-1 expression is reduced in obesity. ► Lipin-1 depletion using siRNA in 3T3-L1 adipocytes increased MCP-1 expression. ► Lipin-1 is involved in adipose inflammation. -- Abstract: Lipin-1 plays a crucial role in the regulation of lipid metabolism and cell differentiation in adipocytes. Expression of adipose lipin-1 is reduced in obesity, and metabolic syndrome. However, the significance of this reduction remains unclear. This study investigated if and how reduced lipin-1 expression affected metabolism. We assessed mRNA expression levels of various genes related to adipocyte metabolism in lipin-1-depleted 3T3-L1 adipocytes by introducing its specific small interfering RNA. In lipin-1-depleted adipocytes, mRNA and protein expression levels of monocyte chemoattractant protein-1 (MCP-1) were significantly increased, although the other genes tested were not altered. The conditioned media from the cells promoted monocyte chemotaxis. The increase in MCP-1 expression was prevented by treatment with quinazoline or salicylate, inhibitors of nuclear factor-κB activation. Because MCP-1 is related to adipose inflammation and systemic insulin resistance, these results suggest that a reduction in adipose lipin-1 in obesity may exacerbate adipose inflammation and metabolism.

  3. Kinetic and hydrodynamic models of chemotactic aggregation

    CERN Document Server

    Chavanis, Pierre-Henri

    2007-01-01

    We derive general kinetic and hydrodynamic models of chemotactic aggregation that describe certain features of the morphogenesis of biological colonies (like bacteria, amoebae, endothelial cells or social insects). Starting from a stochastic model defined in terms of N coupled Langevin equations, we derive a nonlinear mean field Fokker-Planck equation governing the evolution of the distribution function of the system in phase space. By taking the successive moments of this kinetic equation and using a local thermodynamic equilibrium condition, we derive a set of hydrodynamic equations involving a damping term. In the limit of small frictions, we obtain a hyperbolic model describing the formation of network patterns (filaments) and in the limit of strong frictions we obtain a parabolic model which is a generalization of the standard Keller-Segel model describing the formation of clusters (clumps). Our approach connects and generalizes several models introduced in the chemotactic literature. We discuss the anal...

  4. Jeans type analysis of chemotactic collapse

    Science.gov (United States)

    Chavanis, Pierre-Henri; Sire, Clément

    2008-07-01

    We perform a linear dynamical stability analysis of a general hydrodynamic model of chemotactic aggregation [P.H. Chavanis, C. Sire, Physica A 384 (2007) 199]. Specifically, we study the stability of an infinite and homogeneous distribution of cells against “chemotactic collapse”. We discuss the analogy between the chemotactic collapse of biological populations and the gravitational collapse (Jeans instability) of self-gravitating systems. Our hydrodynamic model involves a pressure force which can take into account several effects like anomalous diffusion or the fact that the organisms cannot interpenetrate. We also take into account the degradation of the chemical which leads to a shielding of the interaction like for a Yukawa potential. Finally, our hydrodynamic model involves a friction force which quantifies the importance of inertial effects. In the strong friction limit, we obtain a generalized Keller-Segel model similar to the generalized Smoluchowski-Poisson system describing self-gravitating Langevin particles. For small frictions, we obtain a hydrodynamic model of chemotaxis similar to the Euler-Poisson system describing a self-gravitating barotropic gas. We show that an infinite and homogeneous distribution of cells is unstable against chemotactic collapse when the “velocity of sound” in the medium is smaller than a critical value. We study in detail the linear development of the instability and determine the range of unstable wavelengths, the growth rate of unstable modes and the damping rate, or the pulsation frequency, of the stable modes as a function of the friction parameter and shielding length. For specific equations of state, we express the stability criterion in terms of cell density.

  5. Gradient sensing in defined chemotactic fields

    OpenAIRE

    Skoge, Monica; Adler, Micha; Groisman, Alex; Levine, Herbert; Loomis, William F.; Rappel, Wouter-Jan

    2010-01-01

    Cells respond to a variety of secreted molecules by modifying their physiology, growth patterns, and behavior. Motile bacteria and eukaryotic cells can sense extracellular chemoattractants and chemorepellents and alter their movement. In this way fibroblasts and leukocytes can find their ways to sites of injury and cancer cells can home in on sites that are releasing growth factors. Social amoebae such as Dictyostelium are chemotactic to cAMP which they secrete several hours after they have i...

  6. Chronic photo-oxidative stress and subsequent MCP-1 activation as causative factors for age-related macular degeneration.

    Science.gov (United States)

    Suzuki, Mihoko; Tsujikawa, Motokazu; Itabe, Hiroyuki; Du, Zhao-Jiang; Xie, Ping; Matsumura, Nagakazu; Fu, Xiaoming; Zhang, Renliang; Sonoda, Koh-hei; Egashira, Kensuke; Hazen, Stanley L; Kamei, Motohiro

    2012-05-15

    Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. Although pathogenic factors, such as oxidative stress, inflammation and genetics are thought to contribute to the development of AMD, little is known about the relationships and priorities between these factors. Here, we show that chronic photo-oxidative stress is an environmental factor involved in AMD pathogenesis. We first demonstrated that exposure to light induced phospholipid oxidation in the mouse retina, which was more prominent in aged animals. The induced oxidized phospholipids led to an increase in the expression of monocyte chemoattractant protein-1, which then resulted in macrophage accumulation, an inflammatory process. Antioxidant treatment prevented light-induced phospholipid oxidation and the subsequent increase of monocyte chemoattractant protein-1 (also known as C-C motif chemokine 2; CCL2), which are the beginnings of the light-induced changes. Subretinal application of oxidized phospholipids induced choroidal neovascularization, a characteristic feature of wet-type AMD, which was inhibited by blocking monocyte chemoattractant protein-1. These findings strongly suggest that a sequential cascade from photic stress to inflammatory processes through phospholipid oxidation has an important role in AMD pathogenesis. Finally, we succeeded in mimicking human AMD in mice with low-level, long-term photic stress, in which characteristic pathological changes, including choroidal neovascularization formation, were observed. Therefore, we propose a consecutive pathogenic pathway involving photic stress, oxidation of phospholipids and chronic inflammation, leading to angiogenesis. These findings add to the current understanding of AMD pathology and suggest protection from oxidative stress or suppression of the subsequent inflammation as new potential therapeutic targets for AMD. PMID:22357958

  7. Monocyte chemotactic protein-1 and other inflammatory parameters in Bernese Mountain dogs with disseminated histiocytic sarcoma

    DEFF Research Database (Denmark)

    Nielsen, Lise Nikolic; Kjelgaard-Hansen, Mads; Kristensen, Annemarie Thuri

    2013-01-01

    The interaction between cancer and the immune system, and the production of cytokines by the tumour itself have been associated with altered levels of cytokines in human cancer patients. Bernese Mountain dogs with disseminated histiocytic sarcoma (DHS) show vague and non-specific clinical signs....... Although histiocytes can secrete cytokines in response to inflammatory stimuli, serum cytokine concentrations in dogs with DHS have not previously been investigated. The aim of this study was to evaluate the immunological state of untreated Bernese Mountain dogs with DHS by assessing multiple serum...... cytokines and to correlate these with other inflammatory markers. As a prospective case control study, 17 Bernese Mountain dogs with DHS were included along with 18 healthy controls (12 Bernese Mountain dogs and 6 dogs of various breeds). Blood samples were examined for fibrinogen, C-reactive protein (CRP...

  8. CHANGE AND CLINICAL SIGNIFICANCE OF IL-16, IL-35, MCP-1 LEVELS OF BRONCHIAL ASTHMA CHILDREN WITH ACUTE EPISODES%支气管哮喘儿童血清IL-16、IL-35、MCP-1的水平变化及临床意义

    Institute of Scientific and Technical Information of China (English)

    林志波; 黄海忠

    2015-01-01

    目的 探讨支气管哮喘儿童血清中IL-16、IL-35、单核细胞趋化蛋白-1(MCP-1)的水平变化及临床意义.方法 选择2012年1月至2014年6月60例哮喘急性发作期患儿为研究对象.选择36例哮喘缓解期患儿为疾病对照组.选择2012年1月至2014年6月期间健康儿童40例为健康对照组.统计受试者血清IL-16、IL-35、MCP-1水平,并对血清IL-16、IL-35、MCP-1水平与年龄、病程、性别、哮喘严重程度、病情进行相关性分析.结果 哮喘急性发作期血清IL-16、MCP-1水平均高于哮喘缓解期、健康对照组(p<0.01);缓解期患儿血清IL-16、MCP-1水平高于健康对照组(p<0.01);哮喘急性发作期血清IL-35水平均低于哮喘缓解期、健康对照组(p<0.01);缓解期患儿血清IL-35水平低于健康对照组(p<0.01);哮喘中重度组血清IL-16、MCP-1水平均高于轻度组、对照组(p<0.01);轻度组患儿血清IL-16、MCP-1水平高于对照组(p<0.01);哮喘中重度组血清IL-35水平均低于轻度组、对照组(p<0.01);轻度组患儿血清IL-35水平低于对照组(p<0.01);治疗后哮喘急性发作期患儿血清IL-16、MCP-1水平低于治疗前(p<0.001),治疗后哮喘急性发作期患儿血清IL-35水平高于治疗前(p<0.001);血清IL-16、MCP-1水平与哮喘严重程度、病情呈正相关(p<0.05);血清IL-35水平与哮喘严重程度、病情呈负相关(p<0.05).血清IL-16水平与血清MCP-1水平呈正相关(p<0.05),与血清IL-35水平呈负相关(p<0.05),血清MCP-1水平与血清IL-35水平呈负相关(p<0.05).结论 IL-16、MCP-1在哮喘患儿血中高表达,IL-35在哮喘患儿血中低表达;IL-16、IL-35、MCP-1与哮喘发病及进展密切相关.

  9. Febuxostat, an inhibitor of xanthine oxidase, suppresses lipopolysaccharide-induced MCP-1 production via MAPK phosphatase-1-mediated inactivation of JNK.

    Directory of Open Access Journals (Sweden)

    Johji Nomura

    Full Text Available Excess reactive oxygen species (ROS formation can trigger various pathological conditions such as inflammation, in which xanthine oxidase (XO is one major enzymatic source of ROS. Although XO has been reported to play essential roles in inflammatory conditions, the molecular mechanisms underlying the involvement of XO in inflammatory pathways remain unclear. Febuxostat, a selective and potent inhibitor of XO, effectively inhibits not only the generation of uric acid but also the formation of ROS. In this study, therefore, we examined the effects of febuxostat on lipopolysaccharide (LPS-mediated inflammatory responses. Here we show that febuxostat suppresses LPS-induced MCP-1 production and mRNA expression via activating MAPK phosphatase-1 (MKP-1 which, in turn, leads to dephosphorylation and inactivation of JNK in macrophages. Moreover, these effects of febuxostat are mediated by inhibiting XO-mediated intracellular ROS production. Taken together, our data suggest that XO mediates LPS-induced phosphorylation of JNK through ROS production and MKP-1 inactivation, leading to MCP-1 production in macrophages. These studies may bring new insights into the novel role of XO in regulating inflammatory process through MAPK phosphatase, and demonstrate the potential use of XO inhibitor in modulating the inflammatory processes.

  10. Monocyte chemoattractant protein-1: a proinflammatory cytokine elevated in sarcopenic obesity

    Directory of Open Access Journals (Sweden)

    Lim JP

    2015-03-01

    Full Text Available Jun Pei Lim,1,2 Bernard P Leung,3 Yew Yoong Ding,1,2 Laura Tay,1,2 Noor Hafizah Ismail,2,4 Audrey Yeo,2 Suzanne Yew,2 Mei Sian Chong1,2 1Department of Geriatric Medicine, 2Institute of Geriatrics and Active Ageing, 3Department of Rheumatology, Allergy and Immunology, 4Department of Community and Continuing Care, Tan Tock Seng Hospital, Singapore Objective: Sarcopenic obesity (SO is associated with poorer physical outcomes and functional status in the older adult. A proinflammatory milieu associated with central obesity is postulated to enhance muscle catabolism. We set out to examine associations of the chemokine monocyte chemoattractant protein-1 (MCP-1 in groups of older adults, with sarcopenia, obesity, and the SO phenotypes.Methods: A total of 143 community dwelling, well, older adults were recruited. Cross-sectional clinical data, physical performance, and muscle mass measurements were collected. Obesity and sarcopenia were defined using revised National Cholesterol Education Program (NCEP obesity guidelines and those of the Asian Working Group for Sarcopenia. Serum levels of MCP-1 were measured by enzyme-linked immunosorbent assay (ELISA.Results: In all, 25.2% of subjects were normal, 15.4% sarcopenic, 48.3% obese, and 11.2% were SO. The SO groups had the lowest appendicular lean mass, highest percentage body fat, and lowest performance scores on the Short Physical Performance Battery and grip strength. The MCP-1 levels were significantly different, with the highest levels found in SO participants (P<0.05.Conclusion: Significantly raised MCP-1 levels in obese and SO subjects support the theory of chronic inflammation due to excess adiposity. Longitudinal studies will reveal whether SO represents a continuum of obesity causing accelerated sarcopenia and cardiovascular events, or the coexistence of two separate conditions with synergistic effects affecting functional performance. Keywords: chemokine C-C motif ligand 2 (CCL-2, elderly

  11. Identification of a chemotactic sensitivity in a coupled system

    CERN Document Server

    Fister, K Renee

    2007-01-01

    Chemotaxis is the process by which cells behave in a way that follows the chemical gradient. Applications to bacteria growth, tissue inflammation, and vascular tumors provide a focus on optimization strategies. Experiments can characterize the form of possible chemotactic sensitivities. This paper addresses the recovery of the chemotactic sensitivity from these experiments while allowing for nonlinear dependence of the parameter on the state variables. The existence of solutions to the forward problem is analyzed. The identification of a chemotactic parameter is determined by inverse problem techniques. Tikhonov regularization is investigated and appropriate convergence results are obtained. Numerical results of concentration dependent chemotactic terms are explored.

  12. Advanced oxidation protein products induce monocyte chemoattractant protein-1 expression via p38 mitogen-activated protein kinase activation in rat vascular smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    PENG Kan-fu; WU Xiong-fei; ZHAO Hong-wen; SUN Yan

    2006-01-01

    Background Advanced oxidation protein products (AOPPs) are new uremic toxins reported by Witko-Sarsat in 1996, which are associated with the pathogenesis of atherosclerosis. However, the mechanisms by which AOPPs enhance atherosclerosis have not been fully understood. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine which stimulates migration of monocytes and plays a critical role in the development of atherosclerosis. In this study, we investigated the effect of AOPPs on MCP-1 expression in cultured vascular smooth muscle cells (VSMCs).Methods VSMCs were cultured and then co-incubated with AOPP (200 μ mol/L, 400 μ mol/L) for different times with or without pretreatment with specific p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580. RT-PCR and Western blott were used to detect MCP-1 mRNA and protein expression at different time points after AOPP stimulation in rat smooth muscle cells. Western blot was used to detect the expression of phosphorylated p38 MAPK.Results Treatment of VSMC with AOPPs resulted in a significant increase of the expression of MCP- 1 mRNA and protein in time- and dose-dependent manner, and could activated p38 MAPK. Pretreatment of VSMCs with SB203580 resulted in a dose-dependent inhibition of AOPPs-induced MCP-1 mRNA and protein expression.Conclusions AOPPs can stimulate MCP-1 expression via p38 MAPK in VSMCs. This suggests that AOPPs might contribute to the formation of atherosclerosis through this proinflammatory effect.

  13. Monocyte chemoattractant protein-1 secreted by decidual stromal cells inhibits NK cells cytotoxicity by up-regulating expression of SOCS3.

    Directory of Open Access Journals (Sweden)

    Xiaofei Xu

    Full Text Available BACKGROUND: Decidual stromal cells (DSCs are of particular importance due to their pleiotropic functions during pregnancy. Although previous research has demonstrated that DSCs participated in the regulation of immune cells during pregnancy, the crosstalk between DSCs and NK cells has not been fully elucidated. To address this issue, we investigated the effect of DSCs on perforin expression in CD56(+ NK cells and explored the underlying mechanism. METHODOLOGY/PRINCIPAL FINDINGS: Flow cytometry analysis showed perforin production in NK cells was attenuated by DSC media, and it was further suppressed by media from DSCs pretreated with lipopolysaccharide (LPS. However, the expression of granzyme A and apoptosis of NK cells were not influenced by DSC media. ELISA assays to detect cytokine production indicated that monocyte chemoattractant protein-1 (MCP-1 in the supernatant of DSCs conditioned culture significantly increased after LPS stimulation. The inhibitory effect of DSC media on perforin was abolished by the administration of anti-MCP-1 neutralizing antibody. Notably, reduced perforin expression attenuated the cytotoxic potential of CD56(+ NK cells to K562 cells. Moreover, Suppressor of cytokine signaling 3 (SOCS3 expression in NK cells was enhanced by treatment with MCP-1, as measured by RT-PCR and western blot. Interestingly, MCP-1-induced perforin expression was partly abolished by the siRNA induced SOCS3 knockdown. Western blot analysis suggested that both NF-κB and ERK/MAPKs pathway were involved in the LPS-induced upregulation of MCP-1 in DSCs. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that LPS induces upregulation of MCP-1 in DSCs, which may play a critical role in inhibiting the cytotoxicity of NK cells partly by promoting SOCS3 expression. These findings suggest that the crosstalk between DSCs and NK cells may be crucial to maintain pregnancy homeostasis.

  14. Isoprenaline increases serum levels of monocyte chemoattractant protein-1 and tissue inhibitor of matrix metalloproteinases type Ⅰ in Wistar rats

    Institute of Scientific and Technical Information of China (English)

    LEI He-ping; ZHANG Meng-zhen; YANG Xiang-yu; HOU Xing-hua; LIN Qiu-xiong; YANG Min; ZHONG Shi-long

    2016-01-01

    Background Treatment of rats with the beta-adrenergic agonist Isoprenaline (ISO) results in cardiac hypertrophy and myocardial fibrosis.In the present work,we aimed to study the in vivo effects of ISO on serum levels of monocyte chemoattractant protein-1 and tissue inhibitor of matrix metalloproteinases type Ⅰ in Wistar rats.Methods ISO (5 mg· kg-1) or Saline were injected subcutaneously into Wistar rats once a day for 3 or 7 consecutive days.Ventricular remodeling and cardiac function were evaluated by echocardiography.Sections of heart were stained with hematoxylin-eosin (HE) for histopathology or with Masson's trichrome for collagen visualization.In addition,heart tissue immunohistochemistry for α-SMA was also analyzed.The serum levels of tissue inhibitor of matrix metalloproteinases type Ⅰ (TIMP-1) and monocyte chemoattractant protein-1 (MCP-1) were determined by Luminex multiplex technology.Results ISO induced cardiac dysfunction in rats after 3 or 7 days of treatment.ISO caused significant increase of myocardial disorder and fibrosis withincreased α-SMA expression.ISO treated aats showed a significant increase in the serum levels of TIMP-1 and MCP-1.Conclusions Our study suggests that ISO induces profound cardiac remodeling accompanied with increase of serum TIMP-1 and MCP-1.

  15. Monocyte chemoattractant protein-1 plays a key role in type 1 diabetes

    Institute of Scientific and Technical Information of China (English)

    Dong Li; Guoliang Liu

    2005-01-01

    Type 1 diabetes is an autoimmune disease resulting from the selective destruction of β cells in the pancreatic islets.In both human and rodent models of type 1 diabetes, the clinical disease is preceded by a progressive mononuclear cell invasion of the pancreatic islets (insulitis). In the early stage of insulitis, the major components are monocyte/macrophages, and the recruitment of mononuclear cells is a critical step in the pathogenesis of the type 1 diabetes. Studies have revealed that Monocyte chemoattractant protein-1(MCP-1)specifically recruits monocytes/macrophages into pancreas and plays an important role in the development of insulitis and diabetes.

  16. Insulin Resistance, Inflammation, and Obesity: Role of Monocyte Chemoattractant Protein-1 (orCCL2 in the Regulation of Metabolism

    Directory of Open Access Journals (Sweden)

    Anna Rull

    2010-01-01

    Full Text Available To maintain homeostasis under diverse metabolic conditions, it is necessary to coordinate nutrient-sensing pathways with the immune response. This coordination requires a complex relationship between cells, hormones, and cytokines in which inflammatory and metabolic pathways are convergent at multiple levels. Recruitment of macrophages to metabolically compromised tissue is a primary event in which chemokines play a crucial role. However, chemokines may also transmit cell signals that generate multiple responses, most unrelated to chemotaxis, that are involved in different biological processes. We have reviewed the evidence showing that monocyte chemoattractant protein-1 (MCP-1 or CCL2 may have a systemic role in the regulation of metabolism that sometimes is not necessarily linked to the traffic of inflammatory cells to susceptible tissues. Main topics cover the relationship between MCP-1/CCL2, insulin resistance, inflammation, obesity, and related metabolic disturbances.

  17. Dynamics of Chemotactic Droplets in Salt Concentration Gradients

    DEFF Research Database (Denmark)

    Cejkova, J.; Novak, M.; Stepanek, F.;

    2014-01-01

    The chemotactic movement of decanol droplets in aqueous solutions of sodium decanoate in response to concentration gradients of NaCl has been investigated. Key parameters of the chemotactic response, namely the induction time and the migration velocity, have been evaluated as a function of the so...

  18. Maternal immune activation by poly(I:C induces expression of cytokines IL-1β and IL-13, chemokine MCP-1 and colony stimulating factor VEGF in fetal mouse brain

    Directory of Open Access Journals (Sweden)

    Arrode-Brusés Géraldine

    2012-04-01

    Full Text Available Abstract Background Maternal viral infection during pregnancy is associated with an increase in the incidence of psychiatric disorders with presumed neurodevelopmental origin, including autism spectrum disorders and schizophrenia. The enhanced risk for developing mental illness appears to be caused by deleterious effects of innate immune response-associated factors on the development of the central nervous system, which predispose the offspring to pathological behaviors in adolescence and adulthood. To identify the immune response-associated soluble factors that may affect central nervous system development, we examined the effect of innate immune response activation by polyriboinosinic-polyribocytidylic acid (poly(I:C, a synthetic analogue of viral double-stranded RNA, on the expression levels of pro- and anti-inflammatory cytokines, chemokines and colony stimulating factors in fetal and postnatal mouse brain 6 h and 24 h after treatment. Methods C57BL/6J pregnant mice (gestational day 16 or newborn mice (postnatal day 4 received a single intraperitoneal injection of the synthetic analogue of viral double-stranded RNA poly(I:C (20 mg/kg. Thirty-two immune response-associated soluble factors, including pro- and anti-inflammatory cytokines, chemokines and colony stimulating factors, were assayed 6 h and 24 h after poly(I:C injection using multiplexed bead-based immunoassay (Milliplex Map and processed in a Luminex 100 IS instrument. Results Maternal exposure to poly(I:C at gestational day 16 induced a significant increase in cytokines interleukin (IL-1β, IL-7 and IL-13; chemokines monocyte chemoattractant protein 1 (MCP-1, macrophage inflammatory protein (MIP-1α, interferon gamma-induced protein (IP-10 and monokine induced by IFN-gamma (MIG; and in the colony stimulating factor vascular endothelial growth factor (VEGF in the fetal brain. IL-1β showed the highest concentration levels in fetal brains and was the only cytokine

  19. Chemotactic selection of pollutant degrading soil bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Hazen, T.C.

    1991-03-04

    A method is described for identifying soil microbial strains which may be bacterial degraders of pollutants. This method includes: Placing a concentration of a pollutant in a substantially closed container; placing the container in a sample of soil for a period of time ranging from one minute to several hours; retrieving the container and collecting its contents; microscopically determining the identity of the bacteria present. Different concentrations of the pollutant can be used to determine which bacteria respond to each concentration. The method can be used for characterizing a polluted site or for looking for naturally occurring biological degraders of the pollutant. Then bacteria identified as degraders of the pollutant and as chemotactically attracted to the pollutant are used to innoculate contaminated soil. To enhance the effect of the bacteria on the pollutant, nutrients are cyclicly provided to the bacteria then withheld to alternately build up the size of the bacterial colony or community and then allow it to degrade the pollutant.

  20. Urinary monocyte chemoattractant protein-1 and hepcidin and early diabetic nephropathy lesions in type 1 diabetes mellitus

    Science.gov (United States)

    Fufaa, Gudeta D.; Weil, E. Jennifer; Nelson, Robert G.; Hanson, Robert L.; Knowler, William C.; Rovin, Brad H.; Wu, Haifeng; Klein, Jon B.; Mifflin, Theodore E.; Feldman, Harold I.; Vasan, Ramachandran S.; Kimmel, Paul L.; Kusek, John W.; Mauer, Michael; Zinman, Bernard; Donnelly, Sandra; Canada, Toronto; Gardiner, Robert; Suissa, Samy; Drummond, Keith; Goodyer, Paul; Sinaiko, Alan; Strand, Trudy; Gubler, Marie Claire; Klein, Ronald

    2015-01-01

    Background Urinary monocyte chemoattractant protein-1 (MCP-1) and hepcidin are potential biomarkers of renal inflammation. We examined their association with development of diabetic nephropathy (DN) lesions in normotensive normoalbuminuric subjects with type 1 diabetes (T1D) from the Renin-Angiotensin System Study. Methods Biomarker concentrations were measured in baseline urine samples from 224 subjects who underwent kidney biopsies at baseline and after 5 years. Fifty-eight urine samples below the limit of quantitation (LOQ, 28.8 pg/mL) of the MCP-1 assay were assigned concentrations of LOQ/√2 for analysis. Relationships between ln(MCP-1/Cr) or ln(hepcidin/Cr) and morphometric variables were assessed by sex using multiple linear regression after adjustment for age, T1D duration, HbA1c, mean arterial pressure, albumin excretion rate (AER) and glomerular filtration rate (GFR). In models that examined changes in morphometric variables, the baseline morphometric value was also included. Results Baseline mean age was 24.6 years, mean duration of T1D 11.2 years, median AER 6.4 µg/min and mean iohexol GFR 129 mL/min/1.73 m2. No associations were found between hepcidin/Cr and morphometric variables. Higher MCP-1/Cr was associated with higher interstitial fractional volume at baseline and after 5 years in women (baseline partial r = 0.244, P = 0.024; 5-year partial r = 0.299, P = 0.005), but not in men (baseline partial r = −0.049, P = 0.678; 5-year partial r = 0.026, P = 0.830). MCP-1 was not associated with glomerular lesions in either sex. Conclusions Elevated urinary MCP-1 concentration measured before clinical findings of DN in women with T1D was associated with changes in kidney interstitial volume, suggesting that inflammatory processes may be involved in the pathogenesis of early interstitial changes in DN. PMID:25648911

  1. Gradient sensing in defined chemotactic fields.

    Science.gov (United States)

    Skoge, Monica; Adler, Micha; Groisman, Alex; Levine, Herbert; Loomis, William F; Rappel, Wouter-Jan

    2010-11-01

    Cells respond to a variety of secreted molecules by modifying their physiology, growth patterns, and behavior. Motile bacteria and eukaryotic cells can sense extracellular chemoattractants and chemorepellents and alter their movement. In this way fibroblasts and leukocytes can find their way to sites of injury and cancer cells can home in on sites that are releasing growth factors. Social amoebae such as Dictyostelium are chemotactic to cAMP which they secrete several hours after they have initiated development. These eukaryotic cells are known to be able to sense extremely shallow gradients but the processes underlying their exquisite sensitivity are still largely unknown. In this study we determine the responses of developed cells of Dictyostelium discoideum to stable linear gradients of cAMP of varying steepness generated in 2 μm deep gradient chambers of microfluidic devices. The gradients are generated by molecular diffusion between two 80 μm deep flow-through channels, one of which is perfused with a solution of cAMP and the other with buffer, serving as continuously replenished source and sink. These low ceiling gradient chambers constrained the cells in the vertical dimension, facilitating confocal imaging, such that subcellular localization of fluorescently tagged proteins could be followed for up to 30 min without noticeable phototoxicity. Chemotactic cells enter these low ceiling chambers by flattening and elongating and then move almost as rapidly as unconstrained cells. By following the localization of activated Ras (RasGTP) using a Ras Binding Domain fused to Green Fluorescent Protein (RBD-GFP), we observed the rapid appearance of membrane associated patches at the tips of pseudopods. These patches remained associated with pseudopods while they continued to extend but were rapidly disassembled when pseudopods stalled and the cell moved past them. Likewise, fluorescence associated with localized RasGTP rapidly disappeared when the gradient was turned

  2. Effects of Simvastatin on NF-κB-DNA Binding Activity and Monocyte Chemoattractant Protein-1 Expression in a Rabbit Model of Atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    YANG Xiaoyun; WANG Lin; ZENG Hesong; DUBEY Laxman; ZHOU Ning; PU Jun

    2006-01-01

    To observe the effects of simvastatin on nuclear factor kappaB (NF-κB)-DNA binding activity and on the expression of monocyte chemoattractant protein-1 (MCP-1) in atherosclerotic plaque in rabbits and to explore the anti-atherosclerotic properties beyond its lipid-lowering effects.Thirty-six New Zealand male rabbits were randomly divided into low-cholesterol group (LC), highcholesterol group (HC), high-cholesterol+ simvastatin group (HC+S) and then were fed for 12weeks. At the end of theexperiment, standard enzymatic assays, electrophoretic mobility shift assay (EMSA), immunohistochemical staining, and morphometry were performed to observe serum lipids, NF-κB-DNA binding activity, MCP-1 protein expression, intima thickness and plaque area of aorta respectively in all three groups. Our results showed that the serum lipids, NF-κB-DNA binding activity, expression of MCP-1 protein, intima thickness, and plaque area of aorta in the LC and HC+S groups were significantly lower than those in the HC group (P<0.05). There was no significant difference in the serum lipids between the LC and HC+S groups (P>0.05), but the NF-κB-DNA binding activity, the expression of MCP-1 protein and the intima thickness and plaque area of aorta in the HC+S group were significantly decreased as compared to the LC group (P<0.05). This study demonstrated that simvastatin could decrease atherosclerosis by inhibiting the NFκB-DNA binding activity and by reducing the expression of MCP-1 protein.

  3. Study on the changes and clinical significance of serum MMP-9,MCP-1 level in elderly patients with hypertension and obesity%老年高血压伴肥胖患者血清MMP-9、MCP-1水平的变化及其临床意义的研究

    Institute of Scientific and Technical Information of China (English)

    杜健; 冷吉燕; 李修英; 黄慧琳; 邵明柏

    2011-01-01

    Objective To investigate the changes and clinical significance of serum MMP-9,MCP-1 in elderly patients with hypertension and obesity,Methods According to bringing and removing standard option,subjects were classified as control group、simple obesity group、simple hypertension group and obesity-associated hypertension group.Diagnosis of hypertension under the guidance of China hypertension diagnostic criteria in 2005,diagnosis of obesity by body mass index according to BMI≥25kg/m2(Asia-Pacific standards).A general examination and conventional blood glucose.blood lipids and other biochem ical tests were detected in all subjects,serum concentrations of MMP-9 and MCP-1 levels was measured by the Elisa method.Results(1)BMI,IG,LDL-C in control group ,simple obesity group,simple hypertension group and obesity-associated hypertension group,were increased gradually,and compare each of them there is a statistical significance( P < 0.05 ) ;H D L-C in control group,simple obesity group ,simple hypertension group and obesity-associated hypertension group,were decreased gradually,and compare each of them there is a statistical significance ( P<0.05 ) ;FPG ,SBP ,DBP in simple hypertension group and obesity-associated hypertension group higher than control group ,and compare each of them there is a statistical significance (P<0.05);BMI,SBP ,DBP in simple hypertension group and obesity-associated hypertension group higher than siple obesity group ,and compare each of them there is a statistical significance ( P<0.05 );BMI,FPG ,TG ,TC in obesity-associated hypertension group higher than simple hypertension group ,and compare them there is a statistical significance ( P<0.05 ); (2) serum MMP-9 and MCP-1 concentrations in control group ,simple obesity group ,simple hypertension group and obesity-associated hypertnsion group ,were increased gradually ,and compare each of them there is a statistical significance ( P<0.05 ) .Conclusion M M P-9 and M CP-1 play very

  4. Effects of TNF-α on the expression of monocyte chemoattractant protein-1 and the corresponding signal transduction pathway in dental follicle cells

    Directory of Open Access Journals (Sweden)

    Ying-chun BI

    2011-02-01

    Full Text Available Objective To study the effect of different concentration of tumor necrosis factor-α(TNF-α on the expression of monocyte chemoattractant protein-1(MCP-1 and the corresponding signal transduction pathway in human dental follicle cells.Methods The 5th passage of human dental follicle cells were co-incubated with 0(control group,5,10,25,50 and 100 ng/ml TNF-α,respectively,for 6 hours.The contents of MCP-1 in the supernatant were measured by using sandwich ELISA,and the expression of MCP-1 mRNA was determined by reverses transcription polymerase chain reaction(RT-PCR.Furthermore,to determine the corresponding signal transduction pathway,the 5th passage of human dental follicle cells were incubated with 25 μmol/L SB203580 to inhibit p38 mitogen-activated protein kinase(p38MARK,with 50 μmol/L PD98059 to inhibit extracellular signal-regulated kinases(ERK,and with 15 μmol/L SP600125 to inhibit c-Jun N-terminal kinases(JNK for 30min,then incubated with TNF-α(10ng/ml for 6h.MCP-1 mRNA was detected by RT-PCR.Results The results of ELISA revealed that 10-100 ng/ml of TNF-α enhanced MCP-1 secretion(P < 0.05 compared to that in human dental follicle cells without TNF-α treatment.Cells treated with 10-50 ng/ml of TNF-α showed a significant increase of MCP-1 mRNA expression(P < 0.05,and the action was inhibited by SP600125,which was the special inhibitor of c-Jun N-terminal kinase(JNK.Conclusion TNF-α may enhance MCP-1 gene expression and secretion in human dental follicle cells,and the activation of JNK signal transduction pathway is required in this process.

  5. The enhancement of astrocytic-derived monocyte chemoattractant protein-1 induced by the interaction of opiate and HIV tat in HIV-associated dementia

    Institute of Scientific and Technical Information of China (English)

    Xiao Han

    2009-01-01

    HIV-assodated dementia (HAD) is a public health problem and is particularly prevalent in drug abusers. The neuropathogenesis of human immunodeficiency virus (HIV) infection involves a complex cascade of inflammatory events, including monocyte/macrophage infiltration in the brain, glial immune activation and release of neurotoxic substances. In these events, astrocytic-derived monocyte chemoattractant protein-1 (MCP-1) plays an important role, whose release is elevated by HIV transactivator of transcription (HIV tat) and could be further elevated by opiates. This review will also consider some critical factors and events in MCP-1 enhancement induced by the interactions of opiate and HIV tat, including the mediating role of mu opioid receptor (MOR) and CCR2 as well as the possible signal transduction pathways within the cells. Finally, it will make some future perspectives on the exact pathways, new receptors and target cells, and the vulnerability to neurodegeneration with HIV and opiates.

  6. 超声造影联合血清单核细胞趋化蛋白1和细胞黏附分子1检测确定胃癌术前分期%Contrast enhanced ultrasonography with monocyte chemoattractant protein-1 and cellular adhesion molecule-1 detection in preoperative staging of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    张超贤; 秦咏梅; 李光艳

    2016-01-01

    Objective To explore the clinical value of oral ultrasonic contrast agent ultrasonography (OUCAUS) combined with serum monocyte chemoattractant protein-1 (MCP-1) and cell adhesion molecule-1 (CAM-1) measurement in preoperative staging of stomach carcinoma.Methods 800 gastric cancer patients were diagnosed by electric gastroscopy and OUCAUS.The preoperative staging was measured by OUCAUS and compared with pathologic staging,and serum levels of MCP-1 and CAM-1 were measured with ELISA.Results The total accuracy rate of OUCAUS was 79.9% in estimating invasive depth of stomach neoplasm,82.9% in estimating lymphatic metastasis and 88.6% in estimating distant metastasis respectively.The expression levels of MCP-1 and CAM-1 in serum were closely correlated with invasive degree,lymphatic metastasis,distant metastasis and pathologic staging (all P < 0.05).The total accuracy rate of combining OUCAUS and MCP-1,CAM-1 was 93.0 % in estimating invasive depth,93.9% in estimating lymphatic metastasis and 98.6% in estimating distant metastasis respectively.The total accuracy rate of combining OUCAUS and MCP-1,CAM-1 in estimating invasive depth,lymphatic metastasis and distant metastasis was significantly higher than that of by OUCAUS alone.Conclusions MCP-1 and CAM-1 serum levels are closely correlated to pathologic staging of gastric cancer.Combining OUCAUS and MCP-1,CAM-1 can increase the accuracy rate determining invasion and metastasis in gastric cancer.%目的 探讨口服超声助显剂超声检查(oral ultrasonic contrast agent ultrasonography,OUCAUS)联合血清单核细胞趋化蛋白1(monocyte chemoattractant protein-1,MCP-1)和细胞黏附分子1(cell adhesion molecule-1,CAM-1)检测对胃癌术前分期的临床价值.方法 对新乡医学院第一附属医院800例胃癌患者术前行胃镜和OUCAUS检查并进行术前分期,同时用ELISA法检测其术前血清MCP-1和CAM-1水平,并与术后病理分期比较.结果 OUCAUS对胃癌侵犯深度、

  7. Reduction of Monocyte Chemoattractant Protein-1 and Interleukin-8 Levels by Ticlopidine in TNF-α Stimulated Human Umbilical Vein Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Chaur-Jong Hu

    2009-01-01

    Full Text Available Atherosclerosis and its associated complications represent major causes of morbidity and mortality in the industrialized or Western countries. Monocyte chemoattractant protein-1 (MCP-1 is critical for the initiating and developing of atherosclerotic lesions. Interleukin-8 (IL-8, a CXC chemokine, stimulates neutrophil chemotaxis. Ticlopidine is one of the antiplatelet drugs used to prevent thrombus formation relevant to the pathophysiology of atherothrombosis. In this study, we found that ticlopidine dose-dependently decreased the mRNA and protein levels of TNF-α-stimulated MCP-1, IL-8, and vascular cell adhesion molecule-1 (VCAM-1 in human umbilical vein endothelial cells (HUVECs. Ticlopidine declined U937 cells adhesion and chemotaxis as compared to TNF-α stimulated alone. Furthermore, the inhibitory effects were neither due to decreased HUVEC viability, nor through NF-kB inhibition. These results suggest that ticlopidine decreased TNF-α induced MCP-1, IL-8, and VCAM-1 levels in HUVECs, and monocyte adhesion. Therefore, the data provide additional therapeutic machinery of ticlopidine in treatment and prevention of atherosclerosis.

  8. Arctigenin suppresses transforming growth factor-β1-induced expression of monocyte chemoattractant protein-1 and the subsequent epithelial-mesenchymal transition through reactive oxygen species-dependent ERK/NF-κB signaling pathway in renal tubular epithelial cells.

    Science.gov (United States)

    Li, A; Wang, J; Zhu, D; Zhang, X; Pan, R; Wang, R

    2015-01-01

    Transforming growth factor-β1 (TGF-β1) induces expression of the proinflammatory and profibrotic cytokine monocyte chemoattractant protein-1 (MCP-1) in tubular epithelial cells (TECs) and thereby contributes to the tubular epithelial-mesenchymal transition (EMT), which in turn leads to the progression of tubulointerstitial inflammation into tubulointerstitial fibrosis. Exactly how TGF-β1 causes MCP-1 overexpression and subsequent EMT is not well understood. Using human tubular epithelial cultures, we found that TGF-β1 upregulated the expression of reduced nicotinamide adenine dinucleotide phosphate oxidases 2 and 4 and their regulatory subunits, inducing the production of reactive oxygen species. These reactive species activated a signaling pathway mediated by extracellular signal-regulated kinase (ERK1/2) and nuclear factor-κB (NF-κB), which upregulated expression of MCP-1. Incubating cultures with TGF-β1 was sufficient to induce hallmarks of EMT, such as downregulation of epithelial marker proteins (E-cadherin and zonula occludens-1), induction of mesenchymal marker proteins (α-smooth muscle actin, fibronectin, and vimentin), and elevated cell migration and invasion in an EMT-like manner. Overexpressing MCP-1 in cells exposed to TGF-β1 exacerbated these EMT-like changes. Pretreating cells with the antioxidant and anti-inflammatory compound arctigenin (ATG) protected them against these TGF-β1-induced EMT-like changes; the compound worked by inhibiting the ROS/ERK1/2/NF-κB pathway to decrease MCP-1 upregulation. These findings suggest ATG as a new therapeutic candidate to inhibit or even reverse tubular EMT-like changes during progression to tubulointerstitial fibrosis, and they provide the first clues to how ATG may work. PMID:25968940

  9. Arctigenin suppresses transforming growth factor-β1-induced expression of monocyte chemoattractant protein-1 and the subsequent epithelial-mesenchymal transition through reactive oxygen species-dependent ERK/NF-κB signaling pathway in renal tubular epithelial cells.

    Science.gov (United States)

    Li, A; Wang, J; Zhu, D; Zhang, X; Pan, R; Wang, R

    2015-01-01

    Transforming growth factor-β1 (TGF-β1) induces expression of the proinflammatory and profibrotic cytokine monocyte chemoattractant protein-1 (MCP-1) in tubular epithelial cells (TECs) and thereby contributes to the tubular epithelial-mesenchymal transition (EMT), which in turn leads to the progression of tubulointerstitial inflammation into tubulointerstitial fibrosis. Exactly how TGF-β1 causes MCP-1 overexpression and subsequent EMT is not well understood. Using human tubular epithelial cultures, we found that TGF-β1 upregulated the expression of reduced nicotinamide adenine dinucleotide phosphate oxidases 2 and 4 and their regulatory subunits, inducing the production of reactive oxygen species. These reactive species activated a signaling pathway mediated by extracellular signal-regulated kinase (ERK1/2) and nuclear factor-κB (NF-κB), which upregulated expression of MCP-1. Incubating cultures with TGF-β1 was sufficient to induce hallmarks of EMT, such as downregulation of epithelial marker proteins (E-cadherin and zonula occludens-1), induction of mesenchymal marker proteins (α-smooth muscle actin, fibronectin, and vimentin), and elevated cell migration and invasion in an EMT-like manner. Overexpressing MCP-1 in cells exposed to TGF-β1 exacerbated these EMT-like changes. Pretreating cells with the antioxidant and anti-inflammatory compound arctigenin (ATG) protected them against these TGF-β1-induced EMT-like changes; the compound worked by inhibiting the ROS/ERK1/2/NF-κB pathway to decrease MCP-1 upregulation. These findings suggest ATG as a new therapeutic candidate to inhibit or even reverse tubular EMT-like changes during progression to tubulointerstitial fibrosis, and they provide the first clues to how ATG may work.

  10. Effect of folic acid supplementation on levels of circulating Monocyte Chemoattractant Protein-1 and the presence of intravascular ultrasound derived virtual histology thin-cap fibroatheromas in patients with stable angina pectoris.

    Directory of Open Access Journals (Sweden)

    Kjetil H Løland

    Full Text Available BACKGROUND: Virtual Histology Intravascular Ultrasound (VH-IVUS may be used to detect early signs of unstable coronary artery disease. Monocyte Chemoattractant Protein-1 (MCP-1 is linked with coronary atherosclerosis and plaque instability and could potentially be modified by folic acid treatment. METHODS: In a randomized, prospective study, 102 patients with stable angina pectoris (SAP received percutaneous coronary intervention and established medical treatment as well as either homocysteine-lowering folic acid/vitamin B12 (± B6 or placebo (± B6 for 1 year before VH-IVUS was performed. The presence of VH-Thin-Cap Fibroatheroma (VH-TCFA in non-intervened coronary vessels was registered and serum levels of MCP-1 were measured. The patients were subsequently followed for incident myocardial infarction (MI. RESULTS: Patients treated with folic acid/vitamin B12 had a geometric mean (SD MCP-1 level of 79.95 (1.49 versus 86.00 (1.43 pg/mL for patients receiving placebo (p-value 0.34. VH-TCFA lesions were present in 7.8% of patients and did not differ between intervention arms (p-value 0.47. Serum levels of MCP-1 were 1.46 (95% CI 1.12 to 1.92 times higher in patients with VH-TCFA lesions than in those without (p-value 0.005. Afterwards, patients were followed for median 2.1 years and 3.8% experienced a myocardial infarction (MI, which in post-hoc Cox regression analyses was independently predicted by both MCP-1 (P-value 0.006 and VH-TCFA (p-value 0.01. CONCLUSIONS: In patients with SAP receiving established medical treatment, folic acid supplementation is not associated with either presence of VH-TCFA or levels of MCP-1. MCP-1 is however associated with VH-TCFA, a finding corroborated by increased risk for future MI. ClinicalTrials.gov Identifier: NCT00354081.

  11. Effect of a short-term diet and exercise intervention on oxidative stress, inflammation, MMP-9, and monocyte chemotactic activity in men with metabolic syndrome factors.

    Science.gov (United States)

    Roberts, Christian K; Won, Dean; Pruthi, Sandeep; Kurtovic, Silvia; Sindhu, Ram K; Vaziri, Nosratola D; Barnard, R James

    2006-05-01

    The present study was designed to examine the effects of lifestyle modification on key contributing factors to atherogenesis, including oxidative stress, inflammation, chemotaxis, and cell adhesion. Obese men (n = 31), 15 of whom had metabolic syndrome, were placed on a high-fiber, low-fat diet in a 3-wk residential program where food was provided ad libitum and daily aerobic exercise was performed. In each subject, pre- and postintervention fasting blood was drawn for circulating levels of serum lipids, glucose and insulin (for estimation of insulin sensitivity), oxidative stress-generating enzyme myeloperoxidase and marker 8-isoprostaglandin F2alpha, the inflammatory protein C-reactive protein, soluble ICAM-1 as an indicator of endothelial activation, sP-selectin as a marker of platelet activation, the chemokine macrophage inflammatory protein-1alpha, and total matrix metalloproteinase-9. Using subject sera and human aortic endothelial cell culture systems, we measured VCAM-1 cell surface abundance and monocyte chemotactic protein-1, nitric oxide, superoxide, and hydrogen peroxide production in vitro by fluorometric detection. Also determined in vitro was serum-induced, monocyte adhesion and monocyte chemotactic activity. After 3 wk, significant reductions (P fasting glucose, insulin, homeostasis model assessment for insulin resistance, myeloperoxidase, 8-isoprostaglandin F2alpha, C-reactive protein, soluble ICAM-1, soluble P-selectin, macrophage inflammatory protein-1alpha, and matrix metalloproteinase-9 were noted. In vitro, serum-stimulated cellular VCAM-1 expression, monocyte chemotactic protein-1 production, and fluorometric detection of superoxide and hydrogen peroxide production decreased, whereas a concomitant increase in NO production was noted (all P < 0.01). Additionally, both monocyte adhesion (P < 0.05) and MCA (P < 0.01) decreased. Nine of 15 were no longer positive for metabolic syndrome postintervention. Intensive lifestyle modification may

  12. Stability and dynamics of anisotropically-tumbling chemotactic swimmers

    CERN Document Server

    Lushi, Enkeleida

    2016-01-01

    Micro-swimmers such as bacteria E. coli are known to perform random walks known as run-and-tumbles to move up chemo-attractant gradients and as a result aggregate. It is also known that such micro-swimmers can self-organize into macroscopic patterns due to interactions with neighboring cells through the fluidic environment they live in. While the pattern formation resulting from chemotactic and hydrodynamic interactions separately and together have been previously investigated, the effect of the tumbling anisotropy in micro-swimmers has been unexplored. Here we show through linear analysis and full nonlinear simulations that the slight anisotropy in the individual swimmer tumbles can alter the collective pattern formation in non-trivial ways. We show that the tumbling anisotropy diminishes the magnitude of the chemotactic aggregates but may result in more such aggregation peaks.

  13. The enhancement of astrocytic-derived monocyte chemoattractant protein-1 induced by the interaction of opiate and HIV tat in HIV-associated dementia

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    HIV-associated dementia(HAD)is a public health problem and is particularly prevalent in drug abusers.The neuropathogenesis of human immunodeficiency virus(HIV)infection involves a complex cascade of inflammatory events,including monocyte/macrophage infiltration in the brain,glial immune activation and release of neurotoxic substances.In these events,astrocytic-derived monocyte chemoattractant protein-1(MCP-1)plays an important role,whose release is elevated by HIV transactivator of transcription(HIV tat)and...

  14. Pneumocystis carinii major surface glycoprotein induces interleukin-8 and monocyte chemoattractant protein-1 release from a human alveolar epithelial cell line

    DEFF Research Database (Denmark)

    Benfield, T L; Lundgren, Bettina; Shelhamer, J H;

    1999-01-01

    (IL-8) and monocyte chemoattractant protein-1 (MCP-1) from an alveolar epithelial cell line (A549). RESULTS: Incubation of A549 cells with MSG in concentrations from 0.4 to 10 microg mL-1 for 24 h caused dose-dependent increases in IL-8 release (3.4-fold above control, P ..., suggesting that MSG stimulates A549 cells in part through carbohydrate moieties. Dexamethasone significantly inhibited MSG-induced IL-8 release in concentrations of 10-6-10-8 mol L-1 compared with control experiments (P

  15. Maternal circulating leukocytes display early chemotactic responsiveness during late gestation

    Directory of Open Access Journals (Sweden)

    Gomez-Lopez Nardhy

    2013-01-01

    Full Text Available Abstract Background Parturition has been widely described as an immunological response; however, it is unknown how this is triggered. We hypothesized that an early event in parturition is an increased responsiveness of peripheral leukocytes to chemotactic stimuli expressed by reproductive tissues, and this precedes expression of tissue chemotactic activity, uterine activation and the systemic progesterone/estradiol shift. Methods Tissues and blood were collected from pregnant Long-Evans rats on gestational days (GD 17, 20 and 22 (term gestation. We employed a validated Boyden chamber assay, flow cytometry, quantitative real time-polymerase chain reaction, and enzyme-linked immunosorbent assays. Results We found that GD20 maternal peripheral leukocytes migrated more than those from GD17 when these were tested with GD22 uterus and cervix extracts. Leukocytes on GD20 also displayed a significant increase in chemokine (C-C motif ligand 2 (Ccl2 gene expression and this correlated with an increase in peripheral granulocyte proportions and a decrease in B cell and monocyte proportions. Tissue chemotactic activity and specific chemokines (CCL2, chemokine (C-X-C motif ligand 1/CXCL1, and CXCL10 were mostly unchanged from GD17 to GD20 and increased only on GD22. CXCL10 peaked on GD20 in cervical tissues. As expected, prostaglandin F2α receptor and oxytocin receptor gene expression increased dramatically between GD20 and 22. Progesterone concentrations fell and estradiol-17β concentrations increased in peripheral serum, cervical and uterine tissue extracts between GD20 and 22. Conclusion Maternal circulating leukocytes display early chemotactic responsiveness, which leads to their infiltration into the uterus where they may participate in the process of parturition.

  16. Effects of bezafibrate on MCP-1 level in rabbits with atherosclerosis%苯扎贝特对兔动脉粥样硬化单核细胞趋化因子的影响

    Institute of Scientific and Technical Information of China (English)

    李彦琦; 董秋立; 刘海涛; 何敬堂; 郭水英

    2011-01-01

    目的 探讨苯扎贝特对兔动脉粥样硬化(AS)时单核细胞趋化因子( MCP-1)的影响.方法24只新西兰大白兔随机分为高脂组、苯扎贝特组和正常对照组,每组8只.对照组饲以常规颗粒饲料,高脂组饲以高胆固醇饲料(1%胆同醇+5%猪油的颗粒饲料),苯扎贝特组饲以高胆固醇饲料加苯扎贝特[5 mg/( kg·d)],共饲养4个月.HE染色检测兔胸主动脉AS程度,并用免疫组化检测AS斑块的MCP-1蛋白及RT-PCR检测MCP-1 mRNA的转录水平,同时检测血胆固醇和甘油三酯的浓度.结果与高脂组比较,苯扎贝特显著降低了甘油三酯的浓度[(0.7l±0.11) vs (1.72±0.96 )mmol/L,P< 0.05].在苯扎贝特组动脉粥样硬化的程度明显减轻,动脉内膜面积减少[(2.92±0.54) vs (4.16±0.98) mm2,P< 0.051.苯扎贝特治疗组斑块内的MCP-l蛋白表达减少[(19.8±2.2)%vs( 26.2±3.1)%,P<0.01],RT-PCR结果显示,苯扎贝特组MCP-1 mRNA的水平亦明显减少[(0.61±0.06)vs(1.06±0.06),P<0.05].结论使用苯扎贝特明显减轻了动脉粥样硬化程度,其中MCP-1基因及蛋白表达的下降具有重要的作用.%Objective To observe the influence of bezafibrate on monocyte chemoattractant protein-l(MCP-l) level in rabbits with atherosclerosis(AS). Methods Twenty-four New Zealand white rabbits were randomly assigned into 3 groups: high-lipid group, bezafibrate group, and control group, with 8 in each group. The rats in high-lipid group were given high-lipid diet, in bezafibrate group were given high-lipid diet plus bezafibrate [5 mg/(kg ? D)], and in control group were given routine diet. The animals were fed for 4 months. The ascending aorta were harvested, and the morphology was observed using HE staining. The MCP-1 protein and mRNA expression was analyzed by immunohistochemical staining and RT-PCR respectively. The concentrations of serum total cholesterol and triglyceride were also measured. Results The concentration of serum triglyceride was

  17. Effect and its mechanism of rosiglitazone on MCP-1 secretion of rat thoracic aorta smooth muscle cells induced by high-glucose%罗格列酮对高糖诱导大鼠胸主动脉血管平滑肌细胞分泌单核细胞趋化蛋白1的影响及其机制

    Institute of Scientific and Technical Information of China (English)

    谢赟; 王绵; 赵占胜; 梁江燕; 邓永贵; 张力辉; 姚玉霞; 丛斌; 苏胜偶

    2011-01-01

    观察不同葡萄糖浓度培养的大鼠胸主动脉平滑肌细胞分泌单核细胞趋化蛋白1(MCP-1)的变化,以及罗格列酮(RGZ)对其分泌的影响.用不同浓度的葡萄糖和RGZ单独或联合孵育大鼠胸主动脉平滑肌细胞,用ELISA方法 检测培养基中MCP-1的水平,Western Blot方法 检测各组所收集细胞胞浆中NF-κBp65和IκBα的表达. 结果高葡萄糖浓度培养(11.2,22.4mmol/L)的大鼠胸主动脉平滑肌细胞分泌的MCP-1[分别为(340.87±43.92)pg/ml和(664.87±23.07) pg/ml]明显高于对照组[(132.20±5.81)pg/ml],RGZ抑制了高葡萄糖孵育下大鼠胸主动脉平滑肌细胞MCP-1蛋白表达水平并呈浓度依赖性,RGZ拮抗剂GW9662(10 μmol/L)预处理可部分拮抗其作用.MCP-1水平的变化与细胞浆NF-κB、IκB的表达变化相伴随. 结论 高糖可以诱导大鼠胸主动脉平滑肌细胞分泌MCP-1,并呈现浓度依赖性;RGZ可抑制高糖诱导的大鼠胸主动脉平滑肌细胞分泌MCP-1水平,上述作用在一定浓度范围内呈现剂量依赖性.高糖诱导平滑肌细胞分泌MCP-1很可能是通过NF-κB通路来调控的.%Objective To observe the MCP-1 secretion of rat thoracic aorta VSMCs incubated with different concentration of glucose and effects of rosiglitazone (RGZ). Methods The rat thoracic aorta VSMCs were incubated with different concentration of glucose alone or with different concentration of glucose and rosiglitazone, the concentration of MCP-1 in the supernatant was measured with the method of enzyme linked immunoabsorbent assay(ELISA). The levels of NF-kB and IkB protein in the aliquots of the cell extract were examined by Western blot. Results The supernatant concentration of MCP-1 in high glucose groupdl. 2, 22. 4mmol/L)was significantly higher than in control group (P<0. 01). They were (340. 87±43. 92)pg/ml and (664. 87±23. 07)pg/ml respectively, and the level of control group was only (132. 20±5. 81)pg/ml. Rosiglitazone significantly inhibited

  18. Gut Microbiota in Type 2 Diabetes Individuals and Correlation with Monocyte Chemoattractant Protein1 and Interferon Gamma from Patients Attending a Tertiary Care Centre in Chennai, India

    Directory of Open Access Journals (Sweden)

    Premalatha Pushpanathan

    2016-01-01

    Full Text Available Background: Type 2 diabetes mellitus (T2DM and obesity are associated with changes in gut microbiota and characterized by chronic low-grade inflammation. Monocyte chemoattractant protein-1 (MCP-1 and interferon gamma (IFNγ are proinflammatory cytokines which play an important role in the development of T2DM. We undertook this study to analyze the gut microbiota of T2DM and nondiabetic subjects and to determine the profile of MCP 1 and IFNγ in the same subjects attending a tertiary care center in Chennai, Tamil Nadu, India. Methods: The study included 30 subjects with clinical details. Stool and blood samples were collected from all the subjects. DNA was extracted from fecal samples and polymerase chain reaction was done using fusion primers. Metagenomic analysis was performed using ion torrent sequencing. The reads obtained were in FASTA format and reported as operational taxonomic units. Human MCP 1 and IFNγ enzyme linked immunosorbent assay (ELISA were performed for 23 serum samples. Results: The study consisted of 30 subjects; 17 were T2DM and 13 were nondiabetics. The gut microbiota among T2DM consisted predominantly of Gram negative bacteria; Escherichia and Prevotella, when compared with the nondiabetic group with predominantly Gram positive organisms suchas Faecalibacterium, Eubacterium, and Bifidobacterium. The mean MCP-1 values in the diabetic group were 232.8 pg/ml and in the nondiabetic group 170.84 pg/ml. IFNγ (mean 385.5 pg/ml was raised in glycated hemoglobin (HbA1c group of 6.5–7.5% which was statistically significant. Association of Escherichia with T2DM and association of Bifidobacteria in the nondiabetics were also statistically significant. Conclusion: Escherichia counts were elevated in T2DM with HbA1c of 6.5–8.5% which was statistically significant suggesting that lipopolysaccharides present in the cell wall of Gram-negative bacteria may be responsible for low-grade inflammation as evidenced by elevated MCP-1 and

  19. 糖基化终产物通过其受体诱导小鼠足细胞表达单核细胞趋化因子1%Advanced glycation end products-induced MCP-1 expression via its receptor RAGE in mouse podocytes

    Institute of Scientific and Technical Information of China (English)

    顾乐怡; 倪兆慧; 钱家麒; Yasuhiko Tomino

    2006-01-01

    目的了解糖基化终产物(AGE)能否在体外诱导小鼠足细胞表达单核细胞趋化蛋白1(MCP-1)以及其受体RAGE在其中的作用.方法以RT-PCR和ELISA的方法检测AGE、羰甲基化白蛋白(CML)、S100蛋白和RAGE中和抗体对小鼠足细胞的MCP-1的基因和蛋白质表达的影响.结果 (1)未分化和已分化的足细胞都能表达RAGE.(2)AGE和CML以剂量依赖的方式诱导足细胞表达MCP-1mRNA.AGE和CML孵育8 h诱导足细胞产生MCP-1蛋白[分别为(7.44±1.01,8.06±0.96)ng/L],明显高于牛血清白蛋白(BSA)孵育的足细胞[(3.77±0.39)ng/L,均P<0.05],而孵育24 h MCP-1的浓度分别为(87.78±9.32,85.35±9.83和17.95±0.76)ng/L(均P<0.01).(3)RAGE的另外一个配体,S100蛋白,也能以剂量依赖的方式诱导足细胞表达MCP-1 mRNA.RAGE中和抗体完全阻断了AGE、CML和S100的作用.结论 AGE和CML通过RAGE使诱导分化的足细胞表达MCP-1.

  20. Jeans type instability for a chemotactic model of cellular aggregation

    CERN Document Server

    Chavanis, Pierre-Henri

    2008-01-01

    We consider an inertial model of chemotactic aggregation generalizing the Keller-Segel model and we study the linear dynamical stability of an infinite and homogeneous distribution of cells (bacteria, amoebae, endothelial cells,...) when inertial effects are accounted for. These inertial terms model cells directional persistance. We determine the condition of instability and the growth rate of the perturbation as a function of the cell density and the wavelength of the perturbation. We discuss the differences between overdamped (Keller-Segel) and inertial models. Finally, we show the analogy between the instability criterion for biological populations and the Jeans instability criterion in astrophysics.

  1. Expression of monocyte chemoattractant protein and MCP-1 gene in urothelial carcinoma of renal pelvis and its clinical significance%单核细胞趋化蛋白在肾盂尿路上皮癌中的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    白鑫; 高健刚; 侯四川; 孙小庆; 朱磊一

    2011-01-01

    Objective To investigate the monocyte chemoattractant protein (MCP-1) gene expression of urothelial carcinoma of renal pelvis and adjacent normal tissues and the correlation of the incidence and pathological grading of urothelial carcinoma of renal pelvis.Methods Twenty cases of patients with urothelial carcinoma of renal pelvis( 12 cases of male, 8 cases of female) were taken the blood, carcinoma tissues and adjacent normal tissues.Thirty cases of non-cancer patients( 18 cases of male, 12 cases of female) as control group were taken blood samples.Expression of MCP-1 in plasma were detected by ELISA method quantitative determination,and the expression of MCP-1 in urothelial carcinoma of renal pelvis and adjacent normal tissues were investigated by immunohistochemical method.Real-time quantitative PCR was used to detect the expression of MCP-1 RNA.Results MCP-1 in plasma of urothelial carcinoma patients of renal pelvis was(173.4 ±82.1)pg/ml, higher than that of non-tumor group (91.8 ±34.6) pg/ml (P <0.05).Expression of MCP-1 in high-grade urothelial carcinoma of renal pelvis was(254.1 ± 125.8)pg/ml,while in low-grade urothelial carcinoma of renal pelvis was( 151.3 ± 79.5 ) pg/ml.Immunohistochemistry showed that MCP-1 positive rate in urothelial carcinoma of renal pelvis was 90.0% ( 18/20), and in adjacent normal tissues was 65.0% ( 13/20), with significant differences ( P < 0.01 ).Positive expression rate of MCP-1 in high-grade urothelial carcinoma of renal pelvis was 100.0% (4/4) , while in low-grade urothelial carcinoma of renal pelvis was 87.5% ( 14/16 ).Total RNA and mRNA levels of MCP-1 in the urothelial carcinoma of renal pelvis were statistically significant different compared with adjacent normal tissues group (P < 0.05).Conclusion The upregulation of MCP-1 gene expression is likely to play an important role in the incidence and metastasis of the urothelial carcinoma of renal pelvis.%目的 探讨肾盂尿路上皮癌组织单核细胞趋化蛋白(MCP

  2. Diversity of chemotactic heterotrophic bacteria associated with arctic cyanobacteria.

    Science.gov (United States)

    Prasad, Sathish; Pratibha, Mambatta Shankaranarayanan; Manasa, Poorna; Buddhi, Sailaja; Begum, Zareena; Shivaji, Sisinthy

    2013-01-01

    The abundance and diversity of chemotactic heterotrophic bacteria associated with Arctic cyanobacteria was determined. The viable numbers ranged between 10(4) and 10(6) cell g(-1) cyanobacterial biomass. A total of 112 morphotypes, representing 22 phylotypes based on their 16S rRNA sequence similarity were isolated from the samples. All the phylotypes were Gram-negative with affiliation to the proteobacterial and bacteroidetes divisions. Among the 22 phylotypes, 14 were chemotactic to glucose. Majority of the phylotypes were psychrotolerant showing growth up to 30 °C. Representatives of Alphaproteobacteria, the genus Flavobacterium and the gammaproteobacterial Alcanivorax sp, were psychrophilic with growth at or below 18 °C. A significant percentage of phylotypes were pigmented (~68 %), rich in unsaturated membrane fatty acids and tolerated pH values and NaCl concentrations between 5.0-8.0 and 0.15-1.0 M, respectively. The percentages of phylotypes producing extracellular cold-active enzymes at 4 °C were amylase (18.18 %), lipase and urease (45.45 %), caseinase (59.09 %) and gelatinase (31.8 %). PMID:23053490

  3. Corneal organ cultures in tyrosinemia release chemotactic factors.

    Science.gov (United States)

    Lohr, K M; Hyndiuk, R A; Hatchell, D L; Kurth, C E

    1985-05-01

    Corneal inflammation with subsequent scarring and blindness occurs in the inherited human metabolic disease tyrosinemia type II, yet putative inflammatory mediators in this disorder and in the avascular cornea in general are poorly defined. In a Tyr-fed rat model of tyrosinemia type II, intracellular crystals, presumably Tyr, are hypothesized to be responsible for the increased lysosomal activity observed in corneal epithelial lesions. Because polymorphonuclear leukocytes (PMNs) are seen only at the site of these lesions, we used this model to study humoral mediators released from Tyr-fed rat corneal organ cultures. Only Tyr-fed rats developed stromal edema and linear granular opacities in gray edematous corneal epithelium, compatible with a noninfectious keratitis. Electron micrographs confirmed epithelial edema and showed focal epithelial necrosis with PMN invasion of the stroma. Only Tyr-fed rat corneal culture supernatants contained chemotactic activity that was heat labile and moderately trypsin sensitive. Four peaks with varying amounts of chemotactic activity were found on Sephadex G-75 chromatography. Although the identity of these peaks of activity has not yet been established, we suggest that they may be responsible for the PMN infiltration observed in this model of corneal inflammation.

  4. DETECTION OF A NEUTROPHIL CHEMOTACTIC FACTOR IN JAPANESE ENCEPHALITIS PATIENTS

    Directory of Open Access Journals (Sweden)

    Aditi Singh

    2012-12-01

    Full Text Available Japanese encephalitis (JE one of the most common cause of acute encephalitis in tropical regions, has generated much public anxiety in India. An early influx of macrophages followed by neutrophils at the site of injury in different organs in humans and mice has previously been reported. It correlated with production of a neutrophil chemotactic protein derived from macrophages. In the present study out of a total of 324 acute encephalitic patients, admitted in Gandhi memorial and associated hospitals, Lucknow, 121 patients with one or more indicators of JE virus infection were included. Significant pleocytosis (mean TLC value of 126+52 cells / mm3 in CSF and leucocytosis (>11,000 cells/mm3 in peripheral blood was observed at the time of admission. The leucocytosis increased significantly during second week in 67% of patients. The peripheral blood mononuclear cells culture done on alternate days was tested for chemotactic activity (hMDF, which was observed to be highest in second week of illness. The direct detection of hMDF in circulation by dot blot was positive in 92% of acute serum samples, with negligible (12.5% reactivity for convalescent sera. A correlation between the hMDF levels and severity of illness has also been observed.

  5. Excessive Pro-Inflammatory Serum Cytokine Concentrations in Virulent Canine Babesiosis

    DEFF Research Database (Denmark)

    Goddard, Amelia; Leisewitz, Andrew L; Kjelgaard-Hansen, Mads;

    2016-01-01

    admission, prior to any treatment. Cytokine concentrations were assessed using a canine-specific multiplex assay on an automated analyser. Serum concentrations of interleukin (IL)-2, IL-6, IL-8, IL-10, IL-18, granulocyte-macrophage colony stimulating factor (GM-CSF) and monocyte chemotactic protein-1 (MCP-1...

  6. Radioassay of granulocyte chemotaxis. Studies of human granulocytes and chemotactic factors. [/sup 51/Cr tracer technique

    Energy Technology Data Exchange (ETDEWEB)

    Gallin, J.I.

    1974-01-01

    The above studies demonstrate that the /sup 51/Cr radiolabel chemotactic assay is a relatively simple and objective means for studying leukocyte chemotaxis in both normal and pathological conditions. Application of this method to studies of normal human chemotaxis revealed a relatively narrow range of normal and little day-to-day variability. Analysis of this variability revealed that there is more variability among the response of different granulocytes to a constant chemotactic stimulus than among the chemotactic activity of different sera to a single cell source. Utilizing the /sup 51/Cr radioassay, the abnormal granulocyte chemotactic behavior reported in Chediak-Higashi syndrome and a patient with recurrent pyogenic infections and mucocutaneous candidiasis has been confirmed. The /sup 51/Cr chemotactic assay has also been used to assess the generation of chemotactic activity from human serum and plasma. The in vitro generation of two distinct chemotactic factors were examined; the complement product (C5a) and kallikrein, an enzyme of the kinin-generating pathway. Kinetic analysis of complement-related chemotactic factor formation, utilizing immune complexes or endotoxin to activate normal sera in the presence or absence of EGTA as well as kinetic analysis of activation of C2-deficient human serum, provided an easy means of distinguishing the classical (antibody-mediated) complement pathway from the alternate pathway. Such kinetic analysis is necessary to detect clinically important abnormalities since, after 60 min of generation time, normal chemotactic activity may be present despite complete absence or inhibition of one complement pathway. The chemotactic factor generated by either pathway of complement activation appears to be predominately attributable to C5a.

  7. Hydrogen sulfide suppresses oxidized low-density lipoprotein (ox-LDL)-stimulated monocyte chemoattractant protein 1 generation from macrophages via the nuclear factor κB (NF-κB) pathway.

    Science.gov (United States)

    Du, Junbao; Huang, Yaqian; Yan, Hui; Zhang, Qiaoli; Zhao, Manman; Zhu, Mingzhu; Liu, Jia; Chen, Stella X; Bu, Dingfang; Tang, Chaoshu; Jin, Hongfang

    2014-04-01

    This study was designed to examine the role of hydrogen sulfide (H2S) in the generation of oxidized low-density lipoprotein (ox-LDL)-stimulated monocyte chemoattractant protein 1 (MCP-1) from macrophages and possible mechanisms. THP-1 cells and RAW macrophages were pretreated with sodium hydrosulfide (NaHS) and hexyl acrylate and then treated with ox-LDL. The results showed that ox-LDL treatment down-regulated the H2S/cystathionine-β-synthase pathway, with increased MCP-1 protein and mRNA expression in both THP-1 cells and RAW macrophages. Hexyl acrylate promoted ox-LDL-induced inflammation, whereas the H2S donor NaHS inhibited it. NaHS markedly suppressed NF-κB p65 phosphorylation, nuclear translocation, DNA binding activity, and recruitment to the MCP-1 promoter in ox-LDL-treated macrophages. Furthermore, NaHS decreased the ratio of free thiol groups in p65, whereas the thiol reductant DTT reversed the inhibiting effect of H2S on the p65 DNA binding activity. Most importantly, site-specific mutation of cysteine 38 to serine in p65 abolished the effect of H2S on the sulfhydration of NF-κB and ox-LDL-induced NF-κB activation. These results suggested that endogenous H2S inhibited ox-LDL-induced macrophage inflammation by suppressing NF-κB p65 phosphorylation, nuclear translocation, DNA binding activity, and recruitment to the MCP-1 promoter. The sulfhydration of free thiol group on cysteine 38 in p65 served as a molecular mechanism by which H2S inhibited NF-κB pathway activation in ox-LDL-induced macrophage inflammation.

  8. 有氧运动加谷氨酰胺补充对2型糖尿病大鼠骨骼肌炎症因子NF-κB、MPO及MCP-1基因表达的影响%Effect of Aerobic Exercise plus Glutamine Supplement on Expression of Muscle NF-κB,MPO and MCP-1 mRNA of Type 2 Diabetes

    Institute of Scientific and Technical Information of China (English)

    付德荣; 孙小华; 刘承宜; 廖八根; 李鹏博; 田祯祥

    2012-01-01

    目的:观察长期有氧运动联合谷氨酰胺(Gln)补充对2型糖尿病(T2DM)大鼠骨骼肌炎症因子核转录因子-κB(NF-κB)、单核细胞趋化蛋白-1(MCP-1)、髓过氧化物酶(MPO)基因表达及空腹血糖(FBG)、血胰岛素(ISN)及胰高血糖素样肽-1(GLP-1)的影响.方法:将雄性Sprague-Dawley大鼠60只(179.8±19.2 g)随机分为健康对照组(C组,26只)和糖尿病造模组(D组,34只).对照组普通饲料喂养,糖尿病组高脂喂养.4周后糖尿病组大鼠腹腔注射35 mg/kg链脲佐菌素诱导T2DM.成模后两组进一步随机分为:安静组(CQ,DQ)、运动组(CE,DE)、Gln组(CG,DG)、运动加Gln组(CEG,DEG).运动组大鼠进行6周游泳运动.Gln组改用含2%(w/w) L-Gln饲料喂养.腹主动脉取血测FBG、ISN及GLP-1水平,腓肠肌测NF-κB、MPO及MCP-1的mRNA的表达.结果:安静状态下T2DM大鼠(DQ)骨骼肌NF-κB、MCP-1及MPO的mRNA表达量及血FBG值显著高于对照组(CQ),血ISN和GLP-1水平明显低于对照组.6周游泳运动(DE)或Gln补充(DG)可明显降低T2DM大鼠骨骼肌NF-κB、MCP-1及MPO的mRNA表达和血FBG水平,并增加ISN及GLP-1水平.6周游泳运动联合Gln补充(DEG)时,降低T2DM大鼠骨骼肌NF-κB mRNA表达的效应显著高于单纯Gln补充组(DG),但与单纯运动组(DE)相似;对MCP-1 mRNA的抑制与单纯Gln补充组(DG)相似,但明显高于单纯运动组(DE);对MPO mRNA表达的影响与单纯运动组(DE)或单纯Gln补充组(DG)相似;降低FBG水平、增加GLP-1的作用较单纯运动组(DE)或Gln补充组(DG)明显,增加ISN的效应与单纯运动组(DE)或Gln补充组(DG)相似.结论:长期有氧运动或Gln补充明显抑制T2DM大鼠骨骼肌炎症因子NF-κB、MPO及MCP-1的基因表达,增加GLP-1及ISN的分泌量,降低FBG值.当运动联合Gln补充时,降低T2DM骨骼肌炎症因子产生、升高GLP-1及降低FBG的效应较运动或Gln单因素作用时明显,对ISN分泌的影响与单纯运动或Gln补充相似.

  9. Significance of Expression of Monocyte Chemoattractant Protein-1 in Renal Biopsy Tissue from Immunoglobulin A Nephropathy%IgA肾病患者肾组织单核细胞趋化蛋白-1表达的意义

    Institute of Scientific and Technical Information of China (English)

    杨晓庆; 高进

    2011-01-01

    目的 探讨原发性IgA肾病(IgAN)患者肾组织单核细胞趋化蛋白-1(MCP-1)的表达变化.方法 选择经皮肾组织穿刺活检确诊为IgAN的患者40例.根据肾脏病理Lee氏分级(Ⅰ~Ⅴ级)将纳入研究的患者分为2组:A组20例,病理分级为Ⅰ~Ⅲ级;B组20例,病理分级为Ⅳ~Ⅴ级.对照组20例标本选取手术切除的肾肿瘤、肾囊肿患者远离病变组织的正常肾组织.同时将肾组织的肾小管和肾间质按照Katafuchi标准分为无间质病变组21例,轻度间质病变组8例,中度间质病变组19例和重度间质病变组12例.均采用免疫组织化学方法测定其肾组织中MCP-1的表达(以灰度值反映),观察其肾组织切片的染色强度及染色透光度,灰度值大则MCP-1表达少,反之则表达多.结果 根据肾脏病理Lee分级分组,各组灰度值比较:B组灰度值(68.08±2.37)与A组灰度值(74.50±3.27)比较、B组与对照组灰度值(81.98±3.21)比较、A 组与对照组比较,差异均有统计学意义(Pa<0.01);根据Katafuchi标准分组,无间质病变组、轻度间质病变组、中度间质病变组及重度间质病变组灰度值分别为82.03±3.13、76.44±2.01、71.49±1.69、66.54±1.23,各组比较差异均有统计学意义(Pa<0.01).结论 MCP-1可反映原发性IgAN患者肾组织的病理损害程度,且表达水平与肾组织损害程度有关.%objective To explore the expression of monocyte chemoattractant protein - 1( MCP - 1) in renal biopsy tissue from IgA nephropathy (IgAN) patients. Methods Forty patients were diagnosed as IgAN by renal biopsy, and they were divided into 2 groups according to Lee classification ( Ⅰ - Ⅴ grade) :group A included 20 cases( Lee Ⅰ - Ⅲ grade) and group B included the other 20 cases( Lee Ⅳ - Ⅴgrade). The control group included 20 patients diagnosed as having normal kidney tissue by renal biopsy, whose kidney tissue came from patients whose renal tumors and renal cysts were removed. In the

  10. Controlling neural activity in Caenorhabditis elegans to evoke chemotactic behavior

    Science.gov (United States)

    Kocabas, Askin; Shen, Ching-Han; Guo, Zengcai V.; Ramanathan, Sharad

    2013-03-01

    Animals locate and track chemoattractive gradients in the environment to find food. With its simple nervous system, Caenorhabditis elegans is a good model system in which to understand how the dynamics of neural activity control this search behavior. To understand how the activity in its interneurons coordinate different motor programs to lead the animal to food, here we used optogenetics and new optical tools to manipulate neural activity directly in freely moving animals to evoke chemotactic behavior. By deducing the classes of activity patterns triggered during chemotaxis and exciting individual neurons with these patterns, we identified interneurons that control the essential locomotory programs for this behavior. Notably, we discovered that controlling the dynamics of activity in just one interneuron pair was sufficient to force the animal to locate, turn towards and track virtual light gradients.

  11. Phenomenological understanding of aggregation and dispersion of chemotactic cells

    CERN Document Server

    Iwasa, Masatomo

    2011-01-01

    We present a simple model that describes the motion of a single chemotactic cell exposed to a traveling wave of the chemoattractant. The model incorporates two types of responses to stimulation by the chemoattractant, i.e., change in polarity and change in motility of the cell. The periodic change in motility is assumed to be induced by the periodic stimulation by the chemoattractant on the basis of previous observations. Consequently, net migration of the cell occurs in a particular direction with respect to wave propagation, which explains the migration of Dictyostelium cells in aggregation processes. The difference between two time delays from the stimulation to the two responses and the wave frequency determined by the frequency of the secretion of the chemoattractant are important parameters that determine the direction of migration and the effective interaction between cells in a population. This result explains the dispersed state of a population of vegetative cells and cells in preaggregation without ...

  12. Thrombin cleavage of osteopontin disrupts a pro-chemotactic sequence for dendritic cells, which is compensated by the release of its pro-chemotactic C-terminal fragment.

    Science.gov (United States)

    Shao, Zhifei; Morser, John; Leung, Lawrence L K

    2014-09-26

    Thrombin cleavage alters the function of osteopontin (OPN) by exposing an integrin binding site and releasing a chemotactic C-terminal fragment. Here, we examined thrombin cleavage of OPN in the context of dendritic cell (DC) migration to define its functional domains. Full-length OPN (OPN-FL), thrombin-cleaved N-terminal fragment (OPN-R), thrombin- and carboxypeptidase B2-double-cleaved N-terminal fragment (OPN-L), and C-terminal fragment (OPN-CTF) did not have intrinsic chemotactic activity, but all potentiated CCL21-induced DC migration. OPN-FL possessed the highest potency, whereas OPNRAA-FL had substantially less activity, indicating the importance of RGD. We identified a conserved (168)RSKSKKFRR(176) sequence on OPN-FL that spans the thrombin cleavage site, and it demonstrated potent pro-chemotactic effects on CCL21-induced DC migration. OPN-FLR168A had reduced activity, and the double mutant OPNRAA-FLR168A had even lower activity, indicating that these functional domains accounted for most of the pro-chemotactic activity of OPN-FL. OPN-CTF also possessed substantial pro-chemotactic activity, which was fully expressed upon thrombin cleavage and its release from the intact protein, because OPN-CTF was substantially more active than OPNRAA-FLR168A containing the OPN-CTF sequence within the intact protein. OPN-R and OPN-L possessed similar potency, indicating that the newly exposed C-terminal SVVYGLR sequence in OPN-R was not involved in the pro-chemotactic effect. OPN-FL and OPN-CTF did not directly bind to the CD44 standard form or CD44v6. In conclusion, thrombin cleavage of OPN disrupts a pro-chemotactic sequence in intact OPN, and its loss of pro-chemotactic activity is compensated by the release of OPN-CTF, which assumes a new conformation and possesses substantial activity in enhancing chemokine-induced migration of DCs. PMID:25112870

  13. Chemotactic Activity on Human Neutrophils to Streptococcus mutans

    Directory of Open Access Journals (Sweden)

    Tetiana Haniastuti

    2013-07-01

    Full Text Available Objective: The aim of this study was to evaluate chemotactic activity o neutrophil to S. mutans. Chemotaxis assay was performed in blind well chambers. Materials and Methods: Hanks balanced salt solution (HBSS containing 106 S. mutans,  108 S. mutans, 10-8 M fMLP, or HBSS alone were placed in the lower wells of the chamber and covered with polycorbonate membrane filter. Neutrophils suspension (2x105 cells was then placed in the upper compartment. After incubation for 60 mins at 37ºC in a humidified atmosphere with 5% CO2, the filters were removed and stained with Giemsa. Result: ANOVA revealed statistically significant differences among groups (p<0.05, indicating that S. mutans induced neutrophils chemotaxis. The number of neutrophils migration in response to 108 S. mutans and 106 S. mutans were signifiantly greater compared to fMLP (p<0.05. Conclusion: S. mutans may activate human neutrophils, resulting in the chemotaxis of the neutrophils.DOI: 10.14693/jdi.v16i2.99

  14. Human sperm pattern of movement during chemotactic re-orientation towards a progesterone source

    Institute of Scientific and Technical Information of China (English)

    Cecilia Soledad Blengini; Maria Eugenia Teves; Diego Rafael Unates; Hector Alejandro Guidobaldi; Laura Virginia Gatica; Laura Cecilia Giojalas

    2011-01-01

    @@ Human spermatozoa may chemotactically find out the egg by following an increasing gradient of attractant molecules.Although human spermatozoa have been observed to show several of the physiological characteristics of chemotaxis,the chemotactic pattern of movement has not been easy to describe.However,it is apparent that chemotactic cells may be identified while returning to the attractant source.This study characterizes the pattern of movement of human spermatozoa during chemotactic re-orientation towards a progesterone source,which is a physiological attractant candidate.By means of videomicroscopy and image analysis,a chemotactic pattern of movement was identified as the spermatozoon returned towards the source of a chemotactic concentration of progesterone (10 pmol l-1).First,as a continuation of its original path,the spermatozoon swims away from the progesterone source with linear movement and then turns back with a transitional movement that can be characterized by an increased velocity and decreased linearity.This sperm behaviour may help the spermatozoon to re-orient itself towards a progesterone source and may be used to identify the few cells that are undergoing chemotaxis at a given time.

  15. Enhanced Retention of Chemotactic Bacteria in a Pore Network with Residual NAPL Contamination.

    Science.gov (United States)

    Wang, Xiaopu; Lanning, Larry M; Ford, Roseanne M

    2016-01-01

    Nonaqueous-phase liquid (NAPL) contaminants are difficult to eliminate from natural aquifers due, in part, to the heterogeneous structure of the soil. Chemotaxis enhances the mixing of bacteria with contaminant sources in low-permeability regions, which may not be readily accessible by advection and dispersion alone. A microfluidic device was designed to mimic heterogeneous features of a contaminated groundwater aquifer. NAPL droplets (toluene) were trapped within a fine pore network, and bacteria were injected through a highly conductive adjacent macrochannel. Chemotactic bacteria (Pseudomonas putida F1) exhibited greater accumulation near the pore network at 0.5 m/day than both the nonchemotactic control and the chemotactic bacteria at a higher groundwater velocity of 5 m/day. Chemotactic bacteria accumulated in the vicinity of NAPL droplets, and the accumulation was 15% greater than a nonchemotactic mutant. Indirect evidence showed that chemotactic bacteria were retained within the contaminated low-permeability region longer than nonchemotactic bacteria at 0.25 m/day. This retention was diminished at 5 m/day. Numerical solutions of the bacterial-transport equations were consistent with the experimental results. Because toluene is degraded by P. putida F1, the accumulation of chemotactic bacteria around NAPL sources is expected to increase contaminant consumption and improve the efficiency of bioremediation.

  16. Collective Chemotactic Dynamics in the Presence of Self-Generated Fluid Flows

    CERN Document Server

    Lushi, Enkeleida; Shelley, Michael J

    2012-01-01

    In micro-swimmer suspensions locomotion necessarily generates fluid motion, and it is known that such flows can lead to collective behavior from unbiased swimming. We examine the complementary problem of how chemotaxis is affected by self-generated flows. A kinetic theory coupling run-and-tumble chemotaxis to the flows of collective swimming shows separate branches of chemotactic and hydrodynamic instabilities for isotropic suspensions, the first driving aggregation, the second producing increased orientational order in suspensions of "pushers" and maximal disorder in suspensions of "pullers". Nonlinear simulations show that hydrodynamic interactions can limit and modify chemotactically-driven aggregation dynamics. In puller suspensions the dynamics form aggregates that are mutually-repelling due to the non-trivial flows. In pusher suspensions chemotactic aggregation can lead to destabilizing flows that fragment the regions of aggregation.

  17. Plasma Monocyte Chemoattractant Protein-1 Level as a Predictor of the Severity of Community-Acquired Pneumonia.

    Science.gov (United States)

    Yong, Kok-Khun; Chang, Jer-Hwa; Chien, Ming-Hsien; Tsao, Shih-Ming; Yu, Ming-Chih; Bai, Kuan-Jen; Tsao, Thomas Chang-Yao; Yang, Shun-Fa

    2016-01-29

    Monocyte chemoattractant protein (MCP)-1 increases in the serum of immunocompetent patients with community-acquired pneumonia (CAP). However, the correlation between the circulating level of MCP-1 and severity of CAP remains unclear. This study investigated differential changes in the plasma MCP-1 levels of patients with CAP before and after an antibiotic treatment and further analyzes the association between the CAP severity and MCP-1 levels. We measured the plasma MCP-1 levels of 137 patients with CAP and 74 healthy controls by using a commercial enzyme-linked immunosorbent assay. Upon initial hospitalization, Acute Physiology and Chronic Health Evaluation II (APACHE II); confusion, urea level, respiratory rate, blood pressure, and age of >64 years (CURB-65); and pneumonia severity index (PSI) scores were determined for assessing the CAP severity in these patients. The antibiotic treatment reduced the number of white blood cells (WBCs) and neutrophils as well as the level of C-reactive protein (CRP) and MCP-1. The plasma MCP-1 level, but not the CRP level or WBC count, correlated with the CAP severity according to the PSI (r = 0.509, p < 0.001), CURB-65 (r = 0.468, p < 0.001), and APACHE II (r = 0.360, p < 0.001) scores. We concluded that MCP-1 levels act in the development of CAP and are involved in the severity of CAP.

  18. Draft Genome Sequence of Halomonas sp. KHS3, a Polyaromatic Hydrocarbon-Chemotactic Strain

    OpenAIRE

    Gasperotti, Ana Florencia; Studdert, Claudia Alicia; Revale, Santiago; Herrera Seitz, María Karina

    2015-01-01

    The draft genome sequence of Halomonas sp. KHS3, isolated from seawater from Mar del Plata harbor, is reported. This strain is able to grow using aromatic compounds as a carbon source and shows strong chemotactic response toward these substrates. Genes involved in motility, chemotaxis, and degradation of aromatic hydrocarbons were identified.

  19. Enhanced Retention of Chemotactic Bacteria in a Pore Network with Residual NAPL Contamination

    Science.gov (United States)

    Ford, R.; Wang, X.

    2013-12-01

    Nonaqueous phase liquid (NAPL) contaminants are difficult to eliminate from natural aquifers due, in part, to the heterogeneous structure of the soil matrix. Residual NAPL ganglia remain trapped in regions where the hydraulic conductivity is relatively low. Bioremediation processes depend on adequate mixing of microbial populations and the groundwater contaminants that they degrade. The ability of bacteria to sense a chemical gradient and swim preferentially toward locations of higher concentration, known as chemotaxis, can enhance the mixing of bacteria with contaminant sources that may not be readily accessible by advection and dispersion alone. The impact of chemotaxis on bacterial abundance within a low conductivity NAPL-contaminated region of a well-characterized porous matrix was investigated. A microfluidic device was designed to mimic heterogeneous features of a contaminated groundwater system. NAPL ganglia (toluene) were trapped within a fine pore network, and bacteria were injected into the system through a highly conductive adjacent channel. Chemotactic bacteria (P. putida F1) migrated preferentially towards and accumulated in the vicinity of NAPL contaminant sources. The accumulation of chemotactic bacteria was 15% greater in comparison to a nonchemotactic mutant (P. putida F1 CheA). Bacteria in the microfluidic device were subjected to different flow velocities from 0.25 to 5 m/d encompassing the range of typical groundwater flow rates. Chemotactic bacteria exhibited greater accumulation near the intersection between the macrochannel and the porous network at a flow velocity of 0.5 m/d than both the nonchemotactic mutant control and the chemotactic bacteria at a higher flow velocity of 5 m/d. Breakthrough curves observed at the outlet provided indirect evidence that chemotactic bacteria were retained within the contaminated low permeable region for a longer time than the nonchemotactic bacteria at a flow velocity of 0.25 m/d. This retention was

  20. RANTES and chemotactic activity in synovial fluids from patients with rheumatoid arthritis and osteoarthritis.

    Science.gov (United States)

    Stanczyk, Joanna; Kowalski, Marek L; Grzegorczyk, Janina; Szkudlinska, Barbara; Jarzebska, Marzanna; Marciniak, Marek; Synder, Marek

    2005-12-14

    A massive accumulation of inflammatory cells in synovial tissues is a major pathological feature of rheumatoid arthritis (RA). Neutrophiles dominate synovial fluid while rheumatoid synovium is infiltrated with mononuclear cells. Mechanisms regulating influx of particular subpopulations of leukocytes into articular cavity and synovium compartment are not completely defined. An increasing amount of data supports a crucial role of a C-C chemokine RANTES in the RA pathogenesis. Our objective is to evaluate chemotactic activity for neutrophils (NCA), lymphocytes (LCA), and monocytes (MoCA) in SFs obtained from patients with RA and osteoarthritis (OA). We also aimed to characterise the relation between chemotactic activity, RANTES, and percentage distribution of leukocytes in SF. SFs from 11 patients with RA and 6 with OA were included in the study. Modified microchamber Boyden method was employed to assess chemotactic activity. Cytological and biochemical analysis of SF was performed. RANTES was measured with ELISA. Rheumatoid SFs were rich in cells with predominance of neutrophiles while osteoarthritic fluids were lymphocytic. RA SFs were also characterised by increased lactoferrin level. Both NCA and LCA were higher in SF from patients with RA (62 +/- 12 and 24 +/- 6 cells/HPF, resp) as compared to patients with OA (23 +/- 6; P < .05 and 6 +/- 2 cells/HPF; P < 0.05). The chemoattractive effect of RA SF was more pronounced on neutrophiles than on lymphocytes. RA SF expressed high RANTES levels (145+/- 36 pg/mL), while OA SF was characterised by only trace amount of this chemokine (2 +/- 1 pg/mL). We found positive correlation of RANTES with chemotactic activity for mononuclear cells (LCA + MoCA; R = 0.61; P < .05). Surprisingly, RANTES correlated also positively with neutrophiles number (R = 0.77; P < 0.001). Rheumatoid SF possesses strong chemotactic potency for leukocytes. RANTES is overexpressed in RA SF and is a potential mediator influencing intensity and

  1. Chemotactic effect of urokinase-type plasminogen activator on mouse spermatozoa in vitro

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The aim of this study is to investigate the chemotactic effect of urokinase-type plasminogen activator (uPA)on mouse spermatozoa.Capillary assays were applied to study the chemotactic activity of ascending and descending gradients of uPA.Firstly,the chemotactic effect of an ascending gradient of uPA on mouse spermatozoa was observed by counting the number of spermatozoa that migrated into the capillary after incubation with uPA for 5,10,20,and 30 min,respectively,compared with that after incubation with F10.Twenty minutes was a suitable incubation time to obtain a plateau of sperm accumulation.Meanwhile,to confirm the specific effect of uPA on mouse sperm chemotaxis,uPA inhibitor (PAI-1)and anti-uPAR rabbit IgG were added to the test solution containing 20 U/mL uPA,respectively.To exclude the possibility that PAI-1 and anti-uPAR rabbit IgG may affect sperm accumulation nonspecifically,PAIl and anti-uPAR rabbit IgG were added to F10,respectively.It was found that the chemotactic effect of uPA was neutralized completely by PAI-1 and anti-uPAR rabbit IgG.PAI-1 and anti-uPAR rabbit IgG had no neutralizing effect on the sperm chemotactic effect.Lastly,the sperm chemotaxis response to a descending gradient of uPA was also observed.Taken together,the results suggest that uPA can induce sperm chemotaxis in vitro by binding to its receptor on the sperm membrane and may act as a chemoattractant in precontacting sperm-egg communication thereby increasing the chance encounter of spermatozoa and eggs.

  2. Induction of Monocyte Chemoattractant Proteins in Macrophages via the Production of Granulocyte-macrophage Colony Stimulating Factor by Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Teizo eYoshimura

    2016-01-01

    Full Text Available Monocyte chemoattractant protein-1 (MCP-1/CCL2 plays an important role in the initiation and progression of cancer. We previously reported that in 4T1 murine breast cancer, non-tumor stromal cells, including macrophages, were the major source of MCP-1. In the present study, we analyzed the potential mechanisms by which MCP-1 is upregulated in macrophages infiltrating 4T1 tumors. We found that cell-free culture supernatants of 4T1 cells (4T1-sup markedly upregulated MCP-1 production by peritoneal inflammatory macrophages. 4T1-sup also upregulated other MCPs, such as MCP-3/CCL7 and MCP-5/CCL12, but modestly neutrophil chemotactic chemokines, such as KC/CXCL1 or MIP-2/CXCL2. Physicochemical analysis indicated that an approximately 2 to 3 kDa 4T1 cell product was responsible for the capacity of 4T1-sup to upregulate MCP-1 expression by macrophages. A neutralizing antibody against granulocyte-macrophage-colony stimulating factor (GM-CSF, but not macrophage-colony stimulating factor, almost completely abrogated MCP-1-inducing activity of 4T1-sup, and recombinant GM-CSF potently up-regulated MCP-1 production by macrophages. The expression levels of GM-CSF in 4T1 tumors in vivo were higher than other tumors, such as Lewis lung carcinoma. Treatment of mice with anti-GM-CSF antibody significantly reduced the growth of 4T1 tumors at the injection sites but did not reduce MCP-1 production or lung metastasis in tumor-bearing mice. These results indicate that 4T1 cells have the capacity to directly up-regulate MCP-1 production by macrophages by releasing GM-CSF; however, other mechanisms are also involved in increased MCP-1 levels in the 4T1 tumor microenvironment.

  3. The interaction between different types of activated RAW 264.7 cells and macrophage inflammatory protein-1 alpha

    International Nuclear Information System (INIS)

    Two major ways of macrophage (MΦ) activation can occur in radiation-induced pulmonary injury (RPI): classical and alternative MΦ activation, which play important roles in the pathogenesis of RPI. MΦ can produce chemokine MΦ inflammatory protein-1α (MIP-1α), while MIP-1α can recruit MΦ. The difference in the chemotactic ability of MIP-1α toward distinct activated MΦ is unclear. We speculated that there has been important interaction of MIP-1α with different activated MΦ, which might contribute to the pathogenesis of RPI. Classically and alternatively activated MΦ were produced by stimulating murine MΦ cell line RAW 264.7 cells with three different stimuli (LPS, IL-4 and IL-13); Then we used recombinant MIP-1α to attract two types of activated MΦ. In addition, we measured the ability of two types of activated MΦ to produce MIP-1α at the protein or mRNA level. Chemotactic ability of recombinant MIP-1α toward IL-13-treated MΦ was the strongest, was moderate for IL-4-treated MΦ, and was weakest for LPS-stimulated MΦ (p < 0.01). The ability of LPS-stimulated MΦ to secrete MIP-1α was significantly stronger than that of IL-4-treated or IL-13-treated MΦ (p < 0.01). The ability of LPS-stimulated MΦ to express MIP-1α mRNA also was stronger than that of IL-4- or IL-13-stimulated MΦ (p < 0.01). The chemotactic ability of MIP-1α toward alternatively activated MΦ (M2) was significantly greater than that for classically activated MΦ (M1). Meanwhile, both at the mRNA and protein level, the capacity of M1 to produce MIP-1α is better than that of M2. Thus, chemokine MIP-1α may play an important role in modulating the transition from radiation pneumonitis to pulmonary fibrosis in vivo, through the different chemotactic affinity for M1 and M2

  4. Homocysteine induces production of monocyte chemoattractant protein-1 and interleukin-8 in cultured human whole blood

    Institute of Scientific and Technical Information of China (English)

    Xiao-kunZENG; DanielGREMICK; XianWANG

    2004-01-01

    AIM: To investigate whether increased plasma L-homocysteine (Hcy) level could promote monocyte chemoattract antprotein-1 (MCP-1) and interleukin-8 (IL-8) in cultured whole blood. METHODS: Human whole blood or differenttype of peripheral blood cells from health volunteers were incubated with Hcy and/or the inhibitors. MCP-1 and IL-8 level were measured by ELISA assay. RESULTS: Hcy 10-1000 μmol/L induced production of MCP-1and IL-8 in cultured human whole blood (P<0.05). The major cellular source of these chemokines comed from monocytes. Meanwhile,Hcy also promoted the upregulation of MPO level even at the 10 μmol/L in the cultured whole blood.The intracellular ROS, particular the OH radicals, play extremely important role in the Hcy-induced MCP-1 and IL-8 production. CONCLUSION: Increased Hcy level in plasma (hyperhomocysteinemia) induced MCP-1 and IL-8secretion in cultured human whole blood, especially in monocytes via oxidative stress mechanism,

  5. Effect of Hydrogen Sulfide Inhibiting Monocyte Chemoattractant Protein -1 Secretion in Human Macrophages Stimulated by Oxidized Low Density Lipoprotein%硫化氢抑制氧化型低密度脂蛋白诱导的人巨噬细胞单核细胞趋化蛋白-1分泌的作用

    Institute of Scientific and Technical Information of China (English)

    张巧丽; 闫辉; 唐朝枢; 金红芳; 杜军保

    2012-01-01

    目的 研究气体信号分子硫化氢(H2S)对氧化型低密度脂蛋白(ox-LDL)诱导的人单核细胞白血病细胞(THP-1)来源的人巨噬细胞单核细胞趋化蛋白-1(MCP-1)分泌的影响.方法 将THP-1来源的人巨噬细胞分为4组:正常对照组、ox-LDL组、ox-LDL+ H2S 100组及ox-LDL+H2S 500组.正常对照组:细胞于基础培养基中培养48 h;ox-LDL组:在基础培养基中加入50mg ·L-1ox-LDL,培养48 h;ox-LDL+ H2S 100组在基础培养基中先加入100 μmol·L-1 NaHS,孵育30 min后再加入50 mg·L-1 ox-LDL,培养48 h;ox-LDL+H2S 500组在基础培养基中先加入500 μmol·L-1 NaHS,孵育30 min后再加入50 mg·L-1 ox-LDL,培养48h.用ELISA法检测细胞上清液中MCP-1水平.结果 与正常对照组[(34.58±6.77)μmol·L-1]比较,ox-LDL组[(66.27±7.29)μm0l·L-1]、ox-LDL+H2S100组[(49.45±3.08) μmol·L-1]及ox-LDL+H2S 500组[(46.64±5.47) μmol·L-1]细胞上清液中MCP-1水平均明显升高(Pa<0.05);与ox-LDL组比较,ox-LDL+ H2S 100组及ox-LDL+ H2S 500组细胞上清液中MCP-1水平均明显降低(Pa<0.05).ox-LDL+ H2S 100组细胞上清液中MCP-1水平与ox-LDL+ H2S 500组比较差异无统计学意义(P>0.05).结论 ox-LDL可诱导人巨噬细胞MCP-1分泌增加;给予外源性H2S的供体NaHS可明显抑制ox-LDL诱导的MCP-1分泌增加.%Objective To explore the effect of hydrogen sulfide( H2S) on oxidized - low density lipoprotein(ox - LDL) - stimulated monocyte chemoattractant protein - 1 ( MCP - 1) secretion in THP - 1 - derived macrophage. Methods THP - 1 - derived macrophages were divided into 4 groups:normal control group,ox - LDL group,ox - LDL + H2S 100 group and ox - LDL + H2S 500 group. In the normal control group,cells were cultured in the basal medium for 48 hours;in the ox - LDL group,cells were treated with ox - LDL (50 mg ? L1) for 48 hours;in the ox - LDL + H2S 100 group,cells were pretreated with NaHS (100 fi,mol ? L"') for 30 minutes and then added ox - LDL (50 mg ? L"') to

  6. 新疆地区狼疮肾炎患者尿液单核细胞趋化因子1水平及临床意义%The levels of urinary monocyte chemoattractant protein 1 and clinical significance in Xinj iang patients with lupus nephritis

    Institute of Scientific and Technical Information of China (English)

    王彦焱; 赵春梅; 孟岩; 古丽仙·艾尔肯; 张新玉; 贾娜; 罗莉

    2013-01-01

    Objective To investigate urinary levels of monocyte chemoattractant protein 1(MCP-1)in Xin-jiang patients with lupus nephritis(LN),and analyze the relationship of MCP-1 with 24-hour proteinuria and 24-hour urinary albumin-to-creatinine ratio(UACR)in active lupus nephritis.Methods A cross-sec-tional cohort analysis was performed.Urinary MCP-1 levels of 33 active lupus nephritis patients and 35 in-active lupus nephritis were measured by ELISA.Results Urinary MCP-1 levels of active lupus nephritis patients were significantly higher than that of inactive lupus nephritis 468.0(205-1 990)pg/mg Cr vs 131.5 (69-734)pg/mg Cr,P=0.000).The mean age of active lupus nephritis was younger than that of inactive lupus nephritis(25.9 ± 3.7 vs 29.7 ± 3.5,P 0.05).Urinary MCP-1 was strongly correlated with 24-hour proteinuria and 24-hour UACR (r= 0.916,P=0.000 ;r=0.936,P=0.000).Conclusion Urinary MCP-1 concentration is a good biomarker for the j udgment of lupus nephritis flare and activity.Providing the Longitudinal stud-ies are warranted.%目的探讨狼疮肾炎(lupus nephritis,LN)患者尿液中单核细胞趋化因子1(monocyte chemoattractant protein 1MCP-1)的水平及其临床意义。方法采用横断面调查研究分析方法,ELISA法检测33例活动期狼疮肾炎患者和35例缓解期狼疮肾炎患者尿液中 MCP-1水平。结果活动期狼疮肾炎患者 MCP-1水平[468.0(205~1990)pg/mg Cr]明显高于缓解期狼疮肾炎患者[131.5(69~734)pg/mg Cr],差异有统计学意义(P =0.000)。活动期狼疮肾炎组患者年龄(25.9±3.7)岁,缓解期狼疮肾炎组患者年龄(29.7±3.5)岁,两组年龄有统计学差异(P <0.05),活动期狼疮肾炎组患者抗 ds-DNA抗体阳性率高于缓解期狼疮肾炎组患者(P <0.05)。两组在性别和族别上无统计学差异(P >0.05)。活动期狼疮肾炎组患者尿液中MCP-1水平与24 h尿蛋白定量及24 h

  7. Auto-chemotactic micro-swimmer suspensions: modeling, analysis and simulations

    CERN Document Server

    Lushi, Enkeleida; Shelley, Michael J

    2013-01-01

    Microorganisms can preferentially orient and move along gradients of a chemo-attractant (i.e., chemotax) while colonies of many microorganisms can collectively undergo complex dynamics in response to chemo-attractants that they themselves produce. For colonies or groups of micro-swimmers we investigate how an "auto-chemotactic" response that should lead to swimmer aggregation is affected by the non-trivial fluid flows that are generated by collective swimming. For this, we consider chemotaxis models based upon a hydrodynamic theory of motile suspensions that are fully coupled to chemo-attractant production, transport, and diffusion. Linear analysis of isotropically ordered suspensions reveals both an aggregative instability due to chemotaxis that occurs independently of swimmer type, and a hydrodynamic instability when the swimmers are "pushers". Nonlinear simulations show nonetheless that hydrodynamic interactions can significantly modify the chemotactically-driven aggregation dynamics in suspensions of "pus...

  8. An enzyme immunoassay for detection of Japanese encephalitis virus-induced chemotactic cytokine

    Indian Academy of Sciences (India)

    Aditi Singh; Rajesh Kulshreshtha; Asha Mathur

    2000-03-01

    Japanese encephalitis virus (JEV) induces human peripheral blood monocytes to secrete a chemotactic cytokine [human macrophage-derived factor (hMDF)] which causes chemotaxis of neutrophils. The only known assay for hMDF cannot quantify its level in samples, so an enzyme immunoassay has been standardized for detection of hMDF and hMDF-specific antibodies in test samples. The reported enzyme linked immunosorbent assay (ELISA) was found to be sensitive (89%), specific (91%), accurate (92·2%) and reproducible and was able to detect a minimum concentration of 23 ng hMDF/ml in test samples. The chemotactic factor could be detected in JEV inoculated mouse sera and JEV infected culture fluids. Significant finding of the test was the detection of hMDF in sera of human cases of JE.

  9. Fucose-binding Lotus tetragonolobus lectin binds to human polymorphonuclear leukocytes and induces a chemotactic response.

    Science.gov (United States)

    VanEpps, D E; Tung, K S

    1977-09-01

    Fucose-binding L. tetragonolobus lectin to the surface of human polymorphonuclear leukocytes (PMN) and induces a chemotactic response. Both surface binding and chemotaxis are inhibited by free fucose but not by fructose, mannose, or galactose. The lectin-binding sites on PMN are unrelated to the A, B, or O blood group antigen. Utilization of this lectin should be a useful tool in isolating PMN membrane components and in analyzing the mechanism of neutrophil chemotaxis. PMID:330752

  10. Study of the Chemotactic Response of Multicellular Spheroids in a Microfluidic Device

    OpenAIRE

    Jose M Ayuso; Basheer, Haneen A.; Rosa Monge; Pablo Sánchez-Álvarez; Manuel Doblaré; Shnyder, Steven D.; Victoria Vinader; Kamyar Afarinkia; Luis J Fernández; Ignacio Ochoa

    2015-01-01

    We report the first application of a microfluidic device to observe chemotactic migration in multicellular spheroids. A microfluidic device was designed comprising a central microchamber and two lateral channels through which reagents can be introduced. Multicellular spheroids were embedded in collagen and introduced to the microchamber. A gradient of fetal bovine serum (FBS) was established across the central chamber by addition of growth media containing serum into one of the lateral channe...

  11. A chemotactic model for interaction of antagonistic microflora colonies: front asymptotics and numerical simulations.

    OpenAIRE

    Málaga Iguiñiz, Carlos; Minzoni, Antonmaria Alessio; Plaza, Ramón Gabriel; Simeoni, Chiara

    2013-01-01

    International audience This paper studies a two-dimensional chemotactic model for two species in which one of them produces a chemo-repellent for the other. It is shown asymptotically and numerically how the chemical inhibits the invasion of a moving front for the second species and how stable steady states, which depend on the chemical concentration, can be reached. The results qualitatively explain experimental observations by Swain and Ray (Microbiol. Res. 164(2), 2009), where colonies ...

  12. Chemotactic model for interaction of antagonistic microflora colonies and numerical simulations

    CERN Document Server

    Malaga, Carlos; Plaza, Ramon G; Simeoni, Chiara

    2011-01-01

    This paper studies a two-dimensional chemotactic model for two species in which one of them produces a chemo-repellent for the other. Under these circumstances, the chemical inhibits the invasion of a moving front for the second species. It is shown asymptotically and numerically how stable steady states, which depend on the chemical concentration, can be reached. The results qualitatively explain experimental observations by Swain and Ray, where colonies of bacteria produce metabolite agents which prevent the invasion of fungi.

  13. Polymorphonuclear neutrophil granulocyte chemotactic hyperresponsiveness in a case of canine acromegaly.

    Science.gov (United States)

    Jensen, A L; Thomsen, M K; Aaes, H; Andreasen, M; Søndergaard, J

    1993-08-01

    Growth hormone (GH) has recently been shown to affect polymorphonuclear neutrophil granulocyte (PMN) function and to be secreted by mononuclear cells, indicating that the hormone may be active in an immunophysiologic network, acting as an endo- or paracrine priming agent. The purpose of the present study was to evaluate the chemotactic responsiveness of canine peripheral PMN in a dog with acromegaly, caused by spontaneous, progesterone-induced hypersecretion of GH and, secondary to this, a seven-fold increase in insulin-like growth factor I (IGF-I). The chemotactic responsiveness towards zymosan-activated serum (ZAS) and leukotriene B4 (LTB4) was evaluated at a time when the dog suffered from acromegaly and again 57 days after corrective surgery (ovariohysterectomy). The experiments showed that PMN from the patient exhibited enhanced chemotactic migration that appeared to be associated with the hypersomatotropic condition as judged from the reversibility of the phenomenon. The glucose intolerance and elevated serum alkaline phosphatase that were observed in the acromegalic dog were also shown to be reversible following surgery.

  14. Automated Chemotactic Sorting and Single-cell Cultivation of Microbes using Droplet Microfluidics

    Science.gov (United States)

    Dong, Libing; Chen, Dong-Wei; Liu, Shuang-Jiang; Du, Wenbin

    2016-04-01

    We report a microfluidic device for automated sorting and cultivation of chemotactic microbes from pure cultures or mixtures. The device consists of two parts: in the first part, a concentration gradient of the chemoeffector was built across the channel for inducing chemotaxis of motile cells; in the second part, chemotactic cells from the sample were separated, and mixed with culture media to form nanoliter droplets for encapsulation, cultivation, enumeration, and recovery of single cells. Chemotactic responses were assessed by imaging and statistical analysis of droplets based on Poisson distribution. An automated procedure was developed for rapid enumeration of droplets with cell growth, following with scale-up cultivation on agar plates. The performance of the device was evaluated by the chemotaxis assays of Escherichia coli (E. coli) RP437 and E. coli RP1616. Moreover, enrichment and isolation of non-labelled Comamonas testosteroni CNB-1 from its 1:10 mixture with E. coli RP437 was demonstrated. The enrichment factor reached 36.7 for CNB-1, based on its distinctive chemotaxis toward 4-hydroxybenzoic acid. We believe that this device can be widely used in chemotaxis studies without necessarily relying on fluorescent labelling, and isolation of functional microbial species from various environments.

  15. Novel Biochemical Markers of Psychosocial Stress in Women

    OpenAIRE

    Marie Asberg; Ake Nygren; Rosario Leopardi; Gunnar Rylander; Ulla Peterson; Lukas Wilczek; Håkan Källmén; Mirjam Ekstedt; Torbjörn Akerstedt; Mats Lekander; Rolf Ekman

    2009-01-01

    BACKGROUND: Prolonged psychosocial stress is a condition assessed through self-reports. Here we aimed to identify biochemical markers for screening and early intervention in women. METHODS: Plasma concentrations of interleukin (IL) 1-alpha, IL1-beta, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma (INF-gamma), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), thyroid stimulating hormone (T...

  16. Reduction of Monocyte Chemoattractant Protein-1 Expression in Rheumatoid Arthritis Rat Joints with Light-Emitting Diode Phototherapy

    OpenAIRE

    Kuboyama, Noboru; Abiko, Yoshimitsu

    2012-01-01

    Background: Rheumatoid arthritis (RA) is a systemic autoimmune disorder that involves inflammation and pain of the joints. Light-Emitting Diode (LED) irradiation is being evaluated for treating RA; however, the mechanism is unclear. Monocyte chemotaxis protein (MCP)-1 is a key chemokine in the inflammatory status of RA, and MCP-1 levels in plasma are described as a marker for joint inflammation in RA.

  17. On a competitive system under chemotactic effects with non-local terms

    International Nuclear Information System (INIS)

    In this paper, we study a system of partial differential equations describing the evolution of a population under chemotactic effects with non-local reaction terms. We consider an external application of chemoattractant in the system and study the cases of one and two populations in competition. By introducing global competitive/cooperative factors in terms of the total mass of the populations, we obtain, for a range of parameters, that any solution with positive and bounded initial data converges to a spatially homogeneous state with positive components. The proofs rely on the maximum principle for spatially homogeneous sub- and super-solutions. (paper)

  18. Effects of Garlic Oil on the Migration of Neutrophil-Like Cell Studied by Using a Chemotactic Gradient Labchip

    Directory of Open Access Journals (Sweden)

    Po-Chen Shih

    2010-01-01

    Full Text Available We have designed and fabricated a novel chemotactic gradient Labchip for studying cell migration quantitatively. Owing to the great potential of garlic and its preparations in developing antiinflammatory drugs, the aim of the present study is to investigate the effect of garlic oil on the locomotion of a neutrophil-like cell by measuring the dynamic features of cell migration including migration direction, average migration speed, chemotactic index (CI, and motility index (MI with the newly designed Labchip. We found that garlic oil treatment lowered the values of CI and MI and reduced the average speed of cell migration from 13 to 8 μm/min. The results indicate that garlic oil is a potential inhibitor for neutrophil-like cell migration and chemotactic responsiveness. By comparing with the effects of nocodazole and cytochalasin B, we also suggest that the antiinflammatory activity exhibited by garlic oil was mainly through inhibiting the assembly-disassembly processes of the cytoskeleton.

  19. Modeling of chemotactic steering of bacteria-based microrobot using a population-scale approach.

    Science.gov (United States)

    Cho, Sunghoon; Choi, Young Jin; Zheng, Shaohui; Han, Jiwon; Ko, Seong Young; Park, Jong-Oh; Park, Sukho

    2015-09-01

    The bacteria-based microrobot (Bacteriobot) is one of the most effective vehicles for drug delivery systems. The bacteriobot consists of a microbead containing therapeutic drugs and bacteria as a sensor and an actuator that can target and guide the bacteriobot to its destination. Many researchers are developing bacteria-based microrobots and establishing the model. In spite of these efforts, a motility model for bacteriobots steered by chemotaxis remains elusive. Because bacterial movement is random and should be described using a stochastic model, bacterial response to the chemo-attractant is difficult to anticipate. In this research, we used a population-scale approach to overcome the main obstacle to the stochastic motion of single bacterium. Also known as Keller-Segel's equation in chemotaxis research, the population-scale approach is not new. It is a well-designed model derived from transport theory and adaptable to any chemotaxis experiment. In addition, we have considered the self-propelled Brownian motion of the bacteriobot in order to represent its stochastic properties. From this perspective, we have proposed a new numerical modelling method combining chemotaxis and Brownian motion to create a bacteriobot model steered by chemotaxis. To obtain modeling parameters, we executed motility analyses of microbeads and bacteriobots without chemotactic steering as well as chemotactic steering analysis of the bacteriobots. The resulting proposed model shows sound agreement with experimental data with a confidence level <0.01. PMID:26487902

  20. Computational modeling of chemotactic signaling and aggregation of microglia around implantation site during deep brain stimulation

    Science.gov (United States)

    Silchenko, A. N.; Tass, P. A.

    2013-10-01

    It is well established that prolonged electrical stimulation of brain tissue causes massive release of ATP in the extracellular space. The released ATP and the products of its hydrolysis, such as ADP and adenosine, become the main elements mediating chemotactic sensitivity and motility of microglial cells via subsequent activation of P2Y2,12 as well as A3A and A2A adenosine receptors. The size of the sheath around the electrode formed by the microglial cells is an important criterion for the optimization of the parameters of electrical current delivered to brain tissue. Here, we study a purinergic signaling pathway underlying the chemotactic motion of microglia towards the implanted electrode during deep brain stimulation. We present a computational model describing formation of a stable aggregate around the implantation site due to the joint chemo-attractive action of ATP and ADP together with a mixed influence of extracellular adenosine. The model was built in accordance with the classical Keller-Segel approach and includes an equation for the cells' density as well as equations describing the hydrolysis of extracellular ATP via successive reaction steps ATP →ADP →AMP →adenosine. The results of our modeling allowed us to reveal the dependence of the width of the encapsulating layer around the electrode on the amount of ATP released due to permanent electrical stimulation. The dependences of the aggregates' size on the parameter governing the nonlinearity of interaction between extracellular adenosine and adenosine receptors are also analyzed.

  1. Spatial regulation of the cAMP-dependent protein kinase during chemotactic cell migration.

    Science.gov (United States)

    Howe, Alan K; Baldor, Linda C; Hogan, Brian P

    2005-10-01

    Historically, the cAMP-dependent protein kinase (PKA) has a paradoxical role in cell motility, having been shown to both facilitate and inhibit actin cytoskeletal dynamics and cell migration. In an effort to understand this dichotomy, we show here that PKA is regulated in subcellular space during cell migration. Immunofluorescence microscopy and biochemical enrichment of pseudopodia showed that type II regulatory subunits of PKA and PKA activity are enriched in protrusive cellular structures formed during chemotaxis. This enrichment correlates with increased phosphorylation of key cytoskeletal substrates for PKA, including the vasodilator-stimulated phosphoprotein (VASP) and the protein tyrosine phosphatase containing a PEST motif. Importantly, inhibition of PKA activity or its ability to interact with A kinase anchoring proteins inhibited the activity of the Rac GTPase within pseudopodia. This effect correlated with both decreased guanine nucleotide exchange factor activity and increased GTPase activating protein activity. Finally, inhibition of PKA anchoring, like inhibition of total PKA activity, inhibited pseudopod formation and chemotactic cell migration. These data demonstrate that spatial regulation of PKA via anchoring is an important facet of normal chemotactic cell movement.

  2. Chemotactic behavior of deep subsurface bacteria toward carbohydrates, amino acids and a chlorinated alkene

    Energy Technology Data Exchange (ETDEWEB)

    Lopez de Victoria, G. (Puerto Rico Univ., Rio Piedras (Puerto Rico). Dept. of Biology)

    1989-02-01

    The chemotactic behavior of deep terrestrial subsurface bacteria toward amino acids, carbohydrates and trichloroethylene was assayed using a modification of the capillary method and bacterial enumeration by acridine orange direct counts. Eleven isolates of bacteria isolated from six different geological formations were investigated. A bimodal response rather than an absolute positive or negative response was observed in most assays. Most of the isolates were positively chemotactic to low concentrations of substrates and were repelled by high concentrations of the same substrate. However, this was not the case for trichloroethylene (TCE) which was mostly an attractant and elicited the highest responses in all the isolates when compared with amino acids and carbohydrates. The movement rates of these isolates in aseptic subsurface sediments in the absence and presence of TCE were also determined using a laboratory model. All of the isolates showed distinct response range, peak, and threshold concentrations when exposed to the same substrates suggesting that they are possibly different species as has been inferred from DNA homology studies. 101 refs., 4 figs., 57 tabs.

  3. CONSTRUCTION OF EUKARYOTIC EXPRESSION VECTOR FOR HUMAN CCL21 AND CHARACTERIZATION OF ITS CHEMOTACTIC ACTIVITY

    Institute of Scientific and Technical Information of China (English)

    HOU Li; LIU Qi; JIAO Yu-lian; ZHANG Jie; WANG Lai-cheng; MA Chun-yan; CUI Bin; ZHANG Xue; ZHAO Yue-ran

    2006-01-01

    Objective: To obtain recombinant human CCL21 with biological activity from eukaryotic expression system for further use in cancer gene therapy. Methods: A fragment of human CCL21 gene was obtained from pSK-hCCL21 plasmid digested by Xho I and BamH I, inserted into the responding sites of eukaryotic expression vector pVAX1, and then transfected into COS-7 cells by electroporation method. The expression of hCCL21 protein was detected by western blotting analysis. The in vitro chemotaxis assay was used to test the chemotactic function of the expression product to lymphocytes. Results: Human CCL21 protein was expressed by transfected COS-7 cells with recombinant plasmid containing hCCL21 gene, and was verified by western blotting. The in vitro chemotaxis assay demonstrated that human CCL21 protein had a potent chemotactic function to lymphocytes. Conclusion: Human CCL21 was successfully and transiently expressed in eukaryotic cells, which lays some foundation for the study of CCL21 gene therapy in murine tumor models.

  4. A model for cell type localization in the migrating slug of Dictyostelium discoideum based on differential chemotactic sensitivity to cAMP and differential sensitivity to suppression of chemotaxis by ammonia

    Indian Academy of Sciences (India)

    Ira N Feit; Jeffrey Pawlikowski; Caroline Zawilski

    2007-03-01

    The three basic cell types in the migrating slug of Dictyostelium discoideum show differential chemotactic response to cyclic AMP (cAMP) and differential sensitivity to suppression of the chemotaxis by ammonia. The values of these parameters indicate a progressive maturation of chemotactic properties during the transdifferentiation of slug cell types. We present a model that explains the localization of the three cell types within the slug based on these chemotactic differences and on the maturation of their chemotactic properties.

  5. NANOPARTICLE AS A NEW GENE TRANSFERRING VECTOR IN SPECIFIC EXPRESSION GENE

    Institute of Scientific and Technical Information of China (English)

    管珩; 李拥军; 郑曰宏; 刘昌伟; 杨菁; 宋存先; 王彭延; 赵三妹; 王宗立; 佘铭鹏

    2002-01-01

    Objective. To evaluate the possibility and efficiency of nanoparticle as a new vector in specific gene transference.Methods. Nanoparticle-DNA complex was prepared with Poly- dl-lactic-co-glycolic acid (PLGA) beating antisense monocyte chemotactic protein-1 (A-MCP-1), a specific expression gene, and the package efficiency, release progress in vitro, and the size of the complex were determined. The possibility of the new vector was evaluated with genomic DNA PCR by transferring gene into cultured smooth muscle cells (SMC), cationic lipids as a control. For study in vivo, jugular vein-to-artery bypass grafting procedures were performed on 20 New Zealand white rabbits, of which 6 grafts were transferred with nanoparticle-A-MCP-1 (200 μg), 6 with A - MCP - 1(200 μ g) by cationic liposome, 4 with LNCX plasmid, and 4 as control. Fourteen days after the grafts were harvested, the expression of A-MCP-1 and its effect on MCP-1 in vein grafts were detected by dot blot, and the morphologic evaluation of grafts was performed.Results. The package efficiency of the nanoparticle-DNA complex was 0. 9%, release progress in vitro lasted 2 weeks, and the size ranged from 150 to 300nm. SMC genomic DNA PCR showed that A-MCP-1 gene could be successfully transfected into cells by nanoparticle. The study in vivo indicated that A-MCP-1 mRNA was expressed in both local gene delivery groups, nanoparticle and liposome, meanwhile, MCP-1 expression in vein grafts was significantly inhibited and neointimal hyperplasia was notably reduced.Conclusion. Nanoparticle can act as a vector to transfect specific gene.

  6. Boc SPPS of two hydrophobic peptides using a ''solubilising tail'' strategy : Dodecaalanine and chemotactic protein 10(42-55)

    NARCIS (Netherlands)

    Englebretsen, DR; Alewood, PF

    1996-01-01

    The solid phase syntheses of the hydrophobic peptides dodecaalanine and chemotactic protein-10(42-55) were achieved using a ''solubilising tail'' strategy. Peptide constructs of the form H-hydrophobic peptide-glycolamide ester-(Gly-Arg)(4)-Gly-OH were synthesised by Boc SPPS. The peptide-constructs

  7. How many consumer levels can survive in a chemotactic food chain?

    Institute of Scientific and Technical Information of China (English)

    Jing LIU; Chunhua OU

    2009-01-01

    We investigate the effect and the impact of predator-prey interactions, diffusivity and chemotaxis on the ability of survival of multiple consumer levels in a predator-prey microbial food chain. We aim at answering the question of how many consumer levels can survive from a dynamical system point of view. To solve this standing issue on food-chain length, first we construct a chemotactic food chain model. A priori bounds of the steady state populations are obtained. Then under certain sufficient conditions combining the effect of conversion efficiency, diffusivity and chemotaxis parameters, we derive the co-survival of all consumer levels, thus obtaining the food chain length of our model. Numerical simulations not only confirm our theoretical results, but also demonstrate the impact of conversion efficiency, diffusivity and chemotaxis behavior on the survival and stability of various consumer levels.

  8. Study of the Chemotactic Response of Multicellular Spheroids in a Microfluidic Device.

    Directory of Open Access Journals (Sweden)

    Jose M Ayuso

    Full Text Available We report the first application of a microfluidic device to observe chemotactic migration in multicellular spheroids. A microfluidic device was designed comprising a central microchamber and two lateral channels through which reagents can be introduced. Multicellular spheroids were embedded in collagen and introduced to the microchamber. A gradient of fetal bovine serum (FBS was established across the central chamber by addition of growth media containing serum into one of the lateral channels. We observe that spheroids of oral squamous carcinoma cells OSC-19 invade collectively in the direction of the gradient of FBS. This invasion is more directional and aggressive than that observed for individual cells in the same experimental setup. In contrast to spheroids of OSC-19, U87-MG multicellular spheroids migrate as individual cells. A study of the exposure of spheroids to the chemoattractant shows that the rate of diffusion into the spheroid is slow and thus, the chemoattractant wave engulfs the spheroid before diffusing through it.

  9. Study of the Chemotactic Response of Multicellular Spheroids in a Microfluidic Device.

    Science.gov (United States)

    Ayuso, Jose M; Basheer, Haneen A; Monge, Rosa; Sánchez-Álvarez, Pablo; Doblaré, Manuel; Shnyder, Steven D; Vinader, Victoria; Afarinkia, Kamyar; Fernández, Luis J; Ochoa, Ignacio

    2015-01-01

    We report the first application of a microfluidic device to observe chemotactic migration in multicellular spheroids. A microfluidic device was designed comprising a central microchamber and two lateral channels through which reagents can be introduced. Multicellular spheroids were embedded in collagen and introduced to the microchamber. A gradient of fetal bovine serum (FBS) was established across the central chamber by addition of growth media containing serum into one of the lateral channels. We observe that spheroids of oral squamous carcinoma cells OSC-19 invade collectively in the direction of the gradient of FBS. This invasion is more directional and aggressive than that observed for individual cells in the same experimental setup. In contrast to spheroids of OSC-19, U87-MG multicellular spheroids migrate as individual cells. A study of the exposure of spheroids to the chemoattractant shows that the rate of diffusion into the spheroid is slow and thus, the chemoattractant wave engulfs the spheroid before diffusing through it. PMID:26444904

  10. Study of the Chemotactic Response of Multicellular Spheroids in a Microfluidic Device

    Science.gov (United States)

    Ayuso, Jose M.; Basheer, Haneen A.; Monge, Rosa; Sánchez-Álvarez, Pablo; Doblaré, Manuel; Shnyder, Steven D.; Vinader, Victoria; Afarinkia, Kamyar

    2015-01-01

    We report the first application of a microfluidic device to observe chemotactic migration in multicellular spheroids. A microfluidic device was designed comprising a central microchamber and two lateral channels through which reagents can be introduced. Multicellular spheroids were embedded in collagen and introduced to the microchamber. A gradient of fetal bovine serum (FBS) was established across the central chamber by addition of growth media containing serum into one of the lateral channels. We observe that spheroids of oral squamous carcinoma cells OSC–19 invade collectively in the direction of the gradient of FBS. This invasion is more directional and aggressive than that observed for individual cells in the same experimental setup. In contrast to spheroids of OSC–19, U87-MG multicellular spheroids migrate as individual cells. A study of the exposure of spheroids to the chemoattractant shows that the rate of diffusion into the spheroid is slow and thus, the chemoattractant wave engulfs the spheroid before diffusing through it. PMID:26444904

  11. Biodegradation of naphthalene and anthracene by chemo-tactically active rhizobacteria of populus deltoides

    Directory of Open Access Journals (Sweden)

    Sandeep Bisht

    2010-12-01

    Full Text Available Several naphthalene and anthracene degrading bacteria were isolated from rhizosphere of Populus deltoides, which were growing in non-contaminated soil. Among these, four isolates, i.e. Kurthia sp., Micrococcus varians, Deinococcus radiodurans and Bacillus circulans utilized chrysene, benzene, toluene and xylene, in addition to anthracene and naphthalene. Kurthia sp and B. circulans showed positive chemotactic response for naphthalene and anthracene. The mean growth rate constant (K of isolates were found to increase with successive increase in substrate concentration (0.5 to 1.0 mg/50ml. B. circulans SBA12 and Kurthia SBA4 degraded 87.5% and 86.6% of anthracene while, Kurthia sp. SBA4, B. circulans SBA12, and M. varians SBA8 degraded 85.3 %, 95.8 % and 86.8 % of naphthalene respectively after 6 days of incubation as determined by HPLC analysis.

  12. Expression and divalent cation binding properties of the novel chemotactic inflammatory protein psoriasin

    DEFF Research Database (Denmark)

    Vorum, H; Madsen, Peder; Rasmussen, H H;

    1996-01-01

    Psoriasin is a novel chemotactic inflammatory protein that possesses weak similarity to the S100 family members of Ca(2+)-binding proteins, and that is highly up-regulated in hyperproliferative psoriatic keratinocytes. Here we have used the psoriasin cDNA to express recombinant human (rh) psoriasin...... in Escherichia coli as a fusion protein containing a hexa His tag and a factor Xa cleavage site in the NH2-terminus. The protein was purified by affinity chromatography on Ni(2+)-nitrilotriacetic acid agarose, digested with factor Xa, further purified by ion-exchange chromatography and characterized by two...... in KCl and four in NaCl, with an affinity just below 1 x 10(4) M-1 for the first molecule. Thus psoriasin does not bind significant amounts of Zn2+ at physiological concentrations. Mg2+ and Ca2+ are bound anti-cooperatively and binding of each of the ions (Ca2+, Zn2+, or Mg2+), is accompanied...

  13. Loss-of-function mutations in Rab escort protein 1 (REP-1 affect intracellular transport in fibroblasts and monocytes of choroideremia patients.

    Directory of Open Access Journals (Sweden)

    Natalia V Strunnikova

    Full Text Available BACKGROUND: Choroideremia (CHM is a progressive X-linked retinopathy caused by mutations in the CHM gene, which encodes Rab escort protein-1 (REP-1, an escort protein involved in the prenylation of Rabs. Under-prenylation of certain Rabs, as a result of loss of function mutations in REP-1, could affect vesicular trafficking, exocytosis and secretion in peripheral cells of CHM patients. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate this hypothesis, intracellular vesicle transport, lysosomal acidification and rates of proteolytic degradation were studied in monocytes (CD14+ fraction and primary skin fibroblasts from the nine age-matched controls and thirteen CHM patients carrying 10 different loss-of-function mutations. With the use of pHrodo BioParticles conjugated with E. coli, collagen I coated FluoSpheres beads and fluorescent DQ ovalbumin with BODYPY FL dye, we demonstrated for the first time that lysosomal pH was increased in monocytes of CHM patients and, as a consequence, the rates of proteolytic degradation were slowed. Microarray analysis of gene expression revealed that some genes involved in the immune response, small GTPase regulation, transcription, cell adhesion and the regulation of exocytosis were significantly up and down regulated in cells from CHM patients compared to controls. Finally, CHM fibroblasts secreted significantly lower levels of cytokine/growth factors such as macrophage chemoattractant protein-1 (MCP-1, pigment epithelial derived factor (PEDF, tumor necrosis factor (TNF alpha, fibroblast growth factor (FGF beta and interleukin (lL-8. CONCLUSIONS/SIGNIFICANCE: We demonstrated for the first time that peripheral cells of CHM patients had increased pH levels in lysosomes, reduced rates of proteolytic degradation and altered secretion of cytokines. Peripheral cells from CHM patients expose characteristics that were not previously recognized and could used as an alternative models to study the effects of different

  14. Alcohol modulates circulating levels of interleukin-6 and monocyte chemoattractant protein-1 in chronic pancreatitis

    DEFF Research Database (Denmark)

    Pedersen, N; Larsen, S; Seidelin, J B;

    2004-01-01

    Cytokines are markers of acute pancreatic inflammation and essential for distant organ injury, but they also stimulate pancreatic fibrogenesis and are thus involved in the progression from acute pancreatitis to chronic pancreatic injury and fibrosis. The aim of this study was to evaluate the...... circulating levels of IL-6, MCP-1, TGF-beta1, IGF-1 and IGFBP-3 in patients with alcoholic chronic pancreatitis (CP)....

  15. Alcohol modulates circulating levels of interleukin-6 and monocyte chemoattractant protein-1 in chronic pancreatitis

    DEFF Research Database (Denmark)

    Pedersen, N; Larsen, S; Seidelin, J B;

    2004-01-01

    Cytokines are markers of acute pancreatic inflammation and essential for distant organ injury, but they also stimulate pancreatic fibrogenesis and are thus involved in the progression from acute pancreatitis to chronic pancreatic injury and fibrosis. The aim of this study was to evaluate...... the circulating levels of IL-6, MCP-1, TGF-beta1, IGF-1 and IGFBP-3 in patients with alcoholic chronic pancreatitis (CP)....

  16. [Macrophages promote the migration of neural stem cells into mouse spinal cord injury site].

    Science.gov (United States)

    Cheng, Zhijian; Zhu, Wen; Li, Haopeng; He, Xijing

    2016-09-01

    Objective To explore the role of macrophages in the migration of neural stem cells (NSCs) in vivo and in vitro . Methods NSCs with green fluorescent protein (GFP) were isolated from GFP transgenic mice and the immunofluorescence cytochemical staining of nestin was used to identify NSCs. After spinal cord injury was induced, the tissue level of macrophage chemotactic protein-1 (MCP-1) mRNA was detected using quantitative real time PCR. The migration of GFP-NSCs was investigated 1 week after GFP-NSCs were injected into both sides of the damaged area. The effect of macrophage on the migration of NSCs in vitro was tested by Transwell(TM) system and the content of MCP-1 was detected by ELISA. Results NSCs highly expressed nestin. Compared with the control group, the level of MCP-1 mRNA significantly increased in the spinal cord injury group. The NSCs which were injected into the spinal cord migrated into the center of the injured site where F4/80 was highly expressed. Macrophages significantly increased the number of migrating NSCs in vitro and the secretion of MCP-1. Conclusion Macrophages induce NSC migrating into the spinal cord injury site possibly through promoting the secretion of MCP-1. PMID:27609570

  17. Direct and indirect radioiodination of protein: comparative study of chemotactic peptide labeling

    International Nuclear Information System (INIS)

    The development of simple methods for protein radioiodination have stimulated the use of radioiodinated peptides in vivo. There are two basic methods for labeling proteins with radioiodine: direct labeling, reaction of an electrophilic radioiodine with functional activated groups on protein, like the phenol ring in the tyrosine residue, and the conjugation of a previously radioiodinated molecule to the protein, referred as indirect method. The great problem related to the direct radioiodination of proteins is the in vivo dehalogenation. This problem can be minimized if a non-phenolic prosthetic group is used in the indirect radioiodination of the peptide. The ATE prosthetic group, N-succinimidyl 3-(tri-n-butylstannyl) benzoate, when radioiodinated by electrophilic iododestannilation produces N-succinimidyl 3-[123l/131l] iodine benzoate (SIB) that is subsequently conjugated to the protein by the acylation of the lysine group. There are many radiopharmaceuticals employed in scintigraphic images of infection and inflammation used with some limitations. These limitations stimulated the improvement of a new class of radiopharmaceuticals, the receptor-specific related labeled peptides, as the mediators of the inflammatory response, that presents high affinity by receptors expressed in the inflammation process, and fast clearance from blood and non-target tissues. One of these molecules is the synthetic chemotactic peptide fNleLFNIeYK that presents potent chemotaxis for leukocytes, with high affinity by the receptors presented in polymorphonuclear leukocytes and mononuclear phagocytes. The objective of this work included the synthesis of ATE prosthetic group and comparative radioiodination of the chemotactic peptide fNleLFNIeYK by direct and indirect methods, with radiochemical purity determination and evaluation of in vivo and in vitro stability of the compounds. This work presented an original contribution in the comparative biological distribution studies of the

  18. Down-regulation of the chemokine receptor CCR5 by activation of chemotactic formyl peptide receptor in human monocytes.

    Science.gov (United States)

    Shen, W; Li, B; Wetzel, M A; Rogers, T J; Henderson, E E; Su, S B; Gong, W; Le, Y; Sargeant, R; Dimitrov, D S; Oppenheim, J J; Wang, J M

    2000-10-15

    Interactions between cell surface receptors are important regulatory elements in the complex host responses to infections. In this study, it is shown that a classic chemotactic factor, the bacterial chemotactic peptide N-formyl-methionyl-leucylphenyl-alanine (fMLF), rapidly induced a protein-kinase-C-mediated serine phosphorylation and down-regulation of the chemokine receptor CCR5, which serves as a major human immunodeficiency virus (HIV)-1 coreceptor. The fMLF binding to its receptor, formyl peptide receptor (FPR), resulted in significant attenuation of cell responses to CCR5 ligands and in inhibition of HIV-1-envelope-glycoprotein-mediated fusion and infection of cells expressing CD4, CCR5, and FPR. The finding that the expression and function of CCR5 can be regulated by peptides that use an unrelated receptor may provide a novel approach to the design of anti-inflamatory and antiretroviral agents. (Blood. 2000;96:2887-2894)

  19. Production of interleukin 8 and Monocyte chemoattractant protein-1 on human umbilical vein endothelial cells stimulated by Porphyromonas gingivalis with different fimA genotypes

    Institute of Scientific and Technical Information of China (English)

    Shu-Yu Cai; Song Ge

    2015-01-01

    Objective:To study the effects ofPorphyromonas gingivalis (Pg) with different fimA genotypes on IL-8 and MCP-1 produciton by human umbilical vein endothelial cells and to reveal their the possible role in the development of atherosclerosis.Methods: Pg with different fimA genotypes were cultured with anaerobic and were used to infect HUVEC cells at a MOI of 100. Supernatant IL-8 and MCP-1 contents of cultured HUVEC cells after Pg stimulation at 2 h, 6 h and 24 h, respectively, were detected by ELISA.Results: Supernatant IL-8 and MCP-1 contents of HUVEC cells after Pg stimulation at 2 h, 6 h and 24 h were significantly higher than those in un-stimulation groups (P<0.05), and supernatant IL-8 and MCP-1 contents of HUVEC cells after II fimA and IV fimA genotypes Pg stimulation were significantly higher than those after I fimA genotypes Pg stimulation (P<0.05). Also, supernatant IL-8 and MCP-1 contents of HUVEC cells after II fimA genotypes Pg stimulation were significantly higher than those after IV fimA genotypes Pg stimulation.Conclusion: Pg with II fimA genotypes show a stronger ability to stimulate HUVEC cells to express IL-8 and MCP-1,which may lead a functional disorder of vascular endothelial.

  20. Modification of β-Defensin-2 by Dicarbonyls Methylglyoxal and Glyoxal Inhibits Antibacterial and Chemotactic Function In Vitro.

    Directory of Open Access Journals (Sweden)

    Janna G Kiselar

    Full Text Available Beta-defensins (hBDs provide antimicrobial and chemotactic defense against bacterial, viral and fungal infections. Human β-defensin-2 (hBD-2 acts against gram-negative bacteria and chemoattracts immature dendritic cells, thus regulating innate and adaptive immunity. Immunosuppression due to hyperglycemia underlies chronic infection in Type 2 diabetes. Hyperglycemia also elevates production of dicarbonyls methylgloxal (MGO and glyoxal (GO.The effect of dicarbonyl on defensin peptide structure was tested by exposing recombinant hBD-2 (rhBD-2 to MGO or GO with subsequent analysis by MALDI-TOF MS and LC/MS/MS. Antimicrobial function of untreated rhBD-2 vs. rhBD-2 exposed to dicarbonyl against strains of both gram-negative and gram-positive bacteria in culture was determined by radial diffusion assay. The effect of dicarbonyl on rhBD-2 chemotactic function was determined by chemotaxis assay in CEM-SS cells.MGO or GO in vitro irreversibly adducts to the rhBD-2 peptide, and significantly reduces antimicrobial and chemotactic functions. Adducts derive from two arginine residues, Arg22 and Arg23 near the C-terminus, and the N-terminal glycine (Gly1. We show by radial diffusion testing on gram-negative E. coli and P. aeruginosa, and gram-positive S. aureus, and a chemotaxis assay for CEM-SS cells, that antimicrobial activity and chemotactic function of rhBD-2 are significantly reduced by MGO.Dicarbonyl modification of cationic antimicrobial peptides represents a potential link between hyperglycemia and the clinical manifestation of increased susceptibility to infection, protracted wound healing, and chronic inflammation in undiagnosed and uncontrolled Type 2 diabetes.

  1. Comamonas testosteroni uses a chemoreceptor for tricarboxylic acid cycle intermediates to trigger chemotactic responses towards aromatic compounds.

    Science.gov (United States)

    Ni, Bin; Huang, Zhou; Fan, Zheng; Jiang, Cheng-Ying; Liu, Shuang-Jiang

    2013-11-01

    Bacterial chemotaxis towards aromatic compounds has been frequently observed; however, knowledge of how bacteria sense aromatic compounds is limited. Comamonas testosteroni CNB-1 is able to grow on a range of aromatic compounds. This study investigated the chemotactic responses of CNB-1 to 10 aromatic compounds. We constructed a chemoreceptor-free, non-chemotactic mutant, CNB-1Δ20, by disruption of all 19 putative methyl-accepting chemotaxis proteins (MCPs) and the atypical chemoreceptor in strain CNB-1. Individual complementation revealed that a putative MCP (tagged MCP2201) was involved in triggering chemotaxis towards all 10 aromatic compounds. The recombinant sensory domain of MCP2201 did not bind to 3- or 4-hydroxybenzoate, protocatechuate, catechol, benzoate, vanillate and gentisate, but bound oxaloacetate, citrate, cis-aconitate, isocitrate, α-ketoglutarate, succinate, fumarate and malate. The mutant CNB-1ΔpmdF that lost the ability to metabolize 4-hydroxybenzoate and protocatechuate also lost its chemotactic response to these compounds, suggesting that taxis towards aromatic compounds is metabolism-dependent. Based on the ligand profile, we proposed that MCP2201 triggers taxis towards aromatic compounds by sensing TCA cycle intermediates. Our hypothesis was further supported by the finding that introduction of the previously characterized pseudomonad chemoreceptor (McpS) for TCA cycle intermediates into CNB-1Δ20 likewise triggered chemotaxis towards aromatic compounds.

  2. A Worldwide Competition to Compare the Speed and Chemotactic Accuracy of Neutrophil-Like Cells

    Science.gov (United States)

    Wong, Elisabeth; Hamza, Bashar; Bae, Albert; Martel, Joseph; Kataria, Rama; Keizer-Gunnink, Ineke; Kortholt, Arjan; Van Haastert, Peter J. M.; Charras, Guillaume; Janetopoulos, Christopher; Irimia, Daniel

    2016-01-01

    Chemotaxis is the ability to migrate towards the source of chemical gradients. It underlies the ability of neutrophils and other immune cells to hone in on their targets and defend against invading pathogens. Given the importance of neutrophil migration to health and disease, it is crucial to understand the basic mechanisms controlling chemotaxis so that strategies can be developed to modulate cell migration in clinical settings. Because of the complexity of human genetics, Dictyostelium and HL60 cells have long served as models system for studying chemotaxis. Since many of our current insights into chemotaxis have been gained from these two model systems, we decided to compare them side by side in a set of winner-take-all races, the Dicty World Races. These worldwide competitions challenge researchers to genetically engineer and pharmacologically enhance the model systems to compete in microfluidic racecourses. These races bring together technological innovations in genetic engineering and precision measurement of cell motility. Fourteen teams participated in the inaugural Dicty World Race 2014 and contributed cell lines, which they tuned for enhanced speed and chemotactic accuracy. The race enabled large-scale analyses of chemotaxis in complex environments and revealed an intriguing balance of speed and accuracy of the model cell lines. The successes of the first race validated the concept of using fun-spirited competition to gain insights into the complex mechanisms controlling chemotaxis, while the challenges of the first race will guide further technological development and planning of future events. PMID:27332963

  3. A Worldwide Competition to Compare the Speed and Chemotactic Accuracy of Neutrophil-Like Cells.

    Science.gov (United States)

    Skoge, Monica; Wong, Elisabeth; Hamza, Bashar; Bae, Albert; Martel, Joseph; Kataria, Rama; Keizer-Gunnink, Ineke; Kortholt, Arjan; Van Haastert, Peter J M; Charras, Guillaume; Janetopoulos, Christopher; Irimia, Daniel

    2016-01-01

    Chemotaxis is the ability to migrate towards the source of chemical gradients. It underlies the ability of neutrophils and other immune cells to hone in on their targets and defend against invading pathogens. Given the importance of neutrophil migration to health and disease, it is crucial to understand the basic mechanisms controlling chemotaxis so that strategies can be developed to modulate cell migration in clinical settings. Because of the complexity of human genetics, Dictyostelium and HL60 cells have long served as models system for studying chemotaxis. Since many of our current insights into chemotaxis have been gained from these two model systems, we decided to compare them side by side in a set of winner-take-all races, the Dicty World Races. These worldwide competitions challenge researchers to genetically engineer and pharmacologically enhance the model systems to compete in microfluidic racecourses. These races bring together technological innovations in genetic engineering and precision measurement of cell motility. Fourteen teams participated in the inaugural Dicty World Race 2014 and contributed cell lines, which they tuned for enhanced speed and chemotactic accuracy. The race enabled large-scale analyses of chemotaxis in complex environments and revealed an intriguing balance of speed and accuracy of the model cell lines. The successes of the first race validated the concept of using fun-spirited competition to gain insights into the complex mechanisms controlling chemotaxis, while the challenges of the first race will guide further technological development and planning of future events. PMID:27332963

  4. Hydrocarbon biodegradation and dynamic laser speckle for detecting chemotactic responses at low bacterial concentration

    Institute of Scientific and Technical Information of China (English)

    Melina Nisenbaum; Gonzalo Hernán Sendra; Gastón Alfredo Cerdá Gilbert; Marcelo Scagliola; Jorge Froilán González; Silvia Elena Murialdo

    2013-01-01

    We report on the biodegradation of pure hydrocarbons and chemotaxis towards these compounds by an isolated chlorophenol degrader,Pseudomonas strain H.The biochemical and phylogenetic analysis of the 16S rDNA sequence identified Pseudomonas strain H as having 99.56% similarity with P.aeruginosa PA01.This strain was able to degrade n-hexadecane,1-undecene,1-nonene,1-decene,1-dodecene and kerosene.It grew in the presence of 1-octene,while this hydrocarbons is toxic to other hydrocarbons degraders.Pseudomonas strain H was also chemotactic towards n-hexadecane,kerosene,1-undecene and 1-dodecene.These results show that this Pseudomonas strain H is an attractive candidate for hydrocarbon-containing wastewater bioremediation in controlled environments.Since the classical standard techniques for detecting chemotaxis are not efficient at low bacterial concentrations,we demonstrate the use of the dynamic speckle laser method,which is simple and inexpensive,to confirm bacterial chemotaxis at low cell concentrations (less than 105 colony-forming unit per millilitre (CFU/mL)) when hydrocarbons are the attractants.

  5. Enhancement of Chemotactic Cell Aggregation by Haptotactic Cell-To-Cell Interaction.

    Directory of Open Access Journals (Sweden)

    Tae-Goo Kwon

    Full Text Available The crawling of biological cell is a complex phenomenon involving various biochemical and mechanical processes. Some of these processes are intrinsic to individual cells, while others pertain to cell-to-cell interactions and to their responses to extrinsically imposed cues. Here, we report an interesting aggregation dynamics of mathematical model cells, when they perform chemotaxis in response to an externally imposed global chemical gradient while they influence each other through a haptotaxis-mediated social interaction, which confers intriguing trail patterns. In the absence of the cell-to-cell interaction, the equilibrium population density profile fits well to that of a simple Keller-Segal population dynamic model, in which a chemotactic current density [Formula: see text] competes with a normal diffusive current density [Formula: see text], where p and ρ refer to the concentration of chemoattractant and population density, respectively. We find that the cell-to-cell interaction confers a far more compact aggregation resulting in a much higher peak equilibrium cell density. The mathematical model system is applicable to many biological systems such as swarming microglia and neutrophils or accumulating ants towards a localized food source.

  6. Influence of corticosteroids on chemotactic response and collagen metabolism of human skin fibroblasts.

    Science.gov (United States)

    Hein, R; Mauch, C; Hatamochi, A; Krieg, T

    1988-07-15

    Following chronic administration of corticosteroids in vivo, a number of complications occur, which mainly involve the metabolism of connective tissue cells. Therefore, several attempts have been made to develop corticosteroids, which show less pronounced side effects. Fibroblasts were kept in monolayer cultures and were exposed to corticosteroids demonstrating similar anti-inflammatory activity (prednicarbate, desoximetasone). Chemotaxis of fibroblasts was studied over 4 hr, protein and collagen synthesis were estimated using proteinchemical methods and also by dot blot hybridization. Corticosteroids used in a high dosage (10 microM) affected all biosynthetic capacities of the investigated fibroblasts. Protein synthesis and production of collagen types I and III were reduced and a similar decrease of mRNA levels for collagen type I could be found indicating an influence on the pretranslational control. In the same concentrations desoximetasone was much more active than prednicarbate. Fibroblast migration was dosage dependently inhibited from 10(-9) M to 10(-5) M for desoximetasone, while incubation with prednicarbate did not cause a reduction of the chemotactic response at concentrations lower than 10(-7) M. These data suggest that modifications of corticosteroids might result in a dissociation of some of their biological activities and can specifically influence their effects on biosynthetic capacities of fibroblasts. PMID:3395353

  7. Marangoni-driven chemotaxis, chemotactic collapse, and the Keller-Segel equation

    Science.gov (United States)

    Shelley, Michael; Masoud, Hassan

    2013-11-01

    Almost by definition, chemotaxis involves the biased motion of motile particles along gradients of a chemical concentration field. Perhaps the most famous model for collective chemotaxis in mathematical biology is the Keller-Segel model, conceived to describe collective aggregation of slime mold colonies in response to an intrinsically produced, and diffusing, chemo-attractant. Heavily studied, particularly in 2D where the system is ``super-critical'', it has been proved that the KS model can develop finite-time singularities - so-called chemotactic collapse - of delta-function type. Here, we study the collective dynamics of immotile particles bound to a 2D interface above a 3D fluid. These particles are chemically active and produce a diffusing field that creates surface-tension gradients along the surface. The resultant Marangoni stresses create flows that carry the particles, possibly concentrating them. Remarkably, we show that this system involving 3D diffusion and fluid dynamics, exactly yields the 2D Keller-Segel model for the surface-flow of active particles. We discuss the consequences of collapse on the 3D fluid dynamics, and generalizations of the fluid-dynamical model.

  8. Wave Patterns in Cell Membrane and Actin Cortex Uncoupled from Chemotactic Signals.

    Science.gov (United States)

    Gerisch, Günther; Ecke, Mary

    2016-01-01

    When cells of Dictyostelium discoideum orientate in a gradient of chemoattractant, they are polarized into a protruding front pointing toward the source of attractant, and into a retracting tail. Under the control of chemotactic signal inputs, Ras is activated and PIP3 is synthesized at the front, while the PIP3-degrading phosphatase PTEN decorates the tail region. As a result of signal transduction, actin filaments assemble at the front into dendritic structures associated with the Arp2/3 complex, in contrast to the tail region where a loose actin meshwork is associated with myosin-II and cortexillin, an antiparallel actin-bundling protein. In axenically growing strains of D. discoideum, wave patterns built by the same components evolve in the absence of any external signal input. Since these autonomously generated patterns are constrained to the plane of the substrate-attached cell surface, they are optimally suited to the optical analysis of state transitions between front-like and tail-like states of the membrane and the actin cortex. Here, we describe imaging techniques using fluorescent proteins to probe for the state of the membrane, the reorganization of the actin network, and the dynamics of wave patterns.

  9. Anti-coreceptor therapy drives selective T cell egress by suppressing inflammation-dependent chemotactic cues

    Science.gov (United States)

    Martin, Aaron J.; Clark, Matthew; Gojanovich, Gregory; Manzoor, Fatima; Miller, Keith; Kline, Douglas E.; Morillon, Y. Maurice; Wang, Bo

    2016-01-01

    There continues to be a need for immunotherapies to treat type 1 diabetes in the clinic. We previously reported that nondepleting anti-CD4 and -CD8 Ab treatment effectively reverses diabetes in new-onset NOD mice. A key feature of the induction of remission is the egress of the majority of islet-resident T cells. How this occurs is undefined. Herein, the effects of coreceptor therapy on islet T cell retention were investigated. Bivalent Ab binding to CD4 and CD8 blocked TCR signaling and T cell cytokine production, while indirectly downregulating islet chemokine expression. These processes were required for T cell retention, as ectopic IFN-γ or CXCL10 inhibited Ab-mediated T cell purging. Importantly, treatment of humanized mice with nondepleting anti–human CD4 and CD8 Ab similarly reduced tissue-infiltrating human CD4+ and CD8+ T cells. These findings demonstrate that Ab binding of CD4 and CD8 interrupts a feed-forward circuit by suppressing T cell–produced cytokines needed for expression of chemotactic cues, leading to rapid T cell egress from the islets. Coreceptor therapy therefore offers a robust approach to suppress T cell–mediated pathology by purging T cells in an inflammation-dependent manner.

  10. Urinary monocyte chemoattractant protein-1 and hepcidin and early diabetic nephropathy lesions in type 1 diabetes mellitus

    OpenAIRE

    Fufaa, Gudeta D.; Weil, E. Jennifer; Nelson, Robert G; Hanson, Robert L.; Knowler, William C.; Rovin, Brad H; Wu, Haifeng; Jon B Klein; Mifflin, Theodore E.; Feldman, Harold I.; Vasan, Ramachandran S.; Kimmel, Paul L.; Kusek, John W.; Mauer, Michael; Zinman, Bernard

    2015-01-01

    …the residual risk of renal disease progression in patients with diabetic nephropathy is still extremely high despite current optimal treatment; innate immunity, MCP-1 and macrophage tissue infiltration seem very promising targets for future treatment of diabetic nephropathy on top of the standard of care with RAAS inhibition.

  11. Dietary Antioxidants Decrease Serum Soluble Adhesion Molecule (sVCAM-1, sICAM-1 but not Chemokine (JE/MCP-1, KC Concentrations, and Reduce Atherosclerosis in C57BL but Not ApoE*3 Leiden Mice Fed an Atherogenic Diet

    Directory of Open Access Journals (Sweden)

    Nuala Murphy

    2005-01-01

    Full Text Available Dietary antioxidants are reported to suppress cellular expression of chemokines and adhesion molecules that recruit monocytes to the artery wall during atherosclerosis. In the present study we measured the effect of feeding apoE*3 Leiden mice or their non-transgenic (C57BL littermates with atherogenic diets either deficient in, or supplemented with, dietary antioxidants (vitamin E, vitamin C and β-carotene for 12 weeks, on serum levels of CC (JE/MCP-1 and CXC (KC chemokines and soluble adhesion molecules (sVCAM-1, sICAM-1 and atherosclerotic lesion size. ApoE*3 Leiden mice developed gross hypercholesterolaemia, and markedly accelerated (10–20 fold; P < 0.0001 atherogenesis, compared with non-transgenic animals. Antioxidant consumption reduced lesion area in non-transgenic, but not apoE*3 Leiden, mice. Serum sVCAM-1 and sICAM-1 levels were significantly (P < 0.0001 increased (sVCAM-1 up to 3.9 fold; sICAM-1 up to 2.4 fold by 4—8 weeks in all groups, and then declined. The initial increase in the concentration of adhesion molecules was reduced by 38%— 61% (P < 0.05 by antioxidant consumption, particularly in non-transgenic mice. By contrast, serum chemokine levels tended to increase more rapidly from baseline in apoE*3 Leiden mice, compared with non-transgenic animals, but were unaffected by dietary antioxidants. We conclude that dietary antioxidants reduce circulating soluble adhesion molecules and atherosclerosis in C57BL mice.

  12. Enterohepatic circulation of bacterial chemotactic peptide in rats with experimental colitis

    International Nuclear Information System (INIS)

    The association of hepatobiliary disorders with colonic inflammation is well recognized. Although the pathophysiology is obscure, increased permeation of toxic bacterial products across the inflamed gut to the portal circulation might be one mechanism. Potentially toxic metabolites include N-formylated chemotactic peptides that are produced by several species of intestinal bacteria and can be detected in colonic fluid in vivo. To investigate the metabolic fate of one of these low molecular weight proinflammatory peptides, N-formyl L-methionine L-leucine 125I-L-tyrosine was introduced into colon loops of healthy rats (n = 10) and rats with experimental colitis (n = 15) induced by rectal instillation of 15% (vol/vol) acetic acid. Gut, liver, and blood radioactivity were monitored by external gamma-counting and radioactivity in bile was measured by biliary catheter drainage into a well counter. Bile was processed by high-performance liquid chromatography to determine the amount of intact, bioactive peptide excreted over 3 h. After colonic instillation of 1 nmol of peptide, the mean (+/- SEM) biliary excretion of intact peptide was 6.4 +/- 2.0 pmol in normal rats and 49.0 +/- 20 pmol in rats with colitis (p less than 0.01). An enterohepatic circulation of synthetic N-formyl L-methionine L-leucine L-tyrosine has been demonstrated in the rat. Experimental colitis was associated with an eightfold increase in biliary excretion of this proinflammatory bacterial peptide. Proinflammatory bacterial peptides synthesized by colonic bacteria could be important in the pathophysiology of colon inflammation and its frequently associated hepatobiliary complications

  13. Chemotactic signal transduction and phosphate metabolism as adaptive strategies during citrus canker induction by Xanthomonas citri.

    Science.gov (United States)

    Moreira, Leandro Marcio; Facincani, Agda Paula; Ferreira, Cristiano Barbalho; Ferreira, Rafael Marine; Ferro, Maria Inês Tiraboshi; Gozzo, Fabio Cesar; de Oliveira, Julio Cezar Franco; Ferro, Jesus Aparecido; Soares, Márcia Regina

    2015-03-01

    The genome of Xanthomonas citri subsp. Citri strain 306 pathotype A (Xac) was completely sequenced more than 10 years; to date, few studies involving functional genomics Xac and its host compatible have been developed, specially related to adaptive events that allow the survival of Xac within the plant. Proteomic analysis of Xac showed that the processes of chemotactic signal transduction and phosphate metabolism are key adaptive strategies during the interaction of a pathogenic bacterium with its plant host. The results also indicate the importance of a group of proteins that may not be directly related to the classical virulence factors, but that are likely fundamental to the success of the initial stages of the infection, such as methyl-accepting chemotaxis protein (Mcp) and phosphate specific transport (Pst). Furthermore, the analysis of the mutant of the gene pstB which codifies to an ABC phosphate transporter subunit revealed a complete absence of citrus canker symptoms when inoculated in compatible hosts. We also conducted an in silico analysis which established the possible network of genes regulated by two-component systems PhoPQ and PhoBR (related to phosphate metabolism), and possible transcriptional factor binding site (TFBS) motifs of regulatory proteins PhoB and PhoP, detaching high degree of conservation of PhoB TFBS in 84 genes of Xac genome. This is the first time that chemotaxis signal transduction and phosphate metabolism were therefore indicated to be fundamental to the process of colonization of plant tissue during the induction of disease associated with Xanthomonas genus bacteria. PMID:25403594

  14. Coccidioides Endospores and Spherules Draw Strong Chemotactic, Adhesive, and Phagocytic Responses by Individual Human Neutrophils.

    Directory of Open Access Journals (Sweden)

    Cheng-Yuk Lee

    Full Text Available Coccidioides spp. are dimorphic pathogenic fungi whose parasitic forms cause coccidioidomycosis (Valley fever in mammalian hosts. We use an innovative interdisciplinary approach to analyze one-on-one encounters between human neutrophils and two forms of Coccidioides posadasii. To examine the mechanisms by which the innate immune system coordinates different stages of the host response to fungal pathogens, we dissect the immune-cell response into chemotaxis, adhesion, and phagocytosis. Our single-cell technique reveals a surprisingly strong response by initially quiescent neutrophils to close encounters with C. posadasii, both from a distance (by complement-mediated chemotaxis as well as upon contact (by serum-dependent adhesion and phagocytosis. This response closely resembles neutrophil interactions with Candida albicans and zymosan particles, and is significantly stronger than the neutrophil responses to Cryptococcus neoformans, Aspergillus fumigatus, and Rhizopus oryzae under identical conditions. The vigorous in vitro neutrophil response suggests that C. posadasii evades in vivo recognition by neutrophils through suppression of long-range mobilization and recruitment of the immune cells. This observation elucidates an important paradigm of the recognition of microbes, i.e., that intact immunotaxis comprises an intricate spatiotemporal hierarchy of distinct chemotactic processes. Moreover, in contrast to earlier reports, human neutrophils exhibit vigorous chemotaxis toward, and frustrated phagocytosis of, the large spherules of C. posadasii under physiological-like conditions. Finally, neutrophils from healthy donors and patients with chronic coccidioidomycosis display subtle differences in their responses to antibody-coated beads, even though the patient cells appear to interact normally with C. posadasii endospores.

  15. Chemotactic signal transduction and phosphate metabolism as adaptive strategies during citrus canker induction by Xanthomonas citri.

    Science.gov (United States)

    Moreira, Leandro Marcio; Facincani, Agda Paula; Ferreira, Cristiano Barbalho; Ferreira, Rafael Marine; Ferro, Maria Inês Tiraboshi; Gozzo, Fabio Cesar; de Oliveira, Julio Cezar Franco; Ferro, Jesus Aparecido; Soares, Márcia Regina

    2015-03-01

    The genome of Xanthomonas citri subsp. Citri strain 306 pathotype A (Xac) was completely sequenced more than 10 years; to date, few studies involving functional genomics Xac and its host compatible have been developed, specially related to adaptive events that allow the survival of Xac within the plant. Proteomic analysis of Xac showed that the processes of chemotactic signal transduction and phosphate metabolism are key adaptive strategies during the interaction of a pathogenic bacterium with its plant host. The results also indicate the importance of a group of proteins that may not be directly related to the classical virulence factors, but that are likely fundamental to the success of the initial stages of the infection, such as methyl-accepting chemotaxis protein (Mcp) and phosphate specific transport (Pst). Furthermore, the analysis of the mutant of the gene pstB which codifies to an ABC phosphate transporter subunit revealed a complete absence of citrus canker symptoms when inoculated in compatible hosts. We also conducted an in silico analysis which established the possible network of genes regulated by two-component systems PhoPQ and PhoBR (related to phosphate metabolism), and possible transcriptional factor binding site (TFBS) motifs of regulatory proteins PhoB and PhoP, detaching high degree of conservation of PhoB TFBS in 84 genes of Xac genome. This is the first time that chemotaxis signal transduction and phosphate metabolism were therefore indicated to be fundamental to the process of colonization of plant tissue during the induction of disease associated with Xanthomonas genus bacteria.

  16. Chemotactic and mitogenic stimuli of neuronal apoptosis in patients with medically intractable temporal lobe epilepsy

    Science.gov (United States)

    Fiala, Milan; Avagyan, Hripsime; Merino, Jose Joaquin; Bernas, Michael; Valdivia, Juan; Espinosa-Jeffrey, Araceli; Witte, Marlys; Weinand, Martin

    2012-01-01

    To identify the upstream signals of neuronal apoptosis in patients with medically intractable temporal lobe epilepsy (TLE), we evaluated by immunohistochemistry and confocal microscopy brain tissues of 13 TLE patients and 5 control patients regarding expression of chemokines and cell-cycle proteins. The chemokine RANTES (CCR5) and other CC-chemokines and apoptotic markers (caspase-3, -8, -9) were expressed in lateral temporal cortical and hippocampal neurons of TLE patients, but not in neurons of control cases. The chemokine RANTES is usually found in cytoplasmic and extracellular locations. However, in TLE neurons, RANTES was displayed in an unusual location, the neuronal nuclei. In addition, the cell-cycle regulatory transcription factor E2F1 was found in an abnormal location in neuronal cytoplasm. The pro-inflammatory enzyme cyclooxygenase-2 and cytokine interleukin-1β were expressed both in neurons of patients suffering from temporal lobe epilepsy and from cerebral trauma. The vessels showed fibrin leakage, perivascular macrophages and expression of IL-6 on endothelial cells. In conclusion, the cytoplasmic effects of E2F1 and nuclear effects of RANTES might have novel roles in neuronal apoptosis of TLE neurons and indicate a need to develop new medical and/or surgical neuroprotective strategies against apoptotic signaling by these molecules. Both RANTES and E2F1 signaling are upstream from caspase activation, thus the antagonists of RANTES and/or E2F1 blockade might be neuroprotective for patients with medically intractable temporal lobe epilepsy. The results have implications for the development of new medical and surgical therapies based on inhibition of chemotactic and mitogenic stimuli of neuronal apoptosis in patients with medically intractable temporal lobe epilepsy. PMID:22444245

  17. Sonic hedgehog is a chemotactic neural crest cell guide that is perturbed by ethanol exposure.

    Science.gov (United States)

    Tolosa, Ezequiel J; Fernández-Zapico, Martín E; Battiato, Natalia L; Rovasio, Roberto A

    2016-01-01

    Our aim was to understand the involvement of Sonic hedgehog (Shh) morphogen in the oriented distribution of neural crest cells (NCCs) toward the optic vesicle and to look for potential disorders of this guiding mechanism after ethanol exposure. In vitro directional analysis showed the chemotactic response of NCCs up Shh gradients and to notochord co-cultures (Shh source) or to their conditioned medium, a response inhibited by anti-Shh antibody, receptor inhibitor cyclopamine and anti-Smo morpholino (MO). Expression of the Ptch-Smo receptor complex on in vitro NCCs was also shown. In whole embryos, the expression of Shh mRNA and protein was seen in the ocular region, and of Ptch, Smo and Gli/Sufu system on cephalic NCCs. Anti-Smo MO or Ptch-mutated plasmid (Ptch1(Δloop2)) impaired cephalic NCC migration/distribution, with fewer cells invading the optic region and with higher cell density at the homolateral mesencephalic level. Beads embedded with cyclopamine (Smo-blocking) or Shh (ectopic signal) supported the role of Shh as an in vivo guide molecule for cephalic NCCs. Ethanol exposure perturbed in vitro and in vivo NCC migration. Early stage embryos treated with ethanol, in a model reproducing Fetal Alcohol Syndrome, showed later disruptions of craniofacial development associated with abnormal in situ expression of Shh morphogen. The results show the Shh/Ptch/Smo-dependent migration of NCCs toward the optic vesicle, with the support of specific inactivation with genetic and pharmacological tools. They also help to understand mechanisms of accurate distribution of embryonic cells and of their perturbation by a commonly consumed teratogen, and demonstrate, in addition to its other known developmental functions, a new biological activity of cellular guidance for Shh. PMID:26979762

  18. Modulation of signalling in neutrophils activated by a chemotactic peptide: calcium regulates diacyl glycerol metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Korchak, H.M.; Vosshall, L.B.; Lundquist, K.F.

    1987-05-01

    Neutrophils activated by ligands such as the chemotactic peptide f-Met-Leu-Phe (FMLP) generate superoxide anion (O/sub 2//sup -/) and release specific and azurophil granule contents. The signalling for this response is thought to involve both elevated cytosolic Ca and protein kinase C activity. Receptor-occupation triggers a phospholipase C to cleave phosphatidyl inositol 4,5 bisphosphate (PIP/sub 2/) yielding inositol 1,4,5 trisphosphate, (IP/sub 3/), a trigger for intracellular Ca release, and diacyl glycerol (DG), which together with Ca activates protein kinase C. The DG can be metabolized to phosphatidic acid (PA). FMLP triggered a rapid increase in cytosolic Ca (fura-2). Loading cells with MAPTAM, and intracellular Ca buffer, suppressed this Ca transient in FMLP activated cells and inhibited O/sub 2//sup -/ generation to 12.5% of control, beta-glucuronidase release to 40.3% of control and lysozyme release to 55.1% of control. FMLP triggered a prompt decrease in PIP/sub 2/ in cells pre-labelled with /sup 32/P or /sup 3/H-inositol and an increase in PA and release of /sup 3/H-IP/sub 3/. A rapid increase in /sup 14/C-DG levels was also observed in /sup 14/C-glycerol pre-loaded cells activated by FMLP. Suppression of the Ca transient by buffering with MAPTAM inhibited elevation of /sup 14/C-DG. Breakdown of PIP/sub 2/ was not inhibited and elevation of /sup 32/P-PA was enhanced in MAPTAM loaded cells. Conversely, 200nM ionomycin which elevated cytosolic Ca to an equivalent level to 10/sup -7/M FMLP, triggered a rise in /sup 14/C-DG but not in PA.

  19. MiR-124 suppresses the chemotactic migration of rat mesenchymal stem cells toward HGF by downregulating Wnt/β-catenin signaling.

    Science.gov (United States)

    Yue, Qing; Zhang, Yu; Li, Xianyang; He, Lihong; Hu, Ya'nan; Wang, Xianyao; Xu, Xiaojing; Shen, Yixin; Zhang, Huanxiang

    2016-09-01

    Mesenchymal stem cells (MSCs) exhibit the potential to repair a wide variety of injured adult tissues. The migration capability of MSCs is an important determinant of the efficiency of MSC transplant therapy. MicroRNAs (miRNAs) are increasingly implicated in regulating the migration of MSCs. Herein, we show that the expression of miR-124 was downregulated in rat MSCs (rMSCs) treated with hepatocyte growth factor (HGF). Overexpression of miR-124 significantly reduced the chemotactic migration of rMSCs toward HGF, while inhibition of endogenous miR-124 promoted the chemotactic migration. A further study revealed that miR-124 directly targeted FZD4 and LRP6, which encode a receptor and co-receptor of the Wnt/β-catenin signaling pathway, respectively, thus reducing the activity of this signaling. Consistently, activation of the Wnt/β-catenin signaling pathway by LiCl and ΔN89β-catenin rescued the inhibitory effect of miR-124 on the chemotactic migration of rMSCs toward HGF, while inhibition of Wnt/β-catenin signaling by FH535 abrogated the enhanced chemotactic response achieved by the miR-124 inhibitor. Collectively, our study demonstrates that miR-124 downregulates Wnt/β-catenin signaling via targeting FZD4 and LRP6 and thus suppresses the chemotactic migration of rMSCs toward HGF.

  20. Monocyte chemoattractant protein-1, trans-forming growth factor-β1, nerve growth factor, resistin and hyaluronic acid as serum markers:comparison between recurrent acute and chronic pancreatitis

    Institute of Scientific and Technical Information of China (English)

    M Ganesh Kamath; C Ganesh Pai; Asha Kamath; Annamma Kurien

    2016-01-01

    BACKGROUND: Diagnostic parameters that can predict the presence of chronic pancreatitis (CP) in patients with recur-rent pain due to pancreatitis would help to direct appropri-ate therapy. This study aimed to compare the serum levels of monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-β1 (TGF-β1), nerve growth factor (NGF), resis-tin and hyaluronic acid (HA) in patients with recurrent acute pancreatitis (RAP) and CP to assess their ability to differenti-ate the two conditions. METHODS: Levels of serum markers assessed by enzyme-linked immunosorbent assay (ELISA) were prospectively com-pared in consecutive patients with RAP, CP and in controls, and stepwise discriminant analysis was performed to identify the markers differentiating RAP from CP. RESULTS: One hundred and thirteen consecutive patients (RAP=32, CP=81) and 78 healthy controls were prospectively enrolled. The mean (SD) age of the patients was 32.0 (14.0) years; 89 (78.8%) were male. All markers were signiifcantly higher in CP patients than in the controls (P CONCLUSION: Serum resistin is a promising marker to dif-ferentiate between RAP and CP and needs validation in future studies, especially in those with early CP.

  1. Quantitative modeling of Escherichia coli chemotactic motion in environments varying in space and time.

    Directory of Open Access Journals (Sweden)

    Lili Jiang

    2010-04-01

    Full Text Available Escherichia coli chemotactic motion in spatiotemporally varying environments is studied by using a computational model based on a coarse-grained description of the intracellular signaling pathway dynamics. We find that the cell's chemotaxis drift velocity v(d is a constant in an exponential attractant concentration gradient [L] proportional, variantexp(Gx. v(d depends linearly on the exponential gradient G before it saturates when G is larger than a critical value G(C. We find that G(C is determined by the intracellular adaptation rate k(R with a simple scaling law: G(C infinity k(1/2(R. The linear dependence of v(d on G = d(ln[L]/dx directly demonstrates E. coli's ability in sensing the derivative of the logarithmic attractant concentration. The existence of the limiting gradient G(C and its scaling with k(R are explained by the underlying intracellular adaptation dynamics and the flagellar motor response characteristics. For individual cells, we find that the overall average run length in an exponential gradient is longer than that in a homogeneous environment, which is caused by the constant kinase activity shift (decrease. The forward runs (up the gradient are longer than the backward runs, as expected; and depending on the exact gradient, the (shorter backward runs can be comparable to runs in a spatially homogeneous environment, consistent with previous experiments. In (spatial ligand gradients that also vary in time, the chemotaxis motion is damped as the frequency omega of the time-varying spatial gradient becomes faster than a critical value omega(c, which is controlled by the cell's chemotaxis adaptation rate k(R. Finally, our model, with no adjustable parameters, agrees quantitatively with the classical capillary assay experiments where the attractant concentration changes both in space and time. Our model can thus be used to study E. coli chemotaxis behavior in arbitrary spatiotemporally varying environments. Further experiments are

  2. Chemotactic response of plant-growth-promoting bacteria towards roots of vesicular-arbuscular mycorrhizal tomato plants.

    Science.gov (United States)

    Gupta Sood, Sushma

    2003-08-01

    The chemotactic responses of the plant-growth-promoting rhizobacteria Azotobacter chroococcum and Pseudomonas fluorescens to roots of vesicular-arbuscular mycorrhizal (Glomus fasciculatum) tomato plants were determined. A significantly (P=0.05) greater number of bacterial cells of wild strains were attracted towards vesicular-arbuscular mycorrhizal tomato roots compared to non-vesicular-arbuscular mycorrhizal tomato roots. Substances exuded by roots served as chemoattractants for these bacteria. P. fluorescens was strongly attracted towards citric and malic acids, which were predominant constituents in root exudates of tomato plants. A. chroococcum showed a stronger response towards sugars than amino acids, but the response was weakest towards organic acids. The effects of temperature, pH, and soil water matric potential on bacterial chemotaxis towards roots were also investigated. In general, significantly (P=0.05) greater chemotactic responses of bacteria were observed at higher water matric potentials (0, -1, and -5 kPa), slightly acidic to neutral pH (6, 6.5 and 7), and at 20-30 degrees C (depending on the bacterium) than in other environmental conditions. It is suggested that chemotaxis of P. fluorescens and A. chroococcum towards roots and their exudates is one of the several steps in the interaction process between bacteria and vesicular-arbuscular mycorrhizal roots. PMID:19719591

  3. In vitro inhibitory effects of Moringa oleifera leaf extract and its major components on chemiluminescence and chemotactic activity of phagocytes.

    Science.gov (United States)

    Vongsak, Boonyadist; Gritsanapan, Wandee; Wongkrajang, Yuvadee; Jantan, Ibrahim

    2013-11-01

    The ethanol extract of Moringa oleifera Lam. leaves and its major constituents, crypto-chlorogenic acid, quercetin 3-O-glucoside and kaempferol 3-O-glucoside, were investigated on the respiratory burst of human whole blood and isolated human polymorphonuclear leukocytes (PMNs) using a luminol-based chemiluminescence assay. The chemotactic migration of PMNs was also investigated using the Boyden chamber technique. The ethanol extract demonstrated inhibitory activities on the oxidative burst and the chemotactic migration of PMNs. Quercetin 3-O-glucoside, crypto-chlorogenic acid, and kaempferol 3-O-glucoside, isolated from the extract, expressed relatively strong inhibitory activity on the oxidative burst of PMNs with IC50 values of 4.1, 6.7 and 7.0 microM, respectively, comparable with that of aspirin. They also demonstrated strong inhibition of chemotatic migration of PMNs with IC50 values of 9.5, 15.9 and 18.2 microM, respectively. The results suggest that M. oleifera leaves could modulate the immune response of human phagocytes, linking to its ethnopharmacological use as an anti-inflammatory agent. The immunomodulating activity of the plant was mainly due to its major components.

  4. Chronic Alcohol-Induced microRNA-155 Contributes to Neuroinflammation in a TLR4-Dependent Manner in Mice

    OpenAIRE

    Lippai, Dora; Bala, Shashi; Csak, Timea; Evelyn A. Kurt-Jones; Szabo, Gyongyi

    2013-01-01

    Introduction Alcohol-induced neuroinflammation is mediated by pro-inflammatory cytokines and chemokines including tumor necrosis factor-α (TNFα), monocyte chemotactic protein-1 (MCP1) and interleukin-1-beta (IL-1β). Toll-like receptor-4 (TLR4) pathway induced nuclear factor-κB (NF-κB) activation is involved in the pathogenesis of alcohol-induced neuroinflammation. Inflammation is a highly regulated process. Recent studies suggest that microRNAs (miRNAs) play crucial role in fine tuning gene e...

  5. 单核细胞趋化蛋白1和骨形成蛋白7在病理性瘢痕中的表达%Expression of monocyte ehemoattraetant protein-1 and bone morphogenic protein-7 in pathologic scars

    Institute of Scientific and Technical Information of China (English)

    李永涛; 王喜梅; 刘林嶓; 张建文; 袁德品

    2011-01-01

    背景:单核细胞趋化蛋白1 是新近明确的对单核/巨噬细胞有趋化和激活双重作用的趋化因子,骨形成蛋白7 作为一种新发现的纤维化负性调节因子逐渐成为抗组织纤维化治疗的研究热点,但两者对病理性瘢痕形成中组织纤维化作用的研究至今鲜有报道.目的:研究单核细胞趋化蛋白1,骨形成蛋白7 在病理性瘢痕中的表达水平.方法:采用免疫组织化学方法检测单核细胞趋化蛋白1、骨形成蛋白7 在25 例瘢痕疙瘩、30 例增生性瘢痕、24 例非病理瘢痕和20 例正常皮肤组织中的表达水平.所有标本均来自2008-07/2010-01 郑州大学第一附属医院整形外科住院患者,且均无皮肤疾病、结缔组织病、传染病、恶性肿瘤和其他重要脏器疾病,术前无射线治疗、激光治疗及免疫治疗史,其中所取瘢痕组织来自于临床诊断明确的瘢痕患者.结果与结论:单核细胞趋化蛋白1 在瘢痕疙瘩、增生性瘢痕中的阳性表达率均高于非病理性瘢痕与正常皮肤组织(P < 0.05),骨形成蛋白7 阳性表达率均降低(P < 0.05),两者阳性表达率在病理性瘢痕(瘢痕疙瘩和增生性瘢痕)中呈明显负相关(r = -0.639,P < 0.01).结果显示,在病理性瘢痕的形成过程中单核细胞趋化蛋白1 表达上调,而骨形成蛋白7 表达下调.%BACKGROUND: Monocyte ehemoattraetant protein-1 (MCP-1) has been shown chemotaxis and activation effect on mononuclear/macrophage. As a newly found negative-regulatory factor, bone morphogenic protein-7 (BMP-7) has aroused increasing attention in the treatment of tissue fibrosis. However, the effects of MCP-1 and BMP-7 on tissue fibrosis during pathologic scars remain poorly understood.OBJECTIVE: To investigate the expression of MCP-1 and BMP-7 in pathologic scars.METHODS: SP immunohistochemical method was used to detect the expressions of MCP-1 and BMP-7 in 25 cases of keloid, 30 cases of hypertrophic scars, 24 cases of

  6. Nf1+/- monocytes/macrophages induce neointima formation via CCR2 activation.

    Science.gov (United States)

    Bessler, Waylan K; Kim, Grace; Hudson, Farlyn Z; Mund, Julie A; Mali, Raghuveer; Menon, Keshav; Kapur, Reuben; Clapp, D Wade; Ingram, David A; Stansfield, Brian K

    2016-03-15

    Persons with neurofibromatosis type 1 (NF1) have a predisposition for premature and severe arterial stenosis. Mutations in the NF1 gene result in decreased expression of neurofibromin, a negative regulator of p21(Ras), and increases Ras signaling. Heterozygous Nf1 (Nf1(+/-)) mice develop a marked arterial stenosis characterized by proliferating smooth muscle cells (SMCs) and a predominance of infiltrating macrophages, which closely resembles arterial lesions from NF1 patients. Interestingly, lineage-restricted inactivation of a single Nf1 allele in monocytes/macrophages is sufficient to recapitulate the phenotype observed in Nf1(+/-) mice and to mobilize proinflammatory CCR2+ monocytes into the peripheral blood. Therefore, we hypothesized that CCR2 receptor activation by its primary ligand monocyte chemotactic protein-1 (MCP-1) is critical for monocyte infiltration into the arterial wall and neointima formation in Nf1(+/-) mice. MCP-1 induces a dose-responsive increase in Nf1(+/-) macrophage migration and proliferation that corresponds with activation of multiple Ras kinases. In addition, Nf1(+/-) SMCs, which express CCR2, demonstrate an enhanced proliferative response to MCP-1 when compared with WT SMCs. To interrogate the role of CCR2 activation on Nf1(+/-) neointima formation, we induced neointima formation by carotid artery ligation in Nf1(+/-) and WT mice with genetic deletion of either MCP1 or CCR2. Loss of MCP-1 or CCR2 expression effectively inhibited Nf1(+/-) neointima formation and reduced macrophage content in the arterial wall. Finally, administration of a CCR2 antagonist significantly reduced Nf1(+/-) neointima formation. These studies identify MCP-1 as a potent chemokine for Nf1(+/-) monocytes/macrophages and CCR2 as a viable therapeutic target for NF1 arterial stenosis. PMID:26740548

  7. Beta-adrenergic receptor agonists induce the release of granulocyte chemotactic protein-2, oncostatin M, and vascular endothelial growth factor from macrophages

    NARCIS (Netherlands)

    Verhoeckx, K.C.M.; Doornbos, R.P.; Witkamp, R.F.; Greef, de J.; Rodenburg, R.J.T.

    2006-01-01

    Vascular endothelial growth factor (VEGF), oncostatin M (OSM), and granulocyte chemotactic protein-2 (GCP-2/CXCL6) are up-regulated in U937 macrophages and peripheral blood macrophages exposed to LPS, beta-adrenergic receptor (ß2-AR) agonists (e.g. zilpaterol, and clenbuterol) and some other agents

  8. Beta-adrenergic receptor agonists induce the release of granulocyte chemotactic protein-2, oncostatin M, and vascular endothelial growth factor from macrophages

    NARCIS (Netherlands)

    Verhoeckx, K.C.; Doornbos, R.P.; Witkamp, R.F.; Greef, J. van der; Rodenburg, R.J.T.

    2006-01-01

    Vascular endothelial growth factor (VEGF), oncostatin M (OSM), and granulocyte chemotactic protein-2 (GCP-2/CXCL6) are up-regulated in U937 macrophages and peripheral blood macrophages exposed to LPS, beta-adrenergic receptor (beta2-AR) agonists (e.g. zilpaterol, and clenbuterol) and some other agen

  9. Beta-adrenergic receptor agonists induce the release of granulocyte chemotactic protein-2, oncostatin M, and vascular endothelial growth factor from macrophages

    NARCIS (Netherlands)

    Verhoeckx, K.C.M.; Doornbos, R.P.; Witkamp, R.F.; Greef, J. van der; Rodenburg, R.J.T.

    2006-01-01

    Vascular endothelial growth factor (VEGF), oncostatin M (OSM), and granulocyte chemotactic protein-2 (GCP-2/CXCL6) are up-regulated in U937 macrophages and peripheral blood macrophages exposed to LPS, beta-adrenergic receptor (β2-AR) agonists (e.g. zilpaterol, and clenbuterol) and some other agents

  10. Migration of Chemotactic Bacteria Transverse to Flow in Response to a Benzoate Source Plume Created in a Saturated Sand-Packed Microcosm

    Science.gov (United States)

    Ford, R.; Boser, B.

    2012-12-01

    Bioremediation processes depend on contact between microbial populations and the groundwater contaminants that they biodegrade. Chemotaxis, the ability of bacteria to sense a chemical gradient and swim preferentially toward locations of higher concentration, can enhance the transport of bacteria toward contaminant sources that may not be readily accessible by advection and dispersion alone. A two-dimensional rectangular-shaped microcosm packed with quartz sand was used to quantify the effect of chemotaxis on the migration of bacteria within a saturated model aquifer system. Artificial groundwater was pumped through the microcosm at a rate of approximately 1 m/day. A plume of sodium benzoate was created by continuous injection into an upper port of the microcosm to generate a chemical gradient in the vertical direction transverse to flow. Chemotactic bacteria, Pseudomonas putida F1, or the nonchemotactic mutant, P. putida F1 CheA, were injected with a conservative tracer in a port several centimeters below the benzoate position. As the injectates traversed the one-meter length of the microcosm, samples were collected from a dozen effluent ports to determine vertical concentration distributions for the bacteria, benzoate and tracer. A moment analysis was implemented to estimate the center of mass, variance, and skewness of the concentration profiles. The transverse dispersion coefficient and the transverse dispersivity for chemotactic and nonchemotactic bacteria were also evaluated. Experiments performed with a continuous injection of bacteria showed that the center of mass for chemotactic bacteria was closer to the benzoate source on average than the nonchemotactic control (relative to the conservative tracer). These results demonstrated that chemotaxis can increase bacterial transport toward contaminants, potentially enhancing the effectiveness of in situ bioremediation. Experiments with 2 cm and 3 cm spacing between bacteria and benzoate injection locations were

  11. Chemotactic Activity of Cyclophilin A in the Skin Mucus of Yellow Catfish (Pelteobagrus fulvidraco and Its Active Site for Chemotaxis

    Directory of Open Access Journals (Sweden)

    Farman Ullah Dawar

    2016-08-01

    Full Text Available Fish skin mucus is a dynamic barrier for invading pathogens with a variety of anti-microbial enzymes, including cyclophilin A (CypA, a multi-functional protein with peptidyl-prolyl cis/trans isomerase (PPIase activity. Beside various other immunological functions, CypA induces leucocytes migration in vitro in teleost. In the current study, we have discovered several novel immune-relevant proteins in yellow catfish skin mucus by mass spectrometry (MS. The CypA present among them was further detected by Western blot. Moreover, the CypA present in the skin mucus displayed strong chemotactic activity for yellow catfish leucocytes. Interestingly, asparagine (like arginine in mammals at position 69 was the critical site in yellow catfish CypA involved in leucocyte attraction. These novel efforts do not only highlight the enzymatic texture of skin mucus, but signify CypA to be targeted for anti-inflammatory therapeutics.

  12. Crosstalk between medulloblastoma cells and endothelium triggers a strong chemotactic signal recruiting T lymphocytes to the tumor microenvironment.

    Directory of Open Access Journals (Sweden)

    Vita S Salsman

    Full Text Available Cancer cells can live and grow if they succeed in creating a favorable niche that often includes elements from the immune system. While T lymphocytes play an important role in the host response to tumor growth, the mechanism of their trafficking to the tumor remains poorly understood. We show here that T lymphocytes consistently infiltrate the primary brain cancer, medulloblastoma. We demonstrate, both in vitro and in vivo, that these T lymphocytes are attracted to tumor deposits only after the tumor cells have interacted with tumor vascular endothelium. Macrophage Migration Inhibitory Factor (MIF" is the key chemokine molecule secreted by tumor cells which induces the tumor vascular endothelial cells to secrete the potent T lymphocyte attractant "Regulated upon Activation, Normal T-cell Expressed, and Secreted (RANTES." This in turn creates a chemotactic gradient for RANTES-receptor bearing T lymphocytes. Manipulation of this pathway could have important therapeutic implications.

  13. Multiscale dynamics of biological cells with chemotactic interactions: from a discrete stochastic model to a continuous description

    CERN Document Server

    Alber, M; Glimm, T; Lushnikov, P M; Alber, Mark; Chen, Nan; Glimm, Tilmann; Lushnikov, Pavel M.

    2006-01-01

    The Cellular Potts Model (CPM) has been used for simulating various biological phenomena such as differential adhesion, fruiting body formation of the slime mold Dictyostelium discoideum, angiogenesis, cancer invasion, chondrogenesis in embryonic vertebrate limbs, and many others. In this paper, we derive continuous limit of discrete one dimensional CPM with the chemotactic interactions between cells in the form of a Fokker-Planck equation for the evolution of the cell probability density function. This equation is then reduced to the classical macroscopic Keller-Segel model. In particular, all coefficients of the Keller-Segel model are obtained from parameters of the CPM. Theoretical results are verified numerically by comparing Monte Carlo simulations for the CPM with numerics for the Keller-Segel model.

  14. Plasma Levels of Monocyte Chemotactic Protein 3 and Beta-Nerve Growth Factor Increase with Amnestic Mild Cognitive Impairment

    Institute of Scientific and Technical Information of China (English)

    Kang Soo Lee; Ji Hyung Chung; Kyung Hye Lee; Min-Jeong Shin; Byoung Hoon Oh; Soo Hyung Lee; Chang Hyung Hong

    2009-01-01

    A number of studies have investigated peripheral inflammatory indices, including plasma cytokines and related molecules according to subtypes of dementia, but not in mild cognitive impairment (MCI). In this study, we used multiplex cytokine assay to assess the plasma levels of 22 cytokines in patients with MCI subtyped as amnestic and non-amnestic, according to cognitive features. When comparing the levels of plasma growth factors, chemokines and cytokines, plasma levels of monocyte chemotactic protein 3 (MCP-3), and beta-nerve growth factor (β-NGF) in these two groups, they were found to be significantly higher in amnestic MCI patients than in non-amnestic MCI patients, after adjusting for age and gender. This suggests that plasma MCP-3 and β-NGF may be useful in differentiating subtypes of MCI. Cellular & Molecular Immunology.

  15. TNF-alpha associated with extracellular matrix fibronectin provides a stop signal for chemotactically migrating T cells.

    Science.gov (United States)

    Franitza, S; Hershkoviz, R; Kam, N; Lichtenstein, N; Vaday, G G; Alon, R; Lider, O

    2000-09-01

    The migration of T cells into extravascular sites of inflammation is regulated by information derived from the molecular structure of the invaded tissue and from chemokine and cytokine gradients in the context of the extracellular matrix (ECM). Although recent studies have highlighted the role of particular chemoattractants in leukocyte migration, to date little is known about how specific combinations of contextual signals control the migration of leukocytes and their localization at sites of inflammation. Here we studied the interplay between a pleiotropic cytokine, TNF-alpha, and two prototypic chemoattractants, RANTES and stromal cell-derived factor-1alpha (SDF-1alpha), on human CD45RO+ T cells migrating within an ECM-like context. For this purpose, we used a newly constructed three-dimensional gel system designed to follow, in real time, the migration of individual leukocytes along chemotactic gradients in vitro. We found that TNF-alpha, which binds the ECM protein fibronectin and lacks adhesion- and migration-promoting effects of its own, can act as a proadhesive cytokine on T cells exposed to RANTES and SDF-1alpha. Furthermore, fibronectin-complexed TNF-alpha provided anchorage signals to the T cells as they moved directionally along chemoattractive gradients. This effect of TNF-alpha required an intact TNF-alpha receptor II subtype on the migrating T cells. The anchoring effect of TNF-alpha appears to be specific; IL-2, an integrin-activating proadhesive cytokine, does not transmit stoppage signals to T cell migration induced by RANTES. Thus, TNF-alpha present in the ECM at sites of inflammation may function to anchor T cells recruited to these sites by chemotactic signals. PMID:10946305

  16. The release of eosinophil chemotactic activity and eosinophil chemokinesis inhibitory activity by mononuclear cells from atopic asthmatic and non-atopic subjects

    Directory of Open Access Journals (Sweden)

    J. Grzegorczyk

    2000-01-01

    Full Text Available The goal of our study was to assess the chemotactic activity for eosinophils (ECA and neutrophils (NCA and histamine releasing activity (HRA in crude supernatants of mononuclear cells in monosensitized atopic asthmatics and healthy controls. Chemotactic activity for ECA and neutrophils was measured in supernatants of cultured mononuclear cells with modified Boyden’s chamber and HRA was assessed on healthy donor basophils. With respect to ECA generation two distinct subgroups of subjects were distinguished: releasers [ECA (+] and non-releasers [ECA (–]. In atopic and non-atopic ECA (+ the mean ECA index was 3.78 ± 0.49 and 2.47 ± 0.27 respectively (P > 0.05. Supernatants from the remaining subjects (seven of 22 atopic and five of 11 non-atopic did not express ECA, but revealed significant inhibitory activity for chemokinesis of eosinophils (mean chemotactic index 0.25 ± 0.16 and 0.48 ± 0.22 for atopic and non-atopic non-releasers respectively. Stimulation with antigen of MNC from atopic and with PHA from non-atopic ECA (– restored cells ability to release ECA. Sephadex gel chromatography revealed that supernatants of MNC contained chemotactic and chemokinesis inhibitory activity in different fractions. The spontaneous productions of NCA and HRA by mononuclear cells was sim ilar in ECA releasers and non-releasers, although the HRA was higher following stimulation with PHA in the non-atopic ECA (+ subgroup. Our study demonstrated, for the first time, that MNC are capable of generating not only chemotactic activity but also chemokinesis inhibitory activity for eosinophils.

  17. Effect of atorvastatin on advanced glycation end products induced monocyte chemoattractant protein-1 expression in cultured human endothelial cells%阿托伐他汀对晚期糖基化终末产物诱导的人内皮细胞单核细胞趋化蛋白-1mRNA表达影响及其机制的实验研究

    Institute of Scientific and Technical Information of China (English)

    徐尚华; 王科峰; 许昌声; 谢良地

    2011-01-01

    Objective To investigate the effects of atorvastatin on advanced glycation end products (AGE) induced monocyte chemoattractant protein-1(MCP-1) expression in human umbilical vein endothelial cells(HUVECs)and whether this effect could be linked to peroxisome proliferator-activated receptor-γ (PPAR-γ) and nuclear factor-κB(NF-κB).Methods Grouping: (1)Blank control group;(2)BSA group;(3)AGE group:cells were incubated with different concentrations of AGE(10-4,10-3, 10-2 and 10-1g/L)for 24 hours; (4)AGE+Atorvastatin group: cells were incubated with different concentrations of atorvastatin(0.1,1,10 μmol/L)for 1 hour,then incubated with AGE (10-1 g/L) for 24 hours; (5)PPAR-γ agonist(15 d-PGJ2)group: cells were incubated with 15 d-PGJ2(10 μmol/L)for 1 hour,then incubated with AGE (10-1g/L) for 24 hours;(6)PPAR-γ inhibitor(GW9662)group:cells were incubated with GW9662(5000 nmol/L)for 1 hour,then incubated with atorvastatin (1 μmol/L)and AGE (10-1g/L) for 24 hours. Collagenase was used to isolate the endothelial cell from human umbilical vein;RT-PCR was performed to examine the mRNA expression of MCP-1 and PPAR-γ;Western blot was performed to detect NF-κB p65 protein.Results (1) The expression of MCP-1 mRNA was increased in proportion with increasing concentrations of AGEs which could be blocked by atorvastatin in a dose-dependent manner. (2) AGE(10-1g/L)significantly downregulated the expression of PPAR-γ mRNA(0.22±0.08 vs. 0.69±0.09, P<0.01) while upregulated the expression of phospho-NF-κB p65 protein (0.78±0.06 vs. 0.31±0.01,P<0.01) and nonphospho-NF-κB p65 protein (1.61±0.16 vs. 0.59±0.14,P<0.01) comparaed with the control group which could be significantly attenuated by atorvastatin. (3) PPAR-γ agonist decreased the expression of phospho-NF-κB p65 protein (0.21±0.01 vs. 0.78±0.06, P<0.01),nonphospho-NF-κB p65 protein (0.67±0.14 vs. 1.61±0.16,P<0.01)and MCP-1 mRNA (0.17±0.02 vs. 0.93±0.12, P<0.01)compared with AGE(10-1g/L)group. (4) PPAR

  18. Structural studies of human glioma pathogenesis-related protein 1

    International Nuclear Information System (INIS)

    Structural analysis of a truncated soluble domain of human glioma pathogenesis-related protein 1, a membrane protein implicated in the proliferation of aggressive brain cancer, is presented. Human glioma pathogenesis-related protein 1 (GLIPR1) is a membrane protein that is highly upregulated in brain cancers but is barely detectable in normal brain tissue. GLIPR1 is composed of a signal peptide that directs its secretion, a conserved cysteine-rich CAP (cysteine-rich secretory proteins, antigen 5 and pathogenesis-related 1 proteins) domain and a transmembrane domain. GLIPR1 is currently being investigated as a candidate for prostate cancer gene therapy and for glioblastoma targeted therapy. Crystal structures of a truncated soluble domain of the human GLIPR1 protein (sGLIPR1) solved by molecular replacement using a truncated polyalanine search model of the CAP domain of stecrisp, a snake-venom cysteine-rich secretory protein (CRISP), are presented. The correct molecular-replacement solution could only be obtained by removing all loops from the search model. The native structure was refined to 1.85 Å resolution and that of a Zn2+ complex was refined to 2.2 Å resolution. The latter structure revealed that the putative binding cavity coordinates Zn2+ similarly to snake-venom CRISPs, which are involved in Zn2+-dependent mechanisms of inflammatory modulation. Both sGLIPR1 structures have extensive flexible loop/turn regions and unique charge distributions that were not observed in any of the previously reported CAP protein structures. A model is also proposed for the structure of full-length membrane-bound GLIPR1

  19. Structural studies of human glioma pathogenesis-related protein 1

    Energy Technology Data Exchange (ETDEWEB)

    Asojo, Oluwatoyin A., E-mail: oasojo@unmc.edu [College of Medicine, Nebraska Medical Center, Omaha, NE 68198-6495 (United States); Koski, Raymond A.; Bonafé, Nathalie [L2 Diagnostics LLC, 300 George Street, New Haven, CT 06511 (United States); College of Medicine, Nebraska Medical Center, Omaha, NE 68198-6495 (United States)

    2011-10-01

    Structural analysis of a truncated soluble domain of human glioma pathogenesis-related protein 1, a membrane protein implicated in the proliferation of aggressive brain cancer, is presented. Human glioma pathogenesis-related protein 1 (GLIPR1) is a membrane protein that is highly upregulated in brain cancers but is barely detectable in normal brain tissue. GLIPR1 is composed of a signal peptide that directs its secretion, a conserved cysteine-rich CAP (cysteine-rich secretory proteins, antigen 5 and pathogenesis-related 1 proteins) domain and a transmembrane domain. GLIPR1 is currently being investigated as a candidate for prostate cancer gene therapy and for glioblastoma targeted therapy. Crystal structures of a truncated soluble domain of the human GLIPR1 protein (sGLIPR1) solved by molecular replacement using a truncated polyalanine search model of the CAP domain of stecrisp, a snake-venom cysteine-rich secretory protein (CRISP), are presented. The correct molecular-replacement solution could only be obtained by removing all loops from the search model. The native structure was refined to 1.85 Å resolution and that of a Zn{sup 2+} complex was refined to 2.2 Å resolution. The latter structure revealed that the putative binding cavity coordinates Zn{sup 2+} similarly to snake-venom CRISPs, which are involved in Zn{sup 2+}-dependent mechanisms of inflammatory modulation. Both sGLIPR1 structures have extensive flexible loop/turn regions and unique charge distributions that were not observed in any of the previously reported CAP protein structures. A model is also proposed for the structure of full-length membrane-bound GLIPR1.

  20. Differential and time-dependent expression of monocyte chemoattractant protein-1 mRNA by astrocytes and macrophages in rat brain : Effects of ischemia and peripheral lipopolysaccharide administration

    NARCIS (Netherlands)

    Gourmala, NG; Buttini, M; Limonta, S; Sauter, A; Boddeke, HWGM

    1997-01-01

    Increasing evidence indicates a key role of chemoattractant cytokines in the accumulation of leukocytes in the central nervous system (CNS) during the course of inflammatory processes. Monocyte chemoattractant protein (MCP-1/JE), a member of the beta-chemokine (C-C chemokine) family, functions as a

  1. Cloning, bacterial expression and biological characterization of recombinant human granulocyte chemotactic protein-2 and differential expression of granulocyte chemotactic protein-2 and epithelial cell-derived neutrophil activating peptide-78 mRNAs.

    Science.gov (United States)

    Froyen, G; Proost, P; Ronsse, I; Mitera, T; Haelens, A; Wuyts, A; Opdenakker, G; Van Damme, J; Billiau, A

    1997-02-01

    Human osteosarcoma cells secrete a novel C-X-C chemokine called granulocyte chemotactic protein-2 (GCP-2), which was previously identified by amino acid sequencing of the purified natural protein. In order to understand the role of this new protein in inflammatory reactions, we cloned GCP-2 DNA sequences to generate recombinant protein and specific DNA probes and primers. By means of PCR on cloned cDNA of osteosarcoma cells induced by interleukin-1 beta and fibroblasts induced by lipopolysaccharide plus dsRNA, the complete coding domain of GCP-2 was isolated. This sequence was cloned into the bacterial expression vector pHEN1 and, after induction, GCP-2 was secreted into the periplasm of Escherichia coli. Recombinant GCP-2 (rGCP-2) was purified and characterized by SDS/PAGE as a monomeric 6.5-kDa protein and by amino-terminal sequencing. The chemoattractive potency of GCP-2 for neutrophilic granulocytes was about 10-times less than that of interleukin-8 and the minimal effective dose was 10 ng/ml. However, at optimal dose (100 ng/ml) the maximal chemotactic response was comparable with that of interleukin-8. Both characteristics correspond with those of natural GCP-2. In addition, intracellular calcium release in neutrophils by recombinant GCP-2 was achieved with as little as 10 ng/ml. Quantitation studies using reverse transcriptase and the polymerase chain reaction revealed higher GCP-2 mRNA production in normal fibroblasts than in tumor cells. When compared with epithelial-cell-derived neutrophil-activating peptide-78 (ENA-78) mRNA, the GCP-2 mRNA levels were higher in all cell lines tested. In addition, GCP-2 and ENA-78 expression seem to be differentially regulated in that phorbol ester and lipopolysaccharide have opposing effects on their mRNA induction in diploid fibroblasts and epithelial cells, respectively. Interleukin-1 was demonstrated to be a general inducer for both chemokines, while interferon-gamma down-regulates their mRNA expression. The

  2. MAVS protein is attenuated by rotavirus nonstructural protein 1.

    Directory of Open Access Journals (Sweden)

    Satabdi Nandi

    Full Text Available Rotavirus is the single, most important agent of infantile gastroenteritis in many animal species, including humans. In developing countries, rotavirus infection attributes approximately 500,000 deaths annually. Like other viruses it establishes an intimate and complex interaction with the host cell to counteract the antiviral responses elicited by the cell. Among various pattern recognition receptors (PAMPs of the host, the cytosolic RNA helicases interact with viral RNA to activate the Mitochondrial Antiviral Signaling protein (MAVS, which regulates cellular interferon response. With an aim to identify the role of different PAMPs in rotavirus infected cell, MAVS was found to degrade in a time dependent and strain independent manner. Rotavirus non-structural protein 1 (NSP1 which is a known IFN antagonist, interacted with MAVS and degraded it in a strain independent manner, resulting in a complete loss of RNA sensing machinery in the infected cell. To best of our knowledge, this is the first report on NSP1 functionality where a signaling protein is targeted unanimously in all strains. In addition NSP1 inhibited the formation of detergent resistant MAVS aggregates, thereby averting the antiviral signaling cascade. The present study highlights the multifunctional role of rotavirus NSP1 and reinforces the fact that the virus orchestrates the cellular antiviral response to its own benefit by various back up strategies.

  3. Heterochromatin protein 1 secures survival and transmission of malaria parasites.

    Science.gov (United States)

    Brancucci, Nicolas M B; Bertschi, Nicole L; Zhu, Lei; Niederwieser, Igor; Chin, Wai Hoe; Wampfler, Rahel; Freymond, Céline; Rottmann, Matthias; Felger, Ingrid; Bozdech, Zbynek; Voss, Till S

    2014-08-13

    Clonally variant expression of surface antigens allows the malaria parasite Plasmodium falciparum to evade immune recognition during blood stage infection and secure malaria transmission. We demonstrate that heterochromatin protein 1 (HP1), an evolutionary conserved regulator of heritable gene silencing, controls expression of numerous P. falciparum virulence genes as well as differentiation into the sexual forms that transmit to mosquitoes. Conditional depletion of P. falciparum HP1 (PfHP1) prevents mitotic proliferation of blood stage parasites and disrupts mutually exclusive expression and antigenic variation of the major virulence factor PfEMP1. Additionally, PfHP1-dependent regulation of PfAP2-G, a transcription factor required for gametocyte conversion, controls the switch from asexual proliferation to sexual differentiation, providing insight into the epigenetic mechanisms underlying gametocyte commitment. These findings show that PfHP1 is centrally involved in clonally variant gene expression and sexual differentiation in P. falciparum and have major implications for developing antidisease and transmission-blocking interventions against malaria. PMID:25121746

  4. Glycosylation of Dentin Matrix Protein 1 is critical for osteogenesis.

    Science.gov (United States)

    Sun, Yao; Weng, Yuteng; Zhang, Chenyang; Liu, Yi; Kang, Chen; Liu, Zhongshuang; Jing, Bo; Zhang, Qi; Wang, Zuolin

    2015-12-04

    Proteoglycans play important roles in regulating osteogenesis. Dentin matrix protein 1 (DMP1) is a highly expressed bone extracellular matrix protein that regulates both bone development and phosphate metabolism. After glycosylation, an N-terminal fragment of DMP1 protein was identified as a new proteoglycan (DMP1-PG) in bone matrix. In vitro investigations showed that Ser(89) is the key glycosylation site in mouse DMP1. However, the specific role of DMP1 glycosylation is still not understood. In this study, a mutant DMP1 mouse model was developed in which the glycosylation site S(89) was substituted with G(89) (S89G-DMP1). The glycosylation level of DMP1 was down-regulated in the bone matrix of S89G-DMP1 mice. Compared with wild type mice, the long bones of S89G-DMP1 mice showed developmental changes, including the speed of bone remodeling and mineralization, the morphology and activities of osteocytes, and activities of both osteoblasts and osteoclasts. These findings indicate that glycosylation of DMP1 is a key posttranslational modification process during development and that DMP1-PG functions as an indispensable proteoglycan in osteogenesis.

  5. Effect of Serum and Oxygen Concentration on Gene Expression and Secretion of Paracrine Factors by Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Patrick Page

    2014-01-01

    Full Text Available Mesenchymal stem cells (MSC secrete paracrine factors that may exert a protective effect on the heart after coronary artery occlusion. This study was done to determine the effect of hypoxia and serum levels on the mRNA expression and secretion of paracrine factors. Mouse bone marrow MSC were cultured with 5% or 20% serum and in either normoxic (21% O2 or hypoxic (1% O2 conditions. Expression of mRNA for vascular endothelial growth factor (VEGF, monocyte chemotactic protein-1 (MCP-1, macrophage inflammatory protein-1α (MIP-1α, MIP-1β, and matrix metalloproteinase-2 (MMP-2 was determined by RT-qPCR. Secretion into the culture media was determined by ELISA. Hypoxia caused a reduction in gene expression for MCP-1 and an increase for VEGF (5% serum, MIP-1α, MIP-1β, and MMP-2. Serum reduction lowered gene expression for VEGF (normoxia, MCP-1 (hypoxia, MIP-1α (hypoxia, MIP-1β (hypoxia, and MMP-2 (hypoxia and increased gene expression for MMP-2 (normoxia. The level of secretion of these factors into the media generally paralleled gene expression with some exceptions. These data demonstrate that serum and oxygen levels have a significant effect on the gene expression and secretion of paracrine factors by MSC which will affect how MSC interact in vivo during myocardial ischemia.

  6. Using optical tweezers to examine the chemotactic force to a single inflammatory cell--eosinophil stimulated by chemoattractants prepared from Toxocara Canis larvae

    Science.gov (United States)

    Shih, Po-Chen; Su, Yi-Jr; Chen, Ke-Min; Jen, Lin-Ni; Liu, Cheng-tzu; Hsu, Long

    2005-08-01

    Granulocytes are a group of white blood cells belonging to the innate immune system in human and in murine in which eosinophils play an important role in worm infection-induced inflammation. The migration of these cells is well characterized and has been separated into four steps: rolling, adhesion, transendothelial migration, and chemotaxis, however, the physical characteristics of the chemotactic force to eosinophils from worm component remain largely unknown. Note that optical tweezers are featured in the manipulation of a single cell and the measurement of biological forces. Therefore, we propose to use optical tweezers to examine the chemotactic force to a eosinophil from a T. canis lavae preparation in terms of distance during the migration of eosinophil.

  7. Interleukin-8 is a major neutrophil chemotactic factor derived from cultured human gingival fibroblasts stimulated with interleukin-1 beta or tumor necrosis factor alpha.

    OpenAIRE

    Takashiba, S; Takigawa, M; Takahashi, K; Myokai, F; Nishimura, F.; Chihara, T.; Kurihara, H.; Nomura, Y.; Murayama, Y.

    1992-01-01

    Inflammatory mediators produced by cells in the gingiva have been implicated in the initiation and progression of periodontal disease, a common infectious disease. In this study, we examined the biological activity of neutrophil chemotactic factors and the kinetics of expression of interleukin-8 (IL-8) mRNA derived from normal gingival fibroblasts in response to inflammatory mediators in an in vitro model. Gingival fibroblasts stimulated by either recombinant human interleukin-1 beta or recom...

  8. Stromal-derived factor-1α/CXCL12-CXCR4 chemotactic pathway promotes perineural invasion in pancreatic cancer.

    Science.gov (United States)

    Xu, Qinhong; Wang, Zheng; Chen, Xin; Duan, Wanxing; Lei, Jianjun; Zong, Liang; Li, Xuqi; Sheng, Liang; Ma, Jiguang; Han, Liang; Li, Wei; Zhang, Lun; Guo, Kun; Ma, Zhenhua; Wu, Zheng; Wu, Erxi; Ma, Qingyong

    2015-03-10

    Perineural invasion (PNI) is considered as an alternative route for the metastatic spread of pancreatic cancer cells; however, the molecular changes leading to PNI are still poorly understood. In this study, we show that the CXCL12/CXCR4 axis plays a pivotal role in the neurotropism of pancreatic cancer cells to local peripheral nerves. Immunohistochemical staining results revealed that CXCR4 elevation correlated with PNI in 78 pancreatic cancer samples. Both in vitro and in vivo PNI models were applied to investigate the function of the CXCL12/CXCR4 signaling in PNI progression and pathogenesis. The results showed that the activation of the CXCL12/CXCR4 axis significantly increased pancreatic cancer cells invasion and promoted the outgrowth of the dorsal root ganglia. CXCL12 derived from the peripheral nerves stimulated the invasion and chemotactic migration of CXCR4-positive cancer cells in a paracrine manner, eventually leading to PNI. In vivo analyses revealed that the abrogation of the activated signaling inhibited tumor growth and invasion of the sciatic nerve toward the spinal cord. These data indicate that the CXCL12/CXCR4 axis may be a novel therapeutic target to prevent the perineural dissemination of pancreatic cancer.

  9. Inhibition of chemiluminescence and chemotactic activity of phagocytes in vitro by the extracts of selected medicinal plants.

    Science.gov (United States)

    Jantan, Ibrahim; Harun, Nurul Hikmah; Septama, Abdi Wira; Murad, Shahnaz; Mesaik, M A

    2011-04-01

    The methanol extracts of 20 selected medicinal plants were investigated for their effects on the respiratory burst of human whole blood, isolated human polymorphonuclear leukocytes (PMNs) and isolated mice macrophages using a luminol/lucigenin-based chemiluminescence assay. We also tested the effect of the extracts on chemotactic migration of PMNs using the Boyden chamber technique. The extracts of Curcuma domestica L., Phyllanthus amarus Schum & Thonn and C. xanthorrhiza Roxb. were the samples producing the strongest oxidative burst of PMNs with luminol-based chemiluminescence, with IC(50) values ranging from 0.5 to 0.7 μg/ml. For macrophage cells, the extracts which showed strong suppressive activity for luminol-based chemiluminescence were C. xanthorrhiza and Garcinia mangostana L. Among the extracts studied, C. mangga Valton & Vazsjip, Piper nigrum L. and Labisia pumila var. alata showed strong inhibitory activity on lucigenin-amplified oxidative burst of PMNs, with IC(50) values ranging from 0.9 to 1.5 μg/ml. The extracts of Zingiber officinale Rosc., Alpinia galangal (L.) Willd and Averrhoa bilimbi Linn showed strong inhibition on the chemotaxic migration of cells, with IC(50) values comparable to that of ibuprofen (1.5 μg/ml). The results suggest that some of these plants were able to modulate the innate immune response of phagocytes at different steps, emphasizing their potential as a source of new immunomodulatory agents. PMID:21184195

  10. A new SPH scheme to model transport of chemotactic bacteria in porous media at the continuum scale

    Science.gov (United States)

    Avesani, Diego; Bellin, Alberto; Dumbser, Michael; Chiogna, Gabriele

    2015-04-01

    As recently shown chemotaxis, i.e. the movement of microorganisms toward or away from the concentration gradient of a chemical species, could have a fundamental role in the transport of bacteria through saturated porous media. Chemotactic bacteria could enhance bioremediation by directing their own motions to residual contaminants in less conductive zones of aquifers. The aim of the present work is to develop a proper numerical scheme to define and to quantify the magnitude and the role of chemotaxis in the complex groundwater system framework. We present a new class of meshless Lagrangian particle methods based on the Smooth Particle Hydrodinamics (SPH) formulation of Vila & Ben Moussa, combined with a new Weighted Essentially Non-Oscillatory (WENO) reconstruction technique on moving point clouds in multiple space dimensions. The purpose of this new scheme is to fully exploit the advantages of SPH among traditional meshbased and meshfree schemes and to overcome its problems for modeling chemotaxis in porous media. We test the new scheme against analytical reference solutions and we show, under the assumption of complete mixing at the Darcy scale, that chemotaxis may significantly affect the quantification of field-scale bacterial distribution, therefore influencing reactive mixing and degradation of contaminants.

  11. Aurantio-obtusin stimulates chemotactic migration and differentiation of MC3T3-E1 osteoblast cells.

    Science.gov (United States)

    Vishnuprasad, Chethala N; Tsuchiya, Tomoko; Kanegasaki, Shiro; Kim, Joon Ho; Han, Sung Soo

    2014-05-01

    Osteoporosis is one of the major metabolic bone diseases and is among the most challenging noncommunicable diseases to treat. Although there is an increasing interest in identifying bioactive molecules for the prevention and management of osteoporosis, such studies principally focus only on differentiation and mineralization of osteoblasts or inhibition of osteoclast activity. Stimulation of osteoblast migration must be a promising osteoanabolic strategy for improved metabolic bone disease therapy. In this study, we show that an anthraquinone derivative, aurantio-obtusin, stimulated chemotactic migration of MC3T3-E1 osteoblast cells in a concentration-dependent manner. The use of a real-time chemotaxis analyzing system, TAXIScan, facilitated the evaluation of both velocity and directionality of osteoblast migration in response to the compound. Besides migration, the compound stimulated osteoblast differentiation and mineralization. Taken together, the data presented in this paper demonstrate that aurantio-obtusin is a promising osteoanabolic compound of natural origin with potential therapeutic applications in the prevention of osteoporosis and other metabolic bone diseases.

  12. CSF Biomarkers of Monocyte Activation and Chemotaxis correlate with Magnetic Resonance Spectroscopy Metabolites during Chronic HIV Disease

    Science.gov (United States)

    Anderson, Albert M.; Fennema-Notestine, Christine; Umlauf, Anya; Taylor, Michael J.; Clifford, David B.; Marra, Christina M.; Collier, Ann C.; Gelman, Benjamin B.; McArthur, Justin C.; McCutchan, J. Allen; Simpson, David M.; Morgello, Susan; Grant, Igor; Letendre, Scott L.

    2015-01-01

    Background HIV-associated neurocognitive disorders (HAND) persist despite combination antiretroviral therapy (cART), supporting the need to better understand HIV neuropathogenesis. Magnetic resonance spectroscopy (MRS) of the brain has demonstrated abnormalities in HIV-infected individuals despite cART. We examined the associations between MRS metabolites and selected cerebrospinal fluid (CSF) biomarkers reflecting monocyte/macrophage activation and chemotaxis. Methods A multicenter cross-sectional study involving five sites in the United States was conducted. The following CSF biomarkers were measured: soluble CD14 (sCD14), monocyte chemotactic protein 1 (MCP-1), interferon inducible protein 10 (IP-10), and stromal cell derived growth factor 1 alpha (SDF-1α). The following MRS metabolites were measured from basal ganglia (BG), frontal white matter (FWM) and frontal gray matter (FGM): N-acetyl-aspartate (NAA), Myo-inositol (MI), Choline (Cho), and Creatine (Cr). CSF biomarkers were compared to absolute MRS metabolites as well as metabolite/Cr ratios using linear regression. Results 83 HIV-infected individuals were included, 78% on cART and 37% with HAND. The most robust positive correlations were between MCP-1 and Cho in BG (R2 0.179, p<0.001) as well as MCP-1 and MI in FWM (R2 0.137, p=0.002). Higher Cr levels in FWM were associated with MCP-1 (R2 0. 075, p=0.01) and IP-10 (R2 0.106, p=0.003). Comparing biomarkers to MRS metabolite/Cr ratios impacted some relationships, e.g., higher sCD14 levels were associated with lower Cho/Cr ratios in FGM (R2 0.224, p<0.001), although higher MCP-1 levels remained associated with Cho/Cr in BG. Conclusion These findings provide evidence that monocyte activation and chemotaxis continue to contribute to HIV-associated brain abnormalities in cART-treated individuals. PMID:26069183

  13. Rabbit neutrophil chemotactic protein (NCP) activates both CXCR1 and CXCR2 and is the functional homologue for human CXCL6.

    Science.gov (United States)

    Catusse, Julie; Struyf, Sofie; Wuyts, Anja; Weyler, Myke; Loos, Tamara; Gijsbers, Klara; Gouwy, Mieke; Proost, Paul; Van Damme, Jo

    2004-11-15

    Neutrophil chemotactic protein (NCP) is a rabbit CXC chemokine with activating and chemotactic properties on neutrophilic granulocytes. Although its selective activity on neutrophils is demonstrated, its interactions with specific chemokine receptors are not defined. For further functional characterization, NCP was chemically synthesized and was found to be equipotent as natural NCP in neutrophil chemotaxis. To identify its human homologue, we separately expressed two potential rabbit NCP receptors (CXCR1 and CXCR2) in Jurkat cells. Pure synthetic NCP was equally efficient to promote chemotaxis through either rabbit CXCR1 or CXCR2. Moreover, chemotaxis assays on rabbit CXCR1 and CXCR2 transfectants showed that NCP uses the same receptors as interleukin-8 (IL-8), a major rabbit CXC chemokine, but not rabbit GROalpha, which only recognized CXCR2. In addition, specific inhibitors for CXCR1 or CXCR2 reduced rabbit neutrophil chemotaxis induced by NCP and rabbit IL-8. Furthermore, NCP and the structurally related human CXCR1/CXCR2 agonist CXCL6/GCP-2 (granulocyte chemotactic protein-2) cross-desensitized each other in intracellular calcium release assays on human neutrophils, further indicating that both chemokines share the same receptors. The inflammatory role of NCP was also evidenced by its potent granulocytosis inducing capacity in rabbits upon systemic administration. This study provides in vitro and in vivo evidences that NCP is the functional rabbit homologue for human CXCL6/GCP-2 rather than the most related CXCR2 agonist CXCL5/ENA-78 (epithelial cell-derived neutrophil activating peptide-78). It is concluded that the rabbit is a better model to study human neutrophil activation compared to mice, which lack CXCL8/IL-8.

  14. Glatiramer acetate (GA) prevents TNF-α-induced monocyte adhesion to primary endothelial cells through interfering with the NF-κB pathway

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Guoqian; Zhang, Xueyan; Su, Zhendong; Li, Xueqi, E-mail: xueqili075@yeah.net

    2015-01-30

    Highlights: • GA inhibited TNF-α-induced binding of monocytes to endothelial cells. • GA inhibited the induction of adhesion molecules MCP-1, VCAM-1 and E-selectin. • GA inhibits NF-κB p65 nuclear translocation and transcriptional activity. • GA inhibits TNF-α-induced IκBα degradation. - Abstract: Pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) is considered to be the major one contributing to the process of development of endothelial dysfunction. Exposure to TNF-α induces the expression of a number of proinflammatory chemokines, such as monocyte chemotactic protein-1 (MCP-1), and adhesion molecules, including vascular adhesion molecule-1 (VCAM-1) and E-selectin, which mediate the interaction of invading monocytes with vascular endothelial cells. Glatiramer acetate (GA) is a licensed clinical drug for treating patients suffering from multiple sclerosis (MS). The effects of GA in vascular disease have not shown before. In this study, we found that GA significantly inhibited TNF-α-induced binding of monocytes to endothelial cells. Mechanistically, we found that GA ameliorated the upregulation of MCP-1, VCAM-1, and E-selectin induced by TNF-α. Notably, this process is mediated by inhibiting the nuclear translocation and activation of NF-κB. Our results also indicate that GA pretreatment attenuates the up-regulation of COX-2 and iNOS. These data suggest that GA might have a potential benefit in therapeutic endothelial dysfunction related diseases.

  15. Effects of bone marrow-derived endothelial progenitor cell transplantation on vein microenvironment in a rat model of chronic thrombosis

    Institute of Scientific and Technical Information of China (English)

    LI Xiao-qiang; MENG Qing-you; WU Hao-rong

    2007-01-01

    Background Endothelial progenitor cells(EPCs) have been used in both experimental studies and clinical treatments of limb ischemia,as well as in the construction of engineered vascular tissue.The objective of this study was to investigate the effects of transplanted bone marrow-derived EPCs on the vein microenvironment in a rat model of chronic vein thrombosis.Methods Mononuclear cells were isolated from the bone marrow of immature rats by density gradient centrifugation,cultured,and then transplanted into experimentally induced thrombi into inferior vena cava through the femoral vein.Vascular endothelial growth factor(VEGF),angiopoietin-1(ANG-1) and monocyte chemotactic protein-1(MCP-1) mRNA and protein expression levels were measured by real-time quantitative polymerase chain reaction and Western blotting of thrombi and adjacent caval walls 28 days post-transplantation.Results Levels of VEGF,ANG-1,and MCP-1 mRNA in EPC-transplanted thrombi were 100%,230.7%,and 212.5% of levels detected in the sham-operated group(P<0.01),and 99.9%,215.4%,and 177.8% of levels detected in the experimental control group(P<0.01).VEGF,ANG-1 and MCP-1 protein levels exhibited a similar trend.Conclusions Transplanted bone marrow-derived EPCs appear to alter the vein microenvironment in experimentally induced chronic vein thrombosis by upregulating cytokines associated with thrombic organization and recanalization.

  16. Styrene induces an inflammatory response in human lung epithelial cells via oxidative stress and NF-κB activation

    International Nuclear Information System (INIS)

    Styrene is a volatile organic compound (VOC) that is widely used as a solvent in many industrial settings. Chronic exposure to styrene can result in irritation of the mucosa of the upper respiratory tract. Contact of styrene with epithelial cells stimulates the expression of a variety of inflammatory mediators, including the chemotactic cytokine monocyte chemoattractant protein-1 (MCP-1). To characterise the underlying mechanisms of the induction of inflammatory signals by styrene, we investigated the influence of this compound on the induction of oxidative stress and the activation of the nuclear factor-kappa B (NF-κB) signalling pathway in human lung epithelial cells (A549). The results demonstrate that styrene-induced MCP-1 expression, as well as the expression of the oxidative stress marker glutathione S-transferase (GST), is associated with a concentration dependent pattern of NF-κB activity. An inhibitor of NF-κB, IKK-NBD, and the anti-inflammatory antioxidant N-acetylcysteine (NAC) were both effective in suppressing styrene-induced MCP-1 secretion. In addition, NAC was capable of inhibiting the upregulation of GST expression. Our findings suggest that the activation of the NF-κB signalling pathway by styrene is mediated via a redox-sensitive mechanism

  17. Chlorella Protein Hydrolysate Attenuates Glucose Metabolic Disorder and Fatty Liver in High-fat Diet-induced Obese Mice.

    Science.gov (United States)

    Noguchi, Naoto; Yanagita, Teruyoshi; Rahman, Shaikh Mizanoor; Ando, Yotaro

    2016-07-01

    Chlorella (Parachlorella beijerinckii) powder is reported to show a preventive effect against metabolic syndromes such as arteriosclerosis, hyperlipidemia, and hypertension. Approximately 60% of the chlorella content is protein. In order to understand the role of chlorella protein, we prepared a chlorella protein hydrolysate (CPH) by protease treatment. Male C57BL/6 mice were divided into three groups: a normal diet group, high-fat diet (HFD) group, and high-fat diet supplemented with CPH (HFD+CPH) group. The CPH administration improved glucose intolerance, insulin sensitivity, and adipose tissue hypertrophy in the high-fat diet-fed mice. In addition, the HFD+CPH group had significantly decreased liver total cholesterol and triglyceride levels compared with those in the HFD group. Furthermore, the HFD+CPH group had a decreased level of monocyte chemotactic protein-1 (MCP-1) in serum and a lower MCP-1 mRNA expression level in adipose tissue compared with the HFD group. The present study suggests that chlorella protein hydrolysate can prevent a high-fat diet-induced glucose disorder and fatty liver by inhibiting adipocyte hypertrophy and reducing the MCP-1 protein and gene expression. PMID:27321121

  18. CSF biomarkers of monocyte activation and chemotaxis correlate with magnetic resonance spectroscopy metabolites during chronic HIV disease.

    Science.gov (United States)

    Anderson, Albert M; Fennema-Notestine, Christine; Umlauf, Anya; Taylor, Michael J; Clifford, David B; Marra, Christina M; Collier, Ann C; Gelman, Benjamin B; McArthur, Justin C; McCutchan, J Allen; Simpson, David M; Morgello, Susan; Grant, Igor; Letendre, Scott L

    2015-10-01

    Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) persist despite combination antiretroviral therapy (cART), supporting the need to better understand HIV neuropathogenesis. Magnetic resonance spectroscopy (MRS) of the brain has demonstrated abnormalities in HIV-infected individuals despite cART. We examined the associations between MRS metabolites and selected cerebrospinal fluid (CSF) biomarkers reflecting monocyte/macrophage activation and chemotaxis. A multicenter cross-sectional study involving five sites in the USA was conducted. The following CSF biomarkers were measured: soluble CD14 (sCD14), monocyte chemotactic protein-1 (MCP-1), interferon inducible protein 10 (IP-10), and stromal cell-derived growth factor 1 alpha (SDF-1α). The following MRS metabolites were measured from basal ganglia (BG), frontal white matter (FWM), and frontal gray matter (FGM): N-acetylaspartate (NAA), myo-inositol (MI), choline (Cho), and creatine (Cr). CSF biomarkers were compared to absolute MRS metabolites as well as metabolite/Cr ratios using linear regression. Eighty-three HIV-infected individuals were included, 78 % on cART and 37 % with HAND. The most robust positive correlations were between MCP-1 and Cho in BG (R (2) 0.179, p FGM (R (2) 0.224, p < 0.001), although higher MCP-1 levels remained associated with Cho/Cr in BG. These findings provide evidence that monocyte activation and chemotaxis continue to contribute to HIV-associated brain abnormalities in cART-treated individuals. PMID:26069183

  19. Signal regulatory protein alpha negatively regulates beta2 integrin-mediated monocyte adhesion, transendothelial migration and phagocytosis.

    Directory of Open Access Journals (Sweden)

    Dan-Qing Liu

    Full Text Available BACKGROUND: Signal regulate protein alpha (SIRPalpha is involved in many functional aspects of monocytes. Here we investigate the role of SIRPalpha in regulating beta(2 integrin-mediated monocyte adhesion, transendothelial migration (TEM and phagocytosis. METHODOLOGY/PRINCIPAL FINDINGS: THP-1 monocytes/macropahges treated with advanced glycation end products (AGEs resulted in a decrease of SIRPalpha expression but an increase of beta(2 integrin cell surface expression and beta(2 integrin-mediated adhesion to tumor necrosis factor-alpha (TNFalpha-stimulated human microvascular endothelial cell (HMEC-1 monolayers. In contrast, SIRPalpha overexpression in THP-1 cells showed a significant less monocyte chemotactic protein-1 (MCP-1-triggered cell surface expression of beta(2 integrins, in particular CD11b/CD18. SIRPalpha overexpression reduced beta(2 integrin-mediated firm adhesion of THP-1 cells to either TNFalpha-stimulated HMEC-1 monolayers or to immobilized intercellular adhesion molecule-1 (ICAM-1. SIRPalpha overexpression also reduced MCP-1-initiated migration of THP-1 cells across TNFalpha-stimulated HMEC-1 monolayers. Furthermore, beta(2 integrin-mediated THP-1 cell spreading and actin polymerization in response to MCP-1, and phagocytosis of bacteria were both inhibited by SIRPalpha overexpression. CONCLUSIONS/SIGNIFICANCE: SIRPalpha negatively regulates beta(2 integrin-mediated monocyte adhesion, transendothelial migration and phagocytosis, thus may serve as a critical molecule in preventing excessive activation and accumulation of monocytes in the arterial wall during early stage of atherosclerosis.

  20. Novel biochemical markers of psychosocial stress in women.

    Directory of Open Access Journals (Sweden)

    Marie Asberg

    Full Text Available BACKGROUND: Prolonged psychosocial stress is a condition assessed through self-reports. Here we aimed to identify biochemical markers for screening and early intervention in women. METHODS: Plasma concentrations of interleukin (IL 1-alpha, IL1-beta, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma (INF-gamma, tumor necrosis factor-alpha (TNF-alpha, monocyte chemotactic protein-1 (MCP-1, epidermal growth factor (EGF, vascular endothelial growth factor (VEGF, thyroid stimulating hormone (TSH, total tri-iodothyronine (TT3, total thyroxine (TT4, prolactin, and testosterone were measured in: 195 women on long-term sick-leave for a stress-related affective disorder, 45 women at risk for professional burnout, and 84 healthy women. RESULTS: We found significantly increased levels of MCP-1, VEGF and EGF in women exposed to prolonged psychosocial stress. Statistical analysis indicates that they independently associate with a significant risk for being classified as ill. CONCLUSIONS: MCP-1, EGF, and VEGF are potential markers for screening and early intervention in women under prolonged psychosocial stress.

  1. Critical chemotactic collapse

    Science.gov (United States)

    Lushnikov, Pavel M.

    2010-04-01

    A Keller-Segel model describes macroscopic dynamics of bacterial colonies and biological cells as well as dynamics of a gas of self-gravitating Brownian particles. Bacteria secret chemical which attracts other bacteria so that they move towards chemical gradient creating nonlocal attraction between bacteria. If bacterial (or Brownian particle) density exceeds a critical value then the density collapses (blows up) in a finite time which corresponds to bacterial aggregation or gravitational collapse. Collapse in the Keller-Segel model has striking qualitative similarities with a nonlinear Schrödinger equation including critical collapse in two dimensions and supercritical collapse in three dimensions. A self-similar solution near blow up point is studied in the critical two-dimensional case and it has a form of a rescaled steady state solution which contains a critical number of bacteria. Time dependence of scaling of that solution has square root scaling law with logarithmic modification.

  2. Critical chemotactic collapse

    OpenAIRE

    Lushnikov, Pavel M.

    2009-01-01

    A Keller-Segel model describes macroscopic dynamics of bacterial colonies and biological cells. Bacteria secret chemical which attracts other bacteria so that they move towards chemical gradient creating nonlocal attraction between bacteria. If bacterial density exceeds a critical value then the density collapses (blows up) in a finite time which corresponds to bacterial aggregation. Collapse in the Keller-Segel model has striking qualitative similarities with a nonlinear Schrodinger equation...

  3. Critical chemotactic collapse

    International Nuclear Information System (INIS)

    A Keller-Segel model describes macroscopic dynamics of bacterial colonies and biological cells as well as dynamics of a gas of self-gravitating Brownian particles. Bacteria secret chemical which attracts other bacteria so that they move towards chemical gradient creating nonlocal attraction between bacteria. If bacterial (or Brownian particle) density exceeds a critical value then the density collapses (blows up) in a finite time which corresponds to bacterial aggregation or gravitational collapse. Collapse in the Keller-Segel model has striking qualitative similarities with a nonlinear Schroedinger equation including critical collapse in two dimensions and supercritical collapse in three dimensions. A self-similar solution near blow up point is studied in the critical two-dimensional case and it has a form of a rescaled steady state solution which contains a critical number of bacteria. Time dependence of scaling of that solution has square root scaling law with logarithmic modification.

  4. Critical chemotactic collapse

    Energy Technology Data Exchange (ETDEWEB)

    Lushnikov, Pavel M., E-mail: plushnik@math.unm.ed [Department of Mathematics and Statistics, University of New Mexico, Albuquerque, NM 87131 (United States)

    2010-04-05

    A Keller-Segel model describes macroscopic dynamics of bacterial colonies and biological cells as well as dynamics of a gas of self-gravitating Brownian particles. Bacteria secret chemical which attracts other bacteria so that they move towards chemical gradient creating nonlocal attraction between bacteria. If bacterial (or Brownian particle) density exceeds a critical value then the density collapses (blows up) in a finite time which corresponds to bacterial aggregation or gravitational collapse. Collapse in the Keller-Segel model has striking qualitative similarities with a nonlinear Schroedinger equation including critical collapse in two dimensions and supercritical collapse in three dimensions. A self-similar solution near blow up point is studied in the critical two-dimensional case and it has a form of a rescaled steady state solution which contains a critical number of bacteria. Time dependence of scaling of that solution has square root scaling law with logarithmic modification.

  5. Cryoglobulins as Potential Triggers of Inflammation in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Andranik Chavushyan

    2013-01-01

    Full Text Available This case study aimed to investigate effects of type III cryoglobulins isolated from the blood of patients with schizophrenia on the production of proinflammatory cytokines interleukin(IL-1β, IL-6 and tumor necrosis factor-α (TNF-α, anti-inflammatory cytokine IL-10, and chemotactic cytokines IL-8 and monocyte chemoattractant protein-1 (MCP-1 by peripheral blood mononuclear cells (PBMCs. The experiments were performed in vitro using PBMCs healthy subjects and the blood of patients whit schizoprenia. The enzyme-linked immunosorbent assay and 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide assay were used upon study. The results obtained indicated significant increase (P<0.05 in IL-1β, IL-6, TNF-α, IL-8, and MCP-1 production by cultured PBMCs when incubating for 24 hours with cryoglobulins, beginning from 0.4 mg/mL. The gender difference does not affect the cryoglobulins-induced production of these cytokines by PBMCs. No influence of cryoglobulins on production of IL-10 by PBMCs was observed. Also, it was shown that cryoglobulins in concentration ≤4 mg/mL possessed no cytotoxic effect towards cultured PBMCs. Based upon the results obtained, we concluded that type III cryoglobulins are implicated in schizophrenia-associated alterations in the immune response through induction of the expression of proinflammatory and chemotactic cytokines by PBMCs.

  6. The expression of selenium-binding protein 1 is decreased in uterine leiomyoma

    Directory of Open Access Journals (Sweden)

    Quddus M Ruhul

    2010-12-01

    Full Text Available Abstract Background Selenium has been shown to inhibit cancer development and growth through the mediation of selenium-binding proteins. Decreased expression of selenium-binding protein 1 has been reported in cancers of the prostate, stomach, colon, and lungs. No information, however, is available concerning the roles of selenium-binding protein 1 in uterine leiomyoma. Methods Using Western Blot analysis and immunohistochemistry, we examined the expression of selenium-binding protein 1 in uterine leiomyoma and normal myometrium in 20 patients who had undergone hysterectomy for uterine leiomyoma. Results and Discussion The patient age ranged from 34 to 58 years with a mean of 44.3 years. Proliferative endometrium was seen in 8 patients, secretory endometrium in 7 patients, and atrophic endometrium in 5 patients. Two patients showed solitary leiomyoma, and eighteen patients revealed 2 to 5 tumors. Tumor size ranged from 1 to 15.5 cm with a mean of 4.3 cm. Both Western Blot analysis and immunohistochemistry showed a significant lower level of selenium-binding protein 1 in leiomyoma than in normal myometrium. Larger tumors had a tendency to show a lower level of selenium-binding protein 1 than smaller ones, but the difference did not reach a statistical significance. The expression of selenium-binding protein 1 was the same among patients with proliferative, secretory, and atrophic endometrium in either leiomyoma or normal myometrium. Also, we did not find a difference of selenium-binding protein 1 level between patients younger than 45 years and older patients in either leiomyoma or normal myometrium. Conclusions Decreased expression of selenium-binding protein 1 in uterine leiomyoma may indicate a role of the protein in tumorigenesis. Our findings may provide a basis for future studies concerning the molecular mechanisms of selenium-binding protein 1 in tumorigenesis as well as the possible use of selenium in prevention and treatment of uterine

  7. Expression of adhesion molecules, chemokines and matrix metallo- proteinases (MMPs) in viable and degenerating stage of Taenia solium metacestode in swine neurocysticercosis.

    Science.gov (United States)

    Singh, Satyendra K; Singh, Aloukick K; Prasad, Kashi N; Singh, Amrita; Singh, Avinash; Rai, Ravi P; Tripathi, Mukesh; Gupta, Rakesh K; Husain, Nuzhat

    2015-11-30

    Neurocysticercosis (NCC) is a parasitic infection of central nervous system (CNS). Expression of adhesion molecules, chemokines and matrix metalloproteinases (MMPs) were investigated on brain tissues surrounding viable (n=15) and degenerating cysticerci (n=15) of Taenia solium in swine by real-time RT-PCR and ELISA. Gelatin gel zymography was performed for MMPs activity. ICAM-1 (intercellular adhesion molecule-1), E-selectin, MIP-1α (macrophage inflammatory protein-1α), Eotaxin-1 and RANTES (regulated on activation, normal T cell expressed and secreted) were associated with degenerating cysticerci (cysts). However, VCAM-1 (vascular cell adhesion molecule-1), MCP-1 (monocyte chemotactic protein-1), MMP-2 and MMP-9 were associated with both viable and degenerating cysts. In conclusion, viable and degenerating cysticerci have different immune molecule profiles and role of these molecules in disease pathogenesis needs to be investigated. PMID:26412140

  8. Expression of adhesion molecules, chemokines and matrix metallo- proteinases (MMPs) in viable and degenerating stage of Taenia solium metacestode in swine neurocysticercosis.

    Science.gov (United States)

    Singh, Satyendra K; Singh, Aloukick K; Prasad, Kashi N; Singh, Amrita; Singh, Avinash; Rai, Ravi P; Tripathi, Mukesh; Gupta, Rakesh K; Husain, Nuzhat

    2015-11-30

    Neurocysticercosis (NCC) is a parasitic infection of central nervous system (CNS). Expression of adhesion molecules, chemokines and matrix metalloproteinases (MMPs) were investigated on brain tissues surrounding viable (n=15) and degenerating cysticerci (n=15) of Taenia solium in swine by real-time RT-PCR and ELISA. Gelatin gel zymography was performed for MMPs activity. ICAM-1 (intercellular adhesion molecule-1), E-selectin, MIP-1α (macrophage inflammatory protein-1α), Eotaxin-1 and RANTES (regulated on activation, normal T cell expressed and secreted) were associated with degenerating cysticerci (cysts). However, VCAM-1 (vascular cell adhesion molecule-1), MCP-1 (monocyte chemotactic protein-1), MMP-2 and MMP-9 were associated with both viable and degenerating cysts. In conclusion, viable and degenerating cysticerci have different immune molecule profiles and role of these molecules in disease pathogenesis needs to be investigated.

  9. X-box-binding protein 1-modified neural stem cells for treatment of Parkinson's disease.

    Science.gov (United States)

    Si, Lihui; Xu, Tianmin; Wang, Fengzhang; Liu, Qun; Cui, Manhua

    2012-04-01

    X-box-binding protein 1-transfected neural stem cells were transplanted into the right lateral ventricles of rats with rotenone-induced Parkinson's disease. The survival capacities and differentiation rates of cells expressing the dopaminergic marker tyrosine hydroxylase were higher in X-box-binding protein 1-transfected neural stem cells compared to non-transfected cells. Moreover, dopamine and 3,4-dihydroxyphenylacetic acid levels in the substantia nigra were significantly increased, α-synuclein expression was decreased, and neurological behaviors were significantly ameliorated in rats following transplantation of X-box-binding protein 1-transfected neural stem cells. These results indicate that transplantation of X-box-binding protein 1-transfected neural stem cells can promote stem cell survival and differentiation into dopaminergic neurons, increase dopamine and 3,4-dihydroxyphenylacetic acid levels, reduce α-synuclein aggregation in the substantia nigra, and improve the symptoms of Parkinson's disease in rats.

  10. X-box-binding protein 1-modified neural stem cells for treatment of Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    Lihui Si; Tianmin Xu; Fengzhang Wang; Qun Liu; Manhua Cui

    2012-01-01

    X-box-binding protein 1-transfected neural stem cells were transplanted into the right lateral ventricles of rats with rotenone-induced Parkinson's disease. The survival capacities and differentiation rates of cells expressing the dopaminergic marker tyrosine hydroxylase were higher in X-box-binding protein 1-transfected neural stem cells compared to non-transfected cells. Moreover, dopamine and 3,4-dihydroxyphenylacetic acid levels in the substantia nigra were significantly increased, α-synuclein expression was decreased, and neurological behaviors were significantly ameliorated in rats following transplantation of X-box-binding protein 1-transfected neural stem cells. These results indicate that transplantation of X-box-binding protein 1-transfected neural stem cells can promote stem cell survival and differentiation into dopaminergic neurons, increase dopamine and 3,4-dihydroxyphenylacetic acid levels, reduce α-synuclein aggregation in the substantia nigra, and improve the symptoms of Parkinson's disease in rats.

  11. Expression of monocyte chemoattractant protein-1 in the pancreas of mice

    Institute of Scientific and Technical Information of China (English)

    LI Dong; ZHU Su-wen; LIU Dong-juan; LIU Guo-liang; SHAN Zhong-yan

    2005-01-01

    Background Type 1 diabetes has been recognized as an organ specific autoimmune disease owing to the immune destruction of pancreatic islet β cells in genetically susceptible individuals.In both human and rodent models of type 1 diabetes, such as nonobese diabetic (NOD) mice, biobreeding rats, the disease has a distinct stage characterized by immune cells infiltrating in the pancreas (insulitis).The major populations of infiltrating cells are macrophages and T lymphocytes.Therefore, immune cell infiltration of pancreatic islets may be a crucial step in the pathogenesis of type 1 diabetes.Monocyte chemoattractant protein-1 can specifically attract monocytes in vivo.Interferon induced protein-10 has chemoattractant effects on the activated lymphocytes.In this study, we analysed the expression of monocyte chemoattractant protein-1 in the pancreas of mice and interferon inducible protein-10 mRNA in the pancreas of NOD mice, and discussed their possible role in the pathogenesis of type 1 diabetes.Methods The immunohistochemical method and immunoelectronmicroscopy were used to evaluate the expression of monocyte chemoattractant protein-1 in the pancreas of NOD mice and BALB/c mice.RT-PCR was used to evaluate the expression of monocyte chemoattractant protein-1 and interferon inducible protein mRNA in NOD mice.Results Monocyte chemoattractant protein-1 was positive in the pancreas of NOD mice, whereas negative in the pancreas of BALB/C mice.RT-PCR showed that monocyte chemoattractant protein-1 and interferon inducible protein-10 mRNA could be found in the pancreas of NOD mice.Immunoelectronmicroscopy demonstrated that monocyte chemoattractant protein-1 was produced by β cells and stored in the cytoplasm of the cells.Conclusions Pancreatic islet β cells produce monocyte chemoattractantprotein-1 in NOD mice.Monocyte chemoattractant protein-1 may play an important part in the pathogenesis of type 1 diabetes by attracting monocytes/macrophages to infiltrate pancreatic

  12. Delivery of platelet-derived growth factor as a chemotactic factor for mesenchymal stem cells by bone-mimetic electrospun scaffolds.

    Directory of Open Access Journals (Sweden)

    Matthew C Phipps

    Full Text Available The recruitment of mesenchymal stem cells (MSCs is a vital step in the bone healing process, and hence the functionalization of osteogenic biomaterials with chemotactic factors constitutes an important effort in the tissue engineering field. Previously we determined that bone-mimetic electrospun scaffolds composed of polycaprolactone, collagen I and nanohydroxyapatite (PCL/col/HA supported greater MSC adhesion, proliferation and activation of integrin-related signaling cascades than scaffolds composed of PCL or collagen I alone. In the current study we investigated the capacity of bone-mimetic scaffolds to serve as carriers for delivery of an MSC chemotactic factor. In initial studies, we compared MSC chemotaxis toward a variety of molecules including PDGF-AB, PDGF-BB, BMP2, and a mixture of the chemokines SDF-1α, CXCL16, MIP-1α, MIP-1β, and RANTES. Transwell migration assays indicated that, of these factors, PDGF-BB was the most effective in stimulating MSC migration. We next evaluated the capacity of PCL/col/HA scaffolds, compared with PCL scaffolds, to adsorb and release PDGF-BB. We found that significantly more PDGF- BB was adsorbed to, and subsequently released from, PCL/col/HA scaffolds, with sustained release extending over an 8-week interval. The PDGF-BB released was chemotactically active in transwell migration assays, indicating that bioactivity was not diminished by adsorption to the biomaterial. Complementing these studies, we developed a new type of migration assay in which the PDGF-BB-coated bone-mimetic substrates were placed 1.5 cm away from the cell migration front. These experiments confirmed the ability of PDGF-BB-coated PCL/col/HA scaffolds to induce significant MSC chemotaxis under more stringent conditions than standard types of migration assays. Our collective results substantiate the efficacy of PDGF-BB in stimulating MSC recruitment, and further show that the incorporation of native bone molecules, collagen I and nano

  13. Tracking Chemotactic Migration of a Genetically Engineered Bacterium in the Presence of Constructed Nutrient Gradients Within a Sandy Aquifer in Cape Cod, Massachusetts

    Science.gov (United States)

    Harvey, R. W.; Ford, R. M.; Metge, D. W.; Wang, M.; Toepfer, A. A.; McGowan, S. B.

    2008-05-01

    Due to our increasing dependence upon groundwater resources, there is a growing need to remediate shallow aquifers contaminated with chlorinated solvents. Often, trichloroethene (TCE) travels into zones of low permeability thereby making removal difficult by traditional pump-and-treat technologies. In addition, degradation of TCE by native microbial communities can result in buildup of highly toxic intermediates such as vinyl chloride. Bioaugmentation, involving addition of specialized bacterial consortia to an aquifer, can facilitate more complete degradation into harmless byproducts. Also, it is believed that chemotaxis, the ability of bacteria to swim towards higher concentrations of a chemical perceived as beneficial to survival, may expedite movement of introduced bacteria to where they are needed. However, there is no quantitative information about chemotaxis at the field scale and the evidence for bacterial chemotaxis during bioaugmentation has been largely anecdotal. In this study, the chemotactic migration of the bacterium, Pseudomonas stutzeri in a TCE-contaminated, sand- and-gravel aquifer in Cape Cod, Massachusetts was measured. P. stutzeri is known to denitrify as well as degrade a variety of aromatic and chlorinated solvents and is often advocated as a candidate for bioaugmentation. This bacterium was genetically engineered to be resistant to ampicillin and produce blue- fluorescing protein (BFP) in order to facilitate maintaining the bacteria in pure culture and later to track them in the environment. The study involved a natural-gradient injection and recovery test in which vertical gradients of an electron donor (acetate) and acceptor (nitrate) were created within the sandy aquifer sediments above an amendment of the genetically engineered P. stutzeri. The bacteria, nitrate, and acetate were allowed to be advected with the natural flow of groundwater past close-interval, multi-level samplers that were installed downgradient from the points of

  14. Lower concentrations of chemotactic cytokines and soluble innate factors in the lower female genital tract associated with the use of injectable hormonal contraceptive.

    Science.gov (United States)

    Ngcapu, Sinaye; Masson, Lindi; Sibeko, Sengeziwe; Werner, Lise; McKinnon, Lyle R; Mlisana, Koleka; Shey, Muki; Samsunder, Natasha; Karim, Salim Abdool; Karim, Quarraisha Abdool; Passmore, Jo-Ann S

    2015-08-01

    Progesterone-based injectable hormonal contraceptives (HCs) potentially modulate genital barrier integrity and regulate the innate immune environment in the female genital tract, thereby enhancing the risk of STIs or HIV infection. We investigated the effects of injectable HC use on concentrations of inflammatory cytokines and other soluble factors associated with genital epithelial repair and integrity. The concentrations of 42 inflammatory, regulatory, adaptive growth factors and hematopoietic cytokines, five matrix metalloproteinases (MMPs), and four tissue inhibitors of metalloproteinases (TIMPs) were measured in cervicovaginal lavages (CVLs) from 64 HIV-negative women using injectable HCs and 64 control women not using any HCs, in a matched case-control study. There were no differences between groups in the prevalence of bacterial vaginosis (BV; Nugent score ≥7), or common sexually transmitted infections (STIs). In multivariate analyses adjusting for condom use, sex work status, marital status, BV and STIs, median concentrations of chemokines (eotaxin, MCP-1, MDC), adaptive cytokines (IL-15), growth factors (PDGF-AA) and a metalloproteinase (TIMP-2) were significantly lower in CVLs from women using injectable HCs than controls. In addition, the pro-inflammatory cytokine IL-12p40 and the chemokine fractalkine were less likely to have detectable levels in women using injectable HCs compared with those not using HCs. We conclude that injectable HC use was broadly associated with an immunosuppressive female genital tract innate immune profile. While the relationship between injectable HC use and STI or HIV risk is yet to be resolved, our data suggest that the effects of injectable HCs were similar in STI-positive and STI-negative participants.

  15. Obese Mexican American children have elevated MCP-1, TNF-alpha, monocyte concentration, and dyslipidemia

    Science.gov (United States)

    Obesity is an independent risk factor for chronic disease. The prevalence of obesity is especially high among Mexican American children. Peripheral blood monocytes are altered with obesity contributing to elevated systemic inflammation and increased risk of chronic disease. In addition, obesity alte...

  16. Aging and serum MCP-1 are associated with gut microbiome composition in a murine model

    OpenAIRE

    Conley, Melissa N.; Wong, Carmen P.; Duyck, Kyle M.; Hord, Norman; Ho, Emily; Sharpton, Thomas J

    2016-01-01

    Introduction. Age is the primary risk factor for major human chronic diseases, including cardiovascular disorders, cancer, type 2 diabetes, and neurodegenerative diseases. Chronic, low-grade, systemic inflammation is associated with aging and the progression of immunosenescence. Immunosenescence may play an important role in the development of age-related chronic disease and the widely observed phenomenon of increased production of inflammatory mediators that accompany this process, referred ...

  17. Regulating MCP-1 Diffusion in Affinity Hydrogels for Enhancing Immuno-isolation

    OpenAIRE

    Lin, Chien-Chi; Boyer, Patrick D.; Aimetti, Alex A.; Anseth, Kristi S.

    2009-01-01

    Delivering cells using semi-permeable hydrogels is becoming an increasingly important direction in cell based therapies and regenerative medicine applications. Synthetic hydrogels have been functionalized with bioactive motifs to render otherwise inert polymer networks responsive. However, little effort has been focused on creating immuno-isolating materials capable of retarding the transport of small antigenic molecules secreted from the cells delivered with the synthetic carriers. Toward th...

  18. Pneumocystis carinii major surface glycoprotein induces interleukin-8 and monocyte chemoattractant protein-1 release from a human alveolar epithelial cell line

    DEFF Research Database (Denmark)

    Benfield, T L; Lundgren, Bettina; Shelhamer, J H;

    1999-01-01

    experiments showed increases in IL-8 release at 4 h, 8 h and 24 h compared with control cultures (all P minor (13%) dose- and time-related increase in MCP-1 release at 24 h (P = 0.02). Co-incubation of MSG with mannan or beta-glucan decreased IL-8 release by 48% and 42% respectively......, suggesting that MSG stimulates A549 cells in part through carbohydrate moieties. Dexamethasone significantly inhibited MSG-induced IL-8 release in concentrations of 10-6-10-8 mol L-1 compared with control experiments (P protection assays for steady-state IL-8 mRNA showed that increases...

  19. Alterations in expression levels of deafness dystonia protein 1 affect mitochondrial morphology

    DEFF Research Database (Denmark)

    Engl, Gertraud; Florian, Stefan; Tranebjærg, Lisbeth;

    2012-01-01

    Deafness-Dystonia-Optic Neuropathy (DDON) Syndrome is a rare X-linked progressive neurodegenerative disorder resulting from mutations in the TIMM8A gene encoding for the deafness dystonia protein 1 (DDP1). Despite important progress in identifying and characterizing novel mutations in this gene...

  20. Expression of Plasmodium falciparum erythrocyte membrane protein 1 in experimentally infected humans

    DEFF Research Database (Denmark)

    Lavstsen, Thomas; Magistrado, Pamela; Hermsen, Cornelus C;

    2005-01-01

    -encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family, which is expressed on the surface of infected erythrocytes where it mediates binding to endothelial receptors. Thus, severe malaria may be caused by parasites expressing PfEMP1 variants that afford parasites optimal sequestration in...

  1. Role of macrophage inflammatory protein-1alpha in T-cell-mediated immunity to viral infection

    DEFF Research Database (Denmark)

    Madsen, Andreas N; Nansen, Anneline; Christensen, Jan P;

    2003-01-01

    The immune response to lymphocytic choriomeningitis virus in mice lacking macrophage inflammatory protein-1alpha (MIP-1alpha) was evaluated. Generation of virus-specific effector T cells is unimpaired in MIP-1alpha-deficient mice. Furthermore, MIP-1alpha is not required for T-cell-mediated virus...

  2. X-ray repair cross complementing protein 1 in base excision repair

    DEFF Research Database (Denmark)

    Hanssen-Bauer, Audun; Solvang-Garten, Karin; Akbari, Mansour;

    2012-01-01

    X-ray Repair Cross Complementing protein 1 (XRCC1) acts as a scaffolding protein in the converging base excision repair (BER) and single strand break repair (SSBR) pathways. XRCC1 also interacts with itself and rapidly accumulates at sites of DNA damage. XRCC1 can thus mediate the assembly of large...

  3. PTPRT regulates the interaction of Syntaxin-binding protein 1 with Syntaxin 1 through dephosphorylation of specific tyrosine residue

    Energy Technology Data Exchange (ETDEWEB)

    Lim, So-Hee; Moon, Jeonghee [Biomedical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Lee, Myungkyu [Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Lee, Jae-Ran, E-mail: leejr@kribb.re.kr [Biomedical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of)

    2013-09-13

    Highlights: •PTPRT is a brain-specific, expressed, protein tyrosine phosphatase. •PTPRT regulated the interaction of Syntaxin-binding protein 1 with Syntaxin 1. •PTPRT dephosphorylated the specific tyrosine residue of Syntaxin-binding protein 1. •Dephosphorylation of Syntaxin-binding protein 1 enhanced the interaction with Syntaxin 1. •PTPRT appears to regulate the fusion of synaptic vesicle through dephosphorylation. -- Abstract: PTPRT (protein tyrosine phosphatase receptor T), a brain-specific tyrosine phosphatase, has been found to regulate synaptic formation and development of hippocampal neurons, but its regulation mechanism is not yet fully understood. Here, Syntaxin-binding protein 1, a key component of synaptic vesicle fusion machinery, was identified as a possible interaction partner and an endogenous substrate of PTPRT. PTPRT interacted with Syntaxin-binding protein 1 in rat synaptosome, and co-localized with Syntaxin-binding protein 1 in cultured hippocampal neurons. PTPRT dephosphorylated tyrosine 145 located around the linker between domain 1 and 2 of Syntaxin-binding protein 1. Syntaxin-binding protein 1 directly binds to Syntaxin 1, a t-SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein, and plays a role as catalysts of SNARE complex formation. Syntaxin-binding protein 1 mutant mimicking non-phosphorylation (Y145F) enhanced the interaction with Syntaxin 1 compared to wild type, and therefore, dephosphorylation of Syntaxin-binding protein 1 appeared to be important for SNARE-complex formation. In conclusion, PTPRT could regulate the interaction of Syntaxin-binding protein 1 with Syntaxin 1, and as a result, the synaptic vesicle fusion appeared to be controlled through dephosphorylation of Syntaxin-binding protein 1.

  4. Behavioral Deficits Are Accompanied by Immunological and Neurochemical Changes in a Mouse Model for Neuropsychiatric Lupus (NP-SLE)

    DEFF Research Database (Denmark)

    Li, Yan; Eskelund, Amanda; Zhou, H;

    2015-01-01

    Neuropsychiatric symptoms of systemic lupus erythematosus (NP-SLE) have been understudied compared to end-organ failure and peripheral pathology. Neuropsychiatric symptoms, particularly affective and cognitive indications, may be among the earliest manifestations of SLE. Among the potential...... pathophysiological mechanisms responsible for NP-SLE are increased peripheral pro-inflammatory cytokines, subsequent induction of indoleamine-2,3-dioxygenase (IDO) and activation of the kynurenine pathway. In the MRL/MpJ-Faslpr (MRL/lpr) murine model of lupus, depression-like behavior and cognitive dysfunction......), monocyte chemotactic protein 1, 3 and 5 (MCP-1/CCL2, MCP-3/CCL7, MCP-5/CCL12), vascular cell adhesion molecule 1 (VCAM-1), lymphotactin and interferon γ (IFN-γ)) were increased in MRL/lpr mice. In cortex and hippocampus, MRL/lpr mice had increased levels of kynurenine pathway metabolites (kynurenine, 3...

  5. Cytokine and nitric oxide levels in patients with sepsis--temporal evolvement and relation to platelet mitochondrial respiratory function

    DEFF Research Database (Denmark)

    Sjövall, Fredrik; Morota, Saori; Frostner, Eleonor Åsander;

    2014-01-01

    the correlation between observed changes in platelet mitochondrial respiration and a set of pro- and anti-inflammatory cytokines as well as NO plasma levels in patients with sepsis. METHODS AND RESULTS: Platelet mitochondrial respiration and levels of TNFα, MCP-1 (monocyte chemotactic protein-1), INFγ (interferon......-γ), IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10 and IL-17 and NO were analyzed in 38 patients with severe sepsis or septic shock at three time points during one week following admission to the ICU. Citrate synthase, mitochondrial DNA and cytochrome c were measured as markers of cellular mitochondrial content....... All mitochondrial respiratory states increased over the week analyzed (prespiration on day 6-7 (p = 0.02, r2 = 0.22) and was also higher in non-survivors compared to survivors on day 3-4 and day 6-7 (p = 0.03 respectively). Neither NO nor any...

  6. Bigenomic transcriptional regulation of all thirteen cytochrome c oxidase subunit genes by specificity protein 1

    OpenAIRE

    Dhar, Shilpa S.; Johar, Kaid; Wong-Riley, Margaret T. T.

    2013-01-01

    Cytochrome c oxidase (COX) is one of only four known bigenomic proteins, with three mitochondria-encoded subunits and 10 nucleus-encoded ones derived from nine different chromosomes. The mechanism of regulating this multi-subunit, bigenomic enzyme is not fully understood. We hypothesize that specificity protein 1 (Sp1) functionally regulates the 10 nucleus-encoded COX subunit genes directly and the three mitochondrial COX subunit genes indirectly by regulating mitochondrial transcription fact...

  7. Immunocytochemical localization of microtubule-associated protein 1 in rat cerebellum using monoclonal antibodies

    OpenAIRE

    1984-01-01

    Immunohistochemical staining with monoclonal antibodies showed that microtubule-associated protein 1 (MAP1) has a restricted cellular distribution in the rat cerebellum. Anti-MAP1 staining was found only in neurons, where it was much stronger in dendrites than in axons. There were striking variations in the apparent concentration of MAP1 in different classes of neurons. Purkinje cells were the most strongly labeled, while granule cell neurons gave a faint, threshold-level reaction with the an...

  8. Specificity Protein 1 Expression Contributes to Bcl-w-Induced Aggressiveness in Glioblastoma Multiforme

    OpenAIRE

    Lee, Woo Sang; Kwon, Junhye; Yun, Dong Ho; Lee, Young Nam; Woo, Eun Young; Park, Myung-Jin; Lee, Jae-Seon; Han, Young-Hoon; Bae, In Hwa

    2014-01-01

    We already had reported that Bcl-w promotes invasion or migration in gastric cancer cells and glioblastoma multiforme (GBM) by activating matrix metalloproteinase-2 (MMP-2) via specificity protein 1 (Sp1) or β-cateinin, respectively. High expression of Bcl-w also has been reported in GBM which is the most common malignant brain tumor and exhibits aggressive and invasive behavior. These reports propose that Bcl-w-induced signaling is strongly associated with aggressive characteristic of GBM. W...

  9. Dickkopf-related protein 1 inhibits the WNT signaling pathway and improves pig oocyte maturation.

    Directory of Open Access Journals (Sweden)

    Lee D Spate

    Full Text Available The ability to mature oocytes in vitro provides a tool for creating embryos by parthenogenesis, fertilization, and cloning. Unfortunately the quality of oocytes matured in vitro falls behind that of in vivo matured oocytes. To address this difference, transcriptional profiling by deep sequencing was conducted on pig oocytes that were either matured in vitro or in vivo. Alignment of over 18 million reads identified 1,316 transcripts that were differentially represented. One pathway that was overrepresented in the oocytes matured in vitro was for Wingless-type MMTV integration site (WNT signaling. In an attempt to inhibit the WNT pathway, Dickkopf-related protein 1 was added to the in vitro maturation medium. Addition of Dickkopf-related protein 1 improved the percentage of oocytes that matured to the metaphase II stage, increased the number of nuclei in the resulting blastocyst stage embryos, and reduced the amount of disheveled segment polarity protein 1 protein in oocytes. It is concluded that transcriptional profiling is a powerful method for detecting differences between in vitro and in vivo matured oocytes, and that the WNT signaling pathway is important for proper oocyte maturation.

  10. Osteopontin, a chemotactic protein with cytokine-like properties, is up-regulated in muscle injury caused by Bothrops lanceolatus (fer-de-lance) snake venom.

    Science.gov (United States)

    Barbosa-Souza, Valéria; Contin, Daniel Kiss; Filho, Waldemar Bonventi; de Araújo, Albetiza Lôbo; Irazusta, Silvia Pierre; da Cruz-Höfling, Maria Alice

    2011-10-01

    Osteopontin (OPN) is a chemotactic, adhesive protein whose receptors include some integrins and matrix proteins known to have role in inflammatory and repair processes. We examined the time course of OPN expression at acute and chronic stages after intramuscular injection of Bothrops lanceolatus venom in rats. Additionally, we examined the expression of CD68 (a marker for phagocytic macrophages) and the myogenic factors, myoD and myogenin. There was a biphasic upregulation of OPN (6-48 h and 3-14 days post-venom), i.e., during acute inflammation and myogenic cell proliferation and differentiation phases. OPN was detected in CD68 + macrophages, fibroblasts, normal and damaged myofibers, myoblasts and myotubes. Myogenin was expressed in the cytoplasm (atypical pattern) and nucleus of myoblasts and myotubes from 18 h to 7 days, after which it was expressed only in nuclei. Macrophage numbers, OPN and myogenin expression were still elevated at 7, 14 and 7 days. At 3 days, when OPN achieved the peak, some clusters of myoblasts were within regions of intense collagen deposition. Fibrosis may represent limitation for repairing processes and may explain the small diameter of regenerated fibers at 21 days post-venom. The expression of OPN in the course of venom-induced damage and regeneration suggests stages-specific mediation role along the whole process. PMID:21839764

  11. Impaired LDL Receptor-Related Protein 1 Translocation Correlates with Improved Dyslipidemia and Atherosclerosis in apoE-Deficient Mice

    DEFF Research Database (Denmark)

    Gordts, Philip L S M; Bartelt, Alexander; Nilsson, Stefan K;

    2012-01-01

    Determination of the in vivo significance of LDL receptor-related protein 1 (LRP1) dysfunction on lipid metabolism and atherosclerosis development in absence of its main ligand apoE.......Determination of the in vivo significance of LDL receptor-related protein 1 (LRP1) dysfunction on lipid metabolism and atherosclerosis development in absence of its main ligand apoE....

  12. Speciifc effects of c-Jun NH2-terminal kinase-interacting protein 1 in neuronal axons

    Institute of Scientific and Technical Information of China (English)

    Shu Tang; Qiang Wen; Xiao-jian Zhang; Quan-cheng Kan

    2016-01-01

    c-Jun NH2-terminal kinase (JNK)-interacting protein 3 plays an important role in brain-derived neurotrophic factor/tropomyosin-related kinase B (TrkB) anterograde axonal transport. It remains unclear whether JNK-interacting protein 1 mediates similar effects, or whether JNK-interacting protein 1 affects the regulation of TrkB anterograde axonal transport. In this study, we isolated rat embryonic hippocampus and cultured hippocampal neuronsin vitro. Coimmunoprecipitation results demonstrated that JNK-interacting protein 1 formed TrkB com-plexesin vitro andin vivo. Immunocytochemistry results showed that when JNK-interacting protein 1 was highly expressed, the distribution of TrkB gradually increased in axon terminals. However, the distribution of TrkB reduced in axon terminals after knocking out JNK-interact-ing protein 1. In addition, there were differences in distribution of TrkB after JNK-interacting protein 1 was knocked out compared with not. However, knockout of JNK-interacting protein 1 did not affect the distribution of TrkB in dendrites. These ifndings conifrm that JNK-inter-acting protein 1 can interact with TrkB in neuronal cells, and can regulate the transport of TrkB in axons, but not in dendrites.

  13. Hydrogen peroxide activates activator protein-1 and mitogen-activated protein kinases in pancreatic stellate cells.

    Science.gov (United States)

    Kikuta, Kazuhiro; Masamune, Atsushi; Satoh, Masahiro; Suzuki, Noriaki; Satoh, Kennichi; Shimosegawa, Tooru

    2006-10-01

    Activated pancreatic stellate cells (PSCs) are implicated in the pathogenesis of pancreatic inflammation and fibrosis, where oxidative stress is thought to play a key role. Reactive oxygen species such as hydrogen peroxide (H(2)O(2)) may act as a second messenger to mediate the actions of growth factors and cytokines. But the role of reactive oxygen species in the activation and regulation of cell functions in PSCs remains largely unknown. We here examined the effects of H(2)O(2) on the activation of signal transduction pathways and cell functions in PSCs. PSCs were isolated from the pancreas of male Wistar rats, and used in their culture-activated, myofibroblast-like phenotype unless otherwise stated. Activation of transcription factors was examined by electrophoretic mobility shift assay and luciferase assay. Activation of mitogen-activated protein (MAP) kinases was assessed by Western blotting using anti-phosphospecific antibodies. The effects of H(2)O(2) on proliferation, alpha(1)(I)procollagen gene expression, and monocyte chemoattractant protein-1 production were evaluated. The effect of H(2)O(2) on the transformation of freshly isolated PSCs in culture was also assessed. H(2)O(2) at non-cytotoxic concentrations (up to 100 microM) induced oxidative stress in PSCs. H(2)O(2) activated activator protein-1, but not nuclear factor kappaB. In addition, H(2)O(2) activated three classes of MAP kinases: extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 MAP kinase. H(2)O(2) induced alpha(1)(I)procollagen gene expression but did not induce proliferation or monocyte chemoattractant protein-1 production. H(2)O(2) did not initiate the transformation of freshly isolated PSCs to myofibroblast-like phenotype. Specific activation of these signal transduction pathways and collagen gene expression by H(2)O(2) may play a role in the pathogenesis of pancreatic fibrosis.

  14. Mice lacking multidrug resistance protein 1a show altered dopaminergic responses to methylenedioxymethamphetamine (MDMA) in striatum

    OpenAIRE

    Scheidweiler, Karl B.; Ladenheim, Bruce; Cadet, Jean Lud; Huestis, Marilyn A.

    2009-01-01

    Multidrug resistance protein 1a (MDR1a) potentiated methylenedioxymethamphetamine (MDMA)-induced decreases of dopamine (DA) and dopamine transport protein in mouse brain one week after MDMA administration. In the present study, we examined if mdr1a wild-type (mdr1a +/+) and knock-out (mdr1a −/−) mice differentially handle the acute effects of MDMA on the nigrostriatal DA system 0–24 h following a single drug injection. 3-way ANOVA revealed significant 2-way interactions of strain X time (F5,1...

  15. Inactivation of fatty acid transport protein 1 prevents fat-induced insulin resistance in skeletal muscle

    OpenAIRE

    Jason K Kim; Gimeno, Ruth E.; Higashimori, Takamasa; Kim, Hyo-Jeong; Choi, Hyejeong; Punreddy, Sandhya; Mozell, Robin L.; TAN, GUO; Stricker-Krongrad, Alain; Hirsch, David J.; Fillmore, Jonathan J.; Liu, Zhen-Xiang; Dong, Jianying; Cline, Gary; Stahl, Andreas

    2004-01-01

    Insulin resistance in skeletal muscle plays a major role in the development of type 2 diabetes and may be causally associated with increases in intramuscular fatty acid metabolites. Fatty acid transport protein 1 (FATP1) is an acyl-CoA synthetase highly expressed in skeletal muscle and modulates fatty acid uptake and metabolism by converting fatty acids into fatty acyl-CoA. To investigate the role of FATP1 in glucose homeostasis and in the pathogenesis of insulin resistance, we examined the e...

  16. GPCR kinase 2 interacting protein 1 (GIT1) regulates osteoclast function and bone mass

    OpenAIRE

    Menon, Prashanthi; Yin, Guoyong; Smolock, Elaine M.; Zuscik, Michael J.; Yan, Chen; Berk, Bradford C.

    2010-01-01

    G-protein coupled receptor (GPCR) kinase 2 interacting protein-1 (GIT1) is a scaffold protein expressed in various cell types including neurons, endothelial and vascular smooth muscle cells. The GIT1 knockout (KO) mouse has a pulmonary phenotype due to impaired endothelial function. Because GIT1 is tyrosine phosphorylated by Src kinase, we anticipated that GIT1 KO should have a bone phenotype similar to Src KO. Microcomputed tomography of the long bones revealed that GIT1 KO mice have a 2.3-f...

  17. Impaired spine formation and learning in GPCR kinase interacting protein-1 (GIT1) knockout mice

    OpenAIRE

    Menon, Prashanthi; Deane, Rashid; Sagare, Abhay; Lane, Steven M.; Zarcone, Troy J; O’Dell, Michael R.; Yan, Chen; Zlokovic, Berislav V.; Berk, Bradford C.

    2010-01-01

    The G-protein coupled receptor (GPCR)-kinase interacting proteins 1 and 2 (GIT1 and GIT2) are scaffold proteins with ADP-ribosylating factor GTPase activity. GIT1 and GIT2 control numerous cellular functions and are highly expressed in neurons, endothelial cells and vascular smooth muscle cells (VSMC). GIT1 promotes dendritic spine formation, growth and motility in cultured neurons, but its role in brain in vivo is unknown. By using global GIT1 knockout mice (GIT1 KO), we show that deletion o...

  18. Fragile X mental retardation protein interactions with the microtubule associated protein 1B RNA

    OpenAIRE

    Menon, Lakshmi; Mader, Samantha Ann; Mihailescu, Mihaela-Rita

    2008-01-01

    Fragile X mental retardation syndrome, the most common form of inherited mental retardation, is caused by the absence of the fragile X mental retardation protein (FMRP). FMRP has been shown to use its arginine–glycine–glycine (RGG) box to bind to a subset of RNA targets that form a G quadruplex structure. We performed a detailed analysis of the interactions between the FMRP RGG box and the microtubule associated protein 1B (MAP1B) mRNA, a relevant in vivo FMRP target. We show that MAP1B RNA f...

  19. 冠心病合并代谢综合征患者胰岛素抵抗与单细胞趋化蛋白-1的关系%The relationship between insulin resistance and monocyte chemoattractant protein-1 in patients with coronary heart disease and metabolic syndrome

    Institute of Scientific and Technical Information of China (English)

    乔平; 马业新; 郭小梅; 李新民

    2006-01-01

    目的 研究冠心病合并代谢综合征患者胰岛素抵抗与单核细胞趋化蛋白-1(MCP-1)表达的关系.方法 选择单纯代谢综合征患者37例(A组),单纯冠心病患者31例(B组),冠心病合并代谢综合征患者39例(C组)和正常对照组28例(D组).对所有受试者测量其身高、体重、腰围、臀围;测血脂、空腹血糖、胰岛素、MCP-1;计算体重指数、腰臀比、胰岛素抵抗指数并进行比较.结果 A、B、C 3组患者的胰岛素、胰岛素抵抗指数、MCP-1均高于D组,C组的胰岛素抵抗指数、MCP-1分别高于A、B两组.直线相关分析显示,胰岛素抵抗指数与体重指数、腰围、甘油三酯、空腹血糖、胰岛素和MCP-1呈正相关,与高密度脂蛋白呈负相关,差异有显著性意义;逐步回归分析显示,胰岛素抵抗指数与空腹血糖、胰岛素、甘油三酯、高密度脂蛋白、MCP-1、体重指数相关.结论 冠心病合并代谢综合征患者的胰岛素抵抗度和炎性因子MCP-1的表达异常升高,同时,胰岛素抵抗与MCP-1的异常表达相关.

  20. Real-time analysis of integrin-mediated chemotactic migration of T lymphocytes within 3-D extracellular matrix-like gels.

    Science.gov (United States)

    Franitza, S; Alon, R; Lider, O

    1999-05-27

    We have developed a novel 3-D gel reconstituted with major extracellular matrix (ECM) glycoproteins to follow the dynamics of migration of human T cells locomoting, in real-time, on gradients formed by representative chemoattractants: the C-C chemokine RANTES, and the pro-inflammatory cytokine IL-2. In the absence of chemoattractants, none of the T cells migrated directionally and the levels of random migration or cell polarization were low. However, major fractions of T cells placed in IL-2 and RANTES gradients in the gels polarized immediately after exposure to the chemoattractants. Shortly after polarization, 25% of the T cells migrated, in either a random or directional fashion, towards the sources of the chemoattractants; additional 5-10% of the cells remained polarized but stationary. The number of T cells migrating directionally towards RANTES or IL-2 peaked along with the formation of the chemotactic gradients. The directional migration of T cells was increased by a short pre-exposure to low doses of IL-2, which did not alter the level of expression of the beta1 integrins. The directional migration of T cells towards IL-2 and RANTES was mediated by IL-2R and pertussis toxin-sensitive receptors, respectively, and the directional, and to a lesser degree, the random locomotion of T cells induced by both chemoattractants required intact tyrosine kinase signaling and activities of the alpha4, alpha5, and, to a lesser degree, the alpha2 and alpha6 members the beta1 integrins. Our system enables the real-time tracking of individual locomoting lymphocytes and the analysis of their dynamic interactions with ECM components and cytokines. PMID:10365778

  1. The oxygen evolving enhancer protein 1 (OEE) of photosystem II in green algae exhibits thioredoxin activity.

    Science.gov (United States)

    Heide, Heinrich; Kalisz, Henryk M; Follmann, Hartmut

    2004-02-01

    A thioredoxin-like chloroplast protein of the fructosebisphosphatase-stimulating f-type, but with an unusually high molecular mass of 28 kDa has previously been identified and purified to homogeneity in a fractionation scheme for resolution of the acid- and heat-stable, regular-size (12kDa) thioredoxins of the unicellular green algae, Scenedesmus obliquus. An apparently analogous protein of 26 kDa was described in a cyanobacterium, Anabaena sp., but no such large thioredoxin species f exists in the thioredoxin profiles of higher plants. The structure of the 28 kDa protein, which had been envisaged to represent a precursor, or fusion product of the two more specialized, common chloroplast thioredoxins f and m has now been determined by amino acid sequencing. Although it exhibits virtually all the properties and enzyme-modulating activities of a thioredoxin proper this algal protein, surprisingly, does not belong to the thioredoxin family of small redox proteins but is identical with OEE (oxygen evolving enhancer) protein 1, an auxiliary component of the photosystem II manganese cluster. Extracts of Chlorella vulgaris and Chlamydomonas reinhardtii also contain heat-stable protein fractions of 23-26 kDa capable of specifically stimulating chloroplast fructosebisphosphatase in vitro. In contrast, OEE protein 1 from spinach is not able to modulate FbPase or NADP malate dehydrogenase from spinach chloroplasts. A dual function of the OEE protein in algal photosynthesis is envisaged. PMID:15022827

  2. Spatiotemporal patterns of the Huntingtin-interacting protein 1-related gene in the mouse head.

    Science.gov (United States)

    Masuda, Tomoyuki; Sakuma, Chie; Ueno, Takayuki; Yamada, Yuriko; Ohmomo, Hideki; Ueda, Shuichi; Yamagishi, Toshiyuki; Yaginuma, Hiroyuki

    2013-12-01

    Huntingtin-interacting protein 1-related (Hip1r) was originally identified due to its homology to Huntingtin-interacting protein 1, which contributes to the development of Huntington's disease (HD). We studied the expression of the mouse Hip1r (mHip1r) gene in the mouse head by in situ hybridization. In early embryogenesis at embryonic day (E) 13, mHip1r expression was especially prominent in the olfactory epithelium, cerebral cortex layer 1, cortical plate, and dentate gyrus. During later development from E15 to E17, strong expression of mHip1r transcripts continued to be observed in the olfactory epithelium, cortical plate, and dentate gyrus. Furthermore, not only the subplate and subventricular zone of the cortex, but also secretory glands, such as the nasal gland and the submandibular gland, were mHip1r-positive. Other positive tissues included the retinal ganglion cells, vomeronasal organ, trigeminal ganglion, and the developing molar tooth. In the adult mouse brain, similar expression patterns were observed in the cerebral cortex layers and other brain regions except the cerebellum. Additionally, by using an antibody against mHip1r, we confirmed these expression patterns at the protein level. Specific expression of mHip1r in the embryonic brain and secretory glands suggests a possible role for Hip1r in normal development and in the pathology of HD. PMID:24712472

  3. Epilepsy, Behavioral Abnormalities, and Physiological Comorbidities in Syntaxin-Binding Protein 1 (STXBP1 Mutant Zebrafish.

    Directory of Open Access Journals (Sweden)

    Brian P Grone

    Full Text Available Mutations in the synaptic machinery gene syntaxin-binding protein 1, STXBP1 (also known as MUNC18-1, are linked to childhood epilepsies and other neurodevelopmental disorders. Zebrafish STXBP1 homologs (stxbp1a and stxbp1b have highly conserved sequence and are prominently expressed in the larval zebrafish brain. To understand the functions of stxbp1a and stxbp1b, we generated loss-of-function mutations using CRISPR/Cas9 gene editing and studied brain electrical activity, behavior, development, heart physiology, metabolism, and survival in larval zebrafish. Homozygous stxbp1a mutants exhibited a profound lack of movement, low electrical brain activity, low heart rate, decreased glucose and mitochondrial metabolism, and early fatality compared to controls. On the other hand, homozygous stxbp1b mutants had spontaneous electrographic seizures, and reduced locomotor activity response to a movement-inducing "dark-flash" visual stimulus, despite showing normal metabolism, heart rate, survival, and baseline locomotor activity. Our findings in these newly generated mutant lines of zebrafish suggest that zebrafish recapitulate clinical phenotypes associated with human syntaxin-binding protein 1 mutations.

  4. Nuclear Multidrug-Resistance Related Protein 1 Contributes to Multidrug-Resistance of Mucoepidermoid Carcinoma Mainly via Regulating Multidrug-Resistance Protein 1: A Human Mucoepidermoid Carcinoma Cells Model and Spearman's Rank Correlation Analysis

    OpenAIRE

    Bolei Cai; Ye Miao; Yuan Liu; Xiaofang Xu; Sumin Guan; Junzheng Wu; Yanpu Liu

    2013-01-01

    BACKGROUND: Multidrug resistance-related protein 1 (MRP1/ABCC1) and multidrug resistance protein 1 (MDR1/P-glycoprotein/ABCB1) are both membrane-bound drug transporters. In contrast to MDR1, MRP1 also transports glutathione (GSH) and drugs conjugated to GSH. Due to its extraordinary transport properties, MRP1/ABCC1 contributes to several physiological functions and pathophysiological incidents. We previously found that nuclear translocation of MRP1 contributes to multidrug-resistance (MDR) of...

  5. Chronic alcohol-induced microRNA-155 contributes to neuroinflammation in a TLR4-dependent manner in mice.

    Directory of Open Access Journals (Sweden)

    Dora Lippai

    Full Text Available INTRODUCTION: Alcohol-induced neuroinflammation is mediated by pro-inflammatory cytokines and chemokines including tumor necrosis factor-α (TNFα, monocyte chemotactic protein-1 (MCP1 and interleukin-1-beta (IL-1β. Toll-like receptor-4 (TLR4 pathway induced nuclear factor-κB (NF-κB activation is involved in the pathogenesis of alcohol-induced neuroinflammation. Inflammation is a highly regulated process. Recent studies suggest that microRNAs (miRNAs play crucial role in fine tuning gene expression and miR-155 is a major regulator of inflammation in immune cells after TLR stimulation. AIM: To evaluate the role of miR-155 in the pathogenesis of alcohol-induced neuroinflammation. METHODS: Wild type (WT, miR-155- and TLR4-knockout (KO mice received 5% ethanol-containing or isocaloric control diet for 5 weeks. Microglia markers were measured by q-RTPCR; inflammasome activation was measured by enzyme activity; TNFα, MCP1, IL-1β mRNA and protein were measured by q-RTPCR and ELISA; phospho-p65 protein and NF-κB were measured by Western-blotting and EMSA; miRNAs were measured by q-PCR in the cerebellum. MiR-155 was measured in immortalized and primary mouse microglia after lipopolysaccharide and ethanol stimulation. RESULTS: Chronic ethanol feeding up-regulated miR-155 and miR-132 expression in mouse cerebellum. Deficiency in miR-155 protected mice from alcohol-induced increase in inflammatory cytokines; TNFα, MCP1 protein and TNFα, MCP1, pro-IL-1β and pro-caspase-1 mRNA levels were reduced in miR-155 KO alcohol-fed mice. NF-κB was activated in WT but not in miR-155 KO alcohol-fed mice. However increases in cerebellar caspase-1 activity and IL-1β levels were similar in alcohol-fed miR-155-KO and WT mice. Alcohol-fed TLR4-KO mice were protected from the induction of miR-155. NF-κB activation measured by phosphorylation of p65 and neuroinflammation were reduced in alcohol-fed TLR4-KO compared to control mice. TLR4 stimulation with

  6. Platelet and monocyte activity markers and mediators of inflammation in Takotsubo cardiomyopathy.

    Science.gov (United States)

    Pirzer, Rainer; Elmas, Elif; Haghi, Dariusch; Lippert, Christiane; Kralev, Stefan; Lang, Siegfried; Borggrefe, Martin; Kälsch, Thorsten

    2012-03-01

    Patients with Takotsubo cardiomyopathy (TC) often present with symptoms similar to those of myocardial infarction (MI). We analyzed blood concentrations of mediators of inflammation and platelet- and monocyte-activity markers in patients with TC and MI for significant differences. Clinical data of patients with TC (n = 16) and acute MI (n = 16) were obtained. Serial blood samples were taken at the time of hospital admission (t(0)), after 2-4 days (t(1)) and after 4-7 weeks (t(2)), respectively. Plasma concentrations of interleukin (IL)-6, IL-7, soluble CD40 ligand (sCD40L), and monocyte chemotactic protein 1 (MCP-1) were determined with an ELISA. Tissue factor binding on monocytes, platelet-activation marker CD62P, platelet CD40-ligand (CD40L), and platelet-monocyte aggregates were measured using flow cytometry. Expression of CD62P on platelets and IL-6 plasma levels were significantly lower in patients with TC compared to MI at the time of hospital admission. IL-7 plasma levels were significantly elevated in patients with TC compared to patients with MI at 2-4 days after hospital admission. No significant differences were observed concerning sCD40L and MCP-1 plasma levels, tissue factor binding on monocytes, CD40L expression on platelets, and platelet-monocyte aggregates at any point in time. Our results indicate that inflammatory mediators and platelet-activity markers contribute to the differences in the pathogenesis of MI and TC. PMID:21416113

  7. L-selectin and P-selectin are novel biomarkers of cervicovaginal inflammation for preclinical mucosal safety assessment of anti-HIV-1 microbicide.

    Science.gov (United States)

    Zhong, Maohua; He, Benxia; Yang, Jingyi; Bao, Rong; Zhang, Yan; Zhou, Dihan; Chen, Yaoqing; Li, Liangzhu; Han, Chen; Yang, Yi; Sun, Ying; Cao, Yuan; Li, Yaoming; Shi, Wei; Jiang, Shibo; Zhang, Xiaoyan; Yan, Huimin

    2012-06-01

    A major obstacle thwarting preclinical development of microbicides is the lack of a validated biomarker of cervicovaginal inflammation. Therefore, the present study aims to identify novel noninvasive soluble markers in a murine model for assessment of microbicide mucosal safety. By performing cytokine antibody array analysis, we identified two adhesion molecules, L-selectin and P-selectin, which significantly increased when mucosal inflammation was triggered by nonoxynol-9 (N9), an anti-HIV-1 microbicide candidate that failed clinical trials, in a refined murine model of agent-induced cervicovaginal inflammation. We found that patterns of detection of L-selectin and P-selectin were obviously different from those of the two previously defined biomarkers of cervicovaginal inflammation, monocyte chemotactic protein 1 (MCP-1) and interleukin 6 (IL-6). The levels of these two soluble selectins correlated better than those of MCP-1 and IL-6 with the duration and severity of mucosal inflammation triggered by N9 and two approved proinflammatory compounds, benzalkonium chloride (BZK) and sodium dodecyl sulfate (SDS), but not by two nonproinflammatory compounds, carboxymethyl celluose (CMC; microbicide excipients) and tenofovir (TFV; microbicide candidate). These data indicated that L-selectin and P-selectin can serve as additional novel cervicovaginal inflammation biomarkers for preclinical mucosal safety evaluation of candidate microbicides for the prevention of infection with HIV and other sexually transmitted pathogens. PMID:22391529

  8. Xanthones from Securidaca inappendiculata exert significant therapeutic efficacy on adjuvant-induced arthritis in mice.

    Science.gov (United States)

    Zuo, Jian; Xia, Yan; Li, Xiang; Chen, Jian-Wei

    2014-06-01

    The study was designed to investigate effects of the xanthones from Securidaca inappendiculata on adjuvant-induced arthritis (AA) mice in vivo. Arthritis severity was evaluated by arthritic score, body weight loss, paw circumference, histological changes and hyperplasia of lymphatic tissues. Plasma samples were collected for estimation of interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-α), monocyte chemotactic protein 1 (MCP-1) and vascular endothelial growth factor (VEGF) using enzyme-linked immunosorbent assay method. The levels of glutathione (GSH), malondialdehyde (MDA), N-acetyl glucosaminidase (NAG) and sialic acid (SA) in liver were assessed by colorimetric method. Xanthones significantly ameliorated the severity of AA indicated by the physical parameters changes, and reverted the abnormal changes of MDA, GSH, NAG and SA in liver. Levels of IL-1, TNF-α, MCP-1 and VEGF reduced dramatically meanwhile. The effects of xanthones on AA were the outcome of the multitargets activities, and probably associated with NF-κB signaling pathway. PMID:24419745

  9. Dietary lactoferrin alleviates age-related lacrimal gland dysfunction in mice.

    Directory of Open Access Journals (Sweden)

    Motoko Kawashima

    Full Text Available BACKGROUND: Decrease in lacrimal gland secretory function is related to age-induced dry eye disease. Lactoferrin, the main glycoprotein component of tears, has multiple functions, including anti-inflammatory effects and the promotion of cell growth. We investigated how oral administration of lactoferrin affects age-related lacrimal dysfunction. METHODS AND FINDINGS: Twelve-month-old male C57BL/6Cr Slc mice were randomly divided into a control fed group and an oral lactoferrin treatment group. Tear function was measured at a 6-month time-point. After euthanasia, the lacrimal glands were subjected to histological examination with 8-hydroxy-2'-deoxyguanosine (8-OHdG antibodies, and serum concentrations of 8-OHdG and hexanoyl-lysine adduct (HEL were evaluated. Additionally, monocyte chemotactic protein-1(MCP-1 and tumor necrosis factor-α (TNF-α gene expression levels were determined by real-time PCR. The volume of tear secretion was significantly larger in the treated group than in the control. Lactoferrin administration reduced inflammatory cell infiltration and the MCP-1 and TNF-α expression levels. Serum concentrations of 8-OHdG and HEL in the lactoferrin group were lower than those in the control group and were associated with attenuated 8-OHdG immunostaining of the lacrimal glands. CONCLUSION: Oral lactoferrin administration preserves lacrimal gland function in aged mice by attenuating oxidative damage and suppressing subsequent gland inflammation.

  10. Synergistic Cytotoxic Effects of Ganoderma lucidum and Bacillus Calmette Guérin on Premalignant Urothelial HUC-PC Cells and Its Regulation on Proinflammatory Cytokine Secretion

    Directory of Open Access Journals (Sweden)

    John Wai-man Yuen

    2012-01-01

    Full Text Available Bacillus Calmette-Guérin (BCG is conventionally used as an adjuvant immunotherapy to reduce the recurrence of bladder cancer. To address the issues of efficacy and safety, an ethanol extract of Ganoderma lucidum (GLe was evaluated for its interaction with BCG. In a model of premalignant human uroepithelial cells (HUC-PC, GLe exerted immediate cytotoxic effects while BCG showed a delayed response, given that both were immunological active in inducing the secretion of interleukin (IL-6, IL-8, and monocyte chemotactic protein-1 (MCP-1. Synergistic cytotoxic effects were observed when cells were either coincubated with both drugs or firstly preincubated with GLe. Synergism between GLe and BCG was demonstrated to achieve a complete cytostasis in 24 hours, and such effects were progressed in the subsequent 5 days. However, the pretreatment of GLe resulted in suppression of IL-6, IL-8, and MCP-1 secretions without affecting the cytotoxicity. Given that numerous proinflammatory cytokines are associated with the high side effects toll of BCG, results herein suggested the potential implications of GL to supplement the BCG immunotherapy in bladder cancer, for better efficacy and reducing side effects.

  11. Toll-like receptor 11-initiated innate immune response in male mouse germ cells.

    Science.gov (United States)

    Chen, Qiaoyuan; Zhu, Weiwei; Liu, Zhenghui; Yan, Keqin; Zhao, Shutao; Han, Daishu

    2014-02-01

    Toxoplasma gondii and uropathogenic Escherichia coli (UPEC) may infect the testis and impair testicular function. Mechanisms underlying testicular innate immune response to these two pathogens remain to be clarified. The present study examined the function of TLR11, which can be recognized by T. gondii-derived profilin and UPEC, in initiating innate immune response in male mouse germ cells. TLR11 is predominantly expressed in spermatids. Profilin and UPEC induced the expressions of different inflammatory cytokine profiles in the germ cells. In particular, profilin induced the expressions of macrophage chemotactic protein 1 (MCP1), interleukin 12 (IL12), and interferon gamma (IFNG) through nuclear factor KB (NFKB) activation. UPEC induced the expressions of MCP1, IL12, and IFNG, as well as tumor necrosis factor alpha (TNFA), IL6, and IFNB, through the activation of NFKB, IFN regulatory factor 3, and mitogen-activated protein kinases. Evidence showed that profilin induced the innate response in male germ cells through TLR11 signaling, and UPEC triggered the response through TLR11 and other TLR-signaling pathways. We also provided evidence that local injection of profilin or UPEC induces the innate immune response in the germ cells. Data describe TLR11-mediated innate immune function of male germ cells in response to T. gondii profilin and UPEC stimulations. This system may play a role in testicular defense against T. gondii and UPEC infections in mice.

  12. Resveratrol increases nephrin and podocin expression and alleviates renal damage in rats fed a high-fat diet.

    Science.gov (United States)

    Pan, Qing-Rong; Ren, Yan-Long; Zhu, Jia-Jia; Hu, Yan-Jin; Zheng, Jin-Su; Fan, Hui; Xu, Yuan; Wang, Guang; Liu, Wen-Xian

    2014-07-14

    Resveratrol is well known for its anti-inflammation and anti-oxidant properties, and has been shown to be effective in alleviating the development of obesity. The purpose of this investigation was to analyze the effect of resveratrol on renal damage in obese rats induced by a high-fat diet (HFD) and its possible mechanisms. Male Sprague-Dawley rats were divided into three groups: control, HFD, and HFD plus resveratrol (treated with 100 mg/kg/day resveratrol). Body weight, serum and urine metabolic parameters, and kidney histology were measured. Meanwhile, the activities of nuclear factor-κB (NF-κB) and superoxide dismutase (SOD), the content of malondialdehyde (MDA), and the protein levels of tumor necrosis factor (TNF-α), monocyte chemotactic protein-1 (MCP-1), nephrin and podocin in kidney were detected. Our work showed that resveratrol alleviated dyslipidemia and renal damage induced by HFD, decreased MDA level and increased SOD activity. Furthermore, the elevated NF-κB activity, increased TNF-α and MCP-1 levels, and reduced expressions of nephrin and podocin induced by HFD were significantly reversed by resveratrol. These results suggest resveratrol could ameliorate renal injury in rats fed a HFD, and the mechanisms are associated with suppressing oxidative stress and NF-κB signaling pathway that in turn up-regulate nephrin and podocin protein expression.

  13. Resveratrol Increases Nephrin and Podocin Expression and Alleviates Renal Damage in Rats Fed a High-Fat Diet

    Directory of Open Access Journals (Sweden)

    Qing-Rong Pan

    2014-07-01

    Full Text Available Resveratrol is well known for its anti-inflammation and anti-oxidant properties, and has been shown to be effective in alleviating the development of obesity. The purpose of this investigation was to analyze the effect of resveratrol on renal damage in obese rats induced by a high-fat diet (HFD and its possible mechanisms. Male Sprague-Dawley rats were divided into three groups: control, HFD, and HFD plus resveratrol (treated with 100 mg/kg/day resveratrol. Body weight, serum and urine metabolic parameters, and kidney histology were measured. Meanwhile, the activities of nuclear factor-κB (NF-κB and superoxide dismutase (SOD, the content of malondialdehyde (MDA, and the protein levels of tumor necrosis factor (TNF-α, monocyte chemotactic protein-1 (MCP-1, nephrin and podocin in kidney were detected. Our work showed that resveratrol alleviated dyslipidemia and renal damage induced by HFD, decreased MDA level and increased SOD activity. Furthermore, the elevated NF-κB activity, increased TNF-α and MCP-1 levels, and reduced expressions of nephrin and podocin induced by HFD were significantly reversed by resveratrol. These results suggest resveratrol could ameliorate renal injury in rats fed a HFD, and the mechanisms are associated with suppressing oxidative stress and NF-κB signaling pathway that in turn up-regulate nephrin and podocin protein expression.

  14. Consumption of a high-fat meal containing cheese compared with a vegan alternative lowers postprandial C-reactive protein in overweight and obese individuals with metabolic abnormalities: a randomised controlled cross-over study.

    Science.gov (United States)

    Demmer, Elieke; Van Loan, Marta D; Rivera, Nancy; Rogers, Tara S; Gertz, Erik R; German, J Bruce; Zivkovic, Angela M; Smilowitz, Jennifer T

    2016-01-01

    Dietary recommendations suggest decreased consumption of SFA to minimise CVD risk; however, not all foods rich in SFA are equivalent. To evaluate the effects of SFA in a dairy food matrix, as Cheddar cheese, v. SFA from a vegan-alternative test meal on postprandial inflammatory markers, a randomised controlled cross-over trial was conducted in twenty overweight or obese adults with metabolic abnormalities. Individuals consumed two isoenergetic high-fat mixed meals separated by a 1- to 2-week washout period. Serum was collected at baseline, and at 1, 3 and 6 h postprandially and analysed for inflammatory markers (IL-6, IL-8, IL-10, IL-17, IL-18, TNFα, monocyte chemotactic protein-1 (MCP-1)), acute-phase proteins C-reactive protein (CRP) and serum amyloid-A (SAA), cellular adhesion molecules and blood lipids, glucose and insulin. Following both high-fat test meals, postprandial TAG concentrations rose steadily (P vegan-alternative test meal. A treatment effect was not observed for any other inflammatory markers; however, for both test meals, multiple markers significantly changed from baseline over the 6 h postprandial period (IL-6, IL-8, IL-18, TNFα, MCP-1, SAA). Saturated fat in the form of a cheese matrix reduced the iAUC for CRP compared with a vegan-alternative test meal during the postprandial 6 h period. The study is registered at clinicaltrials.gov under NCT01803633.

  15. Ubiquitin Fusion Degradation Protein 1 as a Blood Marker for The Early Diagnosis of Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Laure Allard

    2007-01-01

    Full Text Available Background: Efficacy of thrombolysis in acute ischemic stroke is strongly related to physician’s ability to make an accurate diagnosis and to intervene within 3–6 h after event onset. In this context, the discovery and validation of very early blood markers have recently become an urgent, yet unmet, goal of stroke research. Ubiquitin fusion degradation protein 1 is increased in human postmortem CSF, a model of global brain insult, suggesting that its measurement in blood may prove useful as a biomarker of stroke.Methods: Enzyme-linked immunosorbent assay (ELISA was used to measure UFD1 in plasma and sera in three independent cohorts, European (Swiss and Spanish and North-American retrospective analysis encompassing a total of 123 consecutive stroke and 90 control subjects.Results: Highly significant increase of ubiquitin fusion degradation protein 1 (UFD1 was found in Swiss stroke patients with 71% sensitivity (95% CI, 52–85.8%, and 90% specificity (95% CI, 74.2–98% (N = 31, p < 0.0001. Significantly elevated concentration of this marker was then validated in Spanish (N = 39, p < 0.0001, 95% sensitivity (95% CI, 82.7–99.4%, 76% specificity (95% CI, 56.5–89.7% and North-American stroke patients (N = 53, 62% sensitivity (95% CI, 47.9–75.2%, 90% specificity (95% CI, 73.5–97.9%, p < 0.0001. Its concentration was increased within 3 h of stroke onset, on both the Swiss (p < 0.0001 and Spanish (p = 0.0004 cohorts.Conclusions: UFD1 emerges as a reliable plasma biomarker for the early diagnosis of stroke, and in the future, might be used in conjunction with clinical assessments, neuroimaging and other blood markers.Abbreviations: AUC: area under curve; BBB: blood–brain barrier; CO: cut-off; CSF: cerebrospinal fluid; CT: computerized tomography; H-FABP: heart-fatty acid binding protein; MMP9: matrix metalloproteinase 9; MRI: magnetic resonance imaging; NDKA: nucleotide diphosphate kinase A; OR: odds ratio; RFU: relative fluorescence

  16. Dermatan sulfate reduces monocyte chemoattractant protein 1 and TGF-β production, as well as macrophage recruitment and myofibroblast accumulation in mice with unilateral ureteral obstruction

    Directory of Open Access Journals (Sweden)

    C.L.R. Belmiro

    2011-07-01

    Full Text Available Selectins play an essential role in most inflammatory reactions, mediating the initial leukocyte-rolling event on activated endothelium. Heparin and dermatan sulfate (DS bind and block P- and L-selectin function in vitro. Recently, we reported that subcutaneous administration of DS inhibits colon inflammation in rats by reducing macrophage and T-cell recruitment and macrophage activation. In the present study, we examined the effect of porcine intestinal mucosa DS on renal inflammation and fibrosis in mice after unilateral ureteral obstruction (UUO. Twenty-four adult male Swiss mice weighing 20-25 g were divided into 4 groups: group C (N = 6 was not subjected to any surgical manipulation; group SH (N = 6 was subjected to surgical manipulation but without ureter ligation; group UUO (N = 6 was subjected to unilateral ureteral obstruction and received no treatment; group UUO plus DS (N = 6 was subjected to UUO and received DS (4 mg/kg subcutaneously daily for 14 days. An immunoblot study was also performed for TGF-β. Collagen (stained area ~3700 µm², MCP-1 (stained area ~1700 µm², TGF-β (stained area ~13% of total area, macrophage (number of cells ~40, and myofibroblast (stained area ~1900 µm² levels were significantly (P < 0.05 higher in the UUO group compared to control. DS treatment significantly (P < 0.05 reduced the content of collagen (stained area ~700 µm², MCP-1 (stained area ~160 µm² and TGF-β (stained area ~5% of total area, in addition to myofibroblast (stained area ~190 µm² and macrophage (number of cells ~32 accumulation in the obstructed kidney. Overall, these results indicate that DS attenuates kidney inflammation by reducing macrophage recruitment, myofibroblast population and fibrosis in mice submitted to UUO.

  17. Involvement of fractalkine and macrophage inflammatory protein-1 alpha in moderate-severe depression

    Directory of Open Access Journals (Sweden)

    Rosaria Alba Merendino

    2004-01-01

    Full Text Available MODERATE-severe depression (MSD is linked to overexpression of proinflammatory cytokines and chemokines. Fractalkine (FKN and macrophage inflammatory protein-1 alpha (MIP-1α are, respectively, members of CX3C and C-C chemokines, and both are involved in recruiting and activating mononuclear phagocytes in the central nervous system. We analysed the presence of FKN and MIP-1α in sera of untreated MSD patients and healthy donors. High FKN levels were observed in all MSD patients as compared with values only detectable in 26% of healthy donors. MIP-1α was measurable in 20% of patients, while no healthy donors showed detectable chemokine levels. In conclusion, we describe a previously unknown involvement of FKN in the pathogenesis of MSD, suggesting that FKN may represent a target for a specific immune therapy of this disease.

  18. Expression of the lysosomal-associated membrane protein-1 (LAMP-1) in astrocytomas

    DEFF Research Database (Denmark)

    Jensen, Stine S; Aaberg-Jessen, Charlotte; Christensen, Karina G;

    2013-01-01

    Targeting of lysosomes is a novel therapeutic anti-cancer strategy for killing the otherwise apoptosis-resistant cancer cells. Such strategies are urgently needed for treatment of brain tumors, especially the glioblastoma, which is the most frequent and most malignant type. The aim of the present...... study was to investigate the presence of lysosomes in astrocytic brain tumors focussing also on the therapy resistant tumor stem cells. Expression of the lysosomal marker LAMP-1 (lysosomal-associated membrane protein-1) was investigated by immunohistochemistry in 112 formalin fixed paraffin embedded...... individual tumor grades. LAMP-1/GFAP showed pronounced co-expression and LAMP-1/CD133 was co-expressed as well suggesting that tumor cells including the proposed tumor stem cells contain lysosomes. The results suggest that high amounts of lysosomes are present in glioblastomas and in the proposed tumor stem...

  19. Dynamin-Related Protein 1 Translocates from the Cytosol to Mitochondria during UV-Induced Apoptosis

    International Nuclear Information System (INIS)

    Mitochondria are dynamic structures that frequently divide and fuse with one another to form interconnecting network. This network disintegrates into punctiform organelles during apoptosis. However, the mechanisms involved in these processes are still not well characterized. In this study, we investigate the role of dynamin-related protein 1 (Drp1), a large GTPase that mediates outer mitochondrial membrane fission, in mitochondrial dynamics in response to UV irradiation in human lung adenocarcinoma cells (ASTC-α-1) and HeLa cells. Using time-lapse fluorescent imaging, we find that Drp1 primarily distributes in cytosol under physiological conditions. After UV treatment, Drp1 translocates from cytosol to mitochondria, indicating the enhancement of Drp1 mitochondrial accumulation. Our results suggest that Drp1 is involved in the regulation of transition from an interconnecting network to a punctiform mitochondrial phenotype during UV-induced apoptosis.

  20. Plasmodium falciparum Erythrocyte Membrane Protein 1 Diversity in Seven Genomes – Divide and Conquer

    DEFF Research Database (Denmark)

    Rask, Thomas Salhøj; Hansen, Daniel Aaen; Theander, Thor G.;

    2010-01-01

    The var gene encoded hyper-variable Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family mediates cytoadhesion of infected erythrocytes to human endothelium. Antibodies blocking cytoadhesion are important mediators of malaria immunity acquired by endemic populations. The development...... of a PfEMP1 based vaccine mimicking natural acquired immunity depends on a thorough understanding of the evolved PfEMP1 diversity, balancing antigenic variation against conserved receptor binding affinities. This study redefines and reclassifies the domains of PfEMP1 from seven genomes. Analysis...... of domains in 399 different PfEMP1 sequences allowed identification of several novel domain classes, and a high degree of PfEMP1 domain compositional order, including conserved domain cassettes not always associated with the established group A–E division of PfEMP1. A novel iterative homology block (HB...

  1. Analyzing Plasmodium falciparum erythrocyte membrane protein 1 gene expression by a next generation sequencing based method

    DEFF Research Database (Denmark)

    Jespersen, Jakob S.; Petersen, Bent; Seguin-Orlando, Andaine;

    2013-01-01

    Plasmodium falciparum is responsible for most cases of severe malaria and causes >1 million deaths every year. The particular virulence of this Plasmodium species is highly associated with the expression of certain members of the Plasmodium falciparum erythrocyte membrane protein 1(PfEMP1) family......, encoded by ~60 highly variable 'var' genes per haploid genome. PfEMP1 is exported to the surface of infected erythrocytes and is thought to be fundamental to immune evasion by adhesion to host and parasite factors. The highly variable nature has constituted a roadblock in var expression studies aimed...... at identifying PfEMP1 features associated with high virulence. Here we present the first effective method for sequence analysis of var genes expressed in field samples: a sequential PCR and next generation sequencing based technique applied on expressed var sequence tags and subsequently on long range PCR...

  2. Human Cementum Protein 1 induces expression of bone and cementum proteins by human gingival fibroblasts

    International Nuclear Information System (INIS)

    We recently presented evidence showing that a human cementoblastoma-derived protein, named Cementum Protein 1 (CEMP1) may play a role as a local regulator of cementoblast differentiation and cementum-matrix mineralization. This protein was shown to be expressed by cementoblasts and progenitor cells localized in the periodontal ligament. In this study we demonstrate that transfection of CEMP1 into human gingival fibroblasts (HGF) induces mineralization and expression of bone and cementum-matrix proteins. The transfected HGF cells had higher alkaline phosphatase activity and proliferation rate and they expressed genes for alkaline phosphatase, bone sialoprotein, osteocalcin, osteopontin, the transcription factor Runx2/Cbfa1, and cementum attachment protein (CAP). They also produced biological-type hydroxyapatite. These findings indicate that the CEMP1 might participate in differentiation and mineralization of nonosteogenic cells, and that it might have a potential function in cementum and bone formation

  3. In Vivo Detection of Vascular Adhesion Protein-1 in Experimental Inflammation

    Science.gov (United States)

    Jaakkola, Kimmo; Nikula, Tuomo; Holopainen, Riikka; Vähäsilta, Tommi; Matikainen, Marja-Terttu; Laukkanen, Marja-Leena; Huupponen, Risto; Halkola, Lauri; Nieminen, Lauri; Hiltunen, Jukka; Parviainen, Sakari; Clark, Michael R.; Knuuti, Juhani; Savunen, Timo; Kääpä, Pekka; Voipio-Pulkki, Liisa Maria; Jalkanen, Sirpa

    2000-01-01

    Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible endothelial glycoprotein which mediates leukocyte-endothelial cell interactions. To study the pathogenetic significance of VAP-1 in inflammatory disorders, an in vivo immunodetection method was used to detect the regulation of luminally expressed VAP-1 in experimental skin and joint inflammation in the pig and dog. Moreover, VAP-1 was studied as a potential target to localize inflammation by radioimmunoscintigraphy. Up-regulation of VAP-1 in experimental dermatitis and arthritis could be visualized by specifically targeted immunoscintigraphy. Moreover, the translocation of VAP-1 to the functional position on the endothelial surface was only seen in inflamed tissues. These results suggest that VAP-1 is both an optimal candidate for anti-adhesive therapy and a potential target molecule for imaging inflammation. PMID:10934150

  4. AMYLOID-β PEPTIDE BINDS TO MICROTUBULE-ASSOCIATED PROTEIN 1B (MAP1B)

    Science.gov (United States)

    Gevorkian, Goar; Gonzalez-Noriega, Alfonso; Acero, Gonzalo; Ordoñez, Jorge; Michalak, Colette; Munguia, Maria Elena; Govezensky, Tzipe; Cribbs, David H.; Manoutcharian, Karen

    2008-01-01

    Extracellular and intraneuronal formation of amyloid-beta aggregates have been demonstrated to be involved in the pathogenesis of Alzheimer’s disease. However, the precise mechanism of amyloid-beta neurotoxicity is not completely understood. Previous studies suggest that binding of amyloid-beta to a number of targets have deleterious effects on cellular functions. In the present study we have shown for the first time that amyloid-beta 1-42 bound to a peptide comprising the microtubule binding domain of the heavy chain of microtubule-associated protein 1B by the screening of a human brain cDNA library expressed on M13 phage. This interaction may explain, in part, the loss of neuronal cytoskeletal integrity, impairment of microtubule-dependent transport and synaptic dysfunction observed previously in Alzheimer’s disease. PMID:18079022

  5. Uncoupling protein 1 (UCP1 of brown adipocyte, the only uncoupler: historical perspective

    Directory of Open Access Journals (Sweden)

    Daniel eRicquier

    2011-12-01

    Full Text Available Uncoupling protein 1 - UCP1, is a unique mitochondrial membranous protein devoted to adaptive thermogenesis, a specialized function operated by the highly specialized oxidative brown adipocytes. Whereas the family of mitochondrial metabolite carriers comprises ~40 members including UCP1, the UCP1 is specifically identified by its ability to translocate protons through the inner membrane of brown adipocyte mitochondria. Doing that, UCP1 uncouples respiration from ATP synthesis and therefore provokes energy dissipation of oxidative energy as heat while, in parallel it markedly stimulates respiration and activates fatty acid oxidation. UCP1 homologues were identified but they are biochemically and physiologically different from UCP1. Thirty five years after its identification, UCP1 still appears as a fascinating component, and the recent renewal of the interest in human brown adipose tissue makes UCP1 as a potential target for strategies of treatment of metabolic disorders.

  6. Multiple Plasmodium falciparum Merozoite Surface Protein 1 Complexes Mediate Merozoite Binding to Human Erythrocytes.

    Science.gov (United States)

    Lin, Clara S; Uboldi, Alessandro D; Epp, Christian; Bujard, Hermann; Tsuboi, Takafumi; Czabotar, Peter E; Cowman, Alan F

    2016-04-01

    Successful invasion of human erythrocytes byPlasmodium falciparummerozoites is required for infection of the host and parasite survival. The early stages of invasion are mediated via merozoite surface proteins that interact with human erythrocytes. The nature of these interactions are currently not well understood, but it is known that merozoite surface protein 1 (MSP1) is critical for successful erythrocyte invasion. Here we show that the peripheral merozoite surface proteins MSP3, MSP6, MSPDBL1, MSPDBL2, and MSP7 bind directly to MSP1, but independently of each other, to form multiple forms of the MSP1 complex on the parasite surface. These complexes have overlapping functions that interact directly with human erythrocytes. We also show that targeting the p83 fragment of MSP1 using inhibitory antibodies inhibits all forms of MSP1 complexes and disrupts parasite growthin vitro.

  7. Serum concentration and interaction properties of MBL/ficolin associated protein-1

    DEFF Research Database (Denmark)

    Skjoedt, Mikkel-Ole; Hummelshoj, Tina; Palarasah, Yaseelan;

    2011-01-01

    Recently, a novel protein named MBL/ficolin associated protein-1 (MAP-1) derived from the MASP1 gene through differential splicing was identified. In the present study, we established biochemical characteristics, determined the serum level and assessed the interactions between the lectin complement...... pathway (LCP) recognition molecules and MAP-1. We expressed recombinant MAP-1 in CHO DG44 cells, developed a quantitative ELISA assay based on a MAP-1 specific monoclonal capture antibody and measured the serum levels in 100 Danish blood donors. In addition we assessed the association properties between...... without the signal peptide. We found that serum MAP-1 was very stable when subjected to repeated freeze and thaw cycles. The mean serum concentration of MAP-1 was found to be 240ng/ml (range: 115-466ng/ml). MAP-1 was predominantly found in complex with Ficolin-3 and to a lesser degree with Ficolin-2...

  8. Molecular modeling of the human multidrug resistance protein 1 (MRP1/ABCC1)

    International Nuclear Information System (INIS)

    Multidrug resistance protein 1 (MRP1/ABCC1) is a 190 kDa member of the ATP-binding cassette (ABC) superfamily of transmembrane transporters that is clinically relevant for its ability to confer multidrug resistance by actively effluxing anticancer drugs. Knowledge of the atomic structure of MRP1 is needed to elucidate its transport mechanism, but only low resolution structural data are currently available. Consequently, comparative modeling has been used to generate models of human MRP1 based on the crystal structure of the ABC transporter Sav1866 from Staphylococcus aureus. In these Sav1866-based models, the arrangement of transmembrane helices differs strikingly from earlier models of MRP1 based on the structure of the bacterial lipid transporter MsbA, both with respect to packing of the twelve helices and their interactions with the nucleotide binding domains. The functional importance of Tyr324 in transmembrane helix 6 predicted to project into the substrate translocation pathway was investigated

  9. Anti-Inflammatory Effect of the Blueberry Anthocyanins Malvidin-3-Glucoside and Malvidin-3-Galactoside in Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Wu-Yang Huang

    2014-08-01

    Full Text Available Blueberry fruits have a wide range of health benefits because of their abundant anthocyanins, which are natural antioxidants. The purpose of this study was to investigate the inhibitory effect of blueberry’s two main anthocyanins (malvidin-3-glucoside and malvidin-3-galactoside on inflammatory response in endothelial cells. These two malvidin glycosides could inhibit tumor necrosis factor-alpha (TNF-α induced increases of monocyte chemotactic protein-1 (MCP-1, intercellular adhesion molecule-1 (ICAM-1, and vascular cell adhesion molecule-1 (VCAM-1 production both in the protein and mRNA levels in a concentration-dependent manner. Mv-3-glc at the concentration of 1 μM could inhibit 35.9% increased MCP-1, 54.4% ICAM-1, and 44.7% VCAM-1 protein in supernatant, as well as 9.88% MCP-1 and 48.6% ICAM-1 mRNA expression (p < 0.05. In addition, they could decrease IκBα degradation (Mv-3-glc, Mv-3-gal, and their mixture at the concentration of 50 μM had the inhibition rate of 84.8%, 75.3%, and 43.2%, respectively, p < 0.01 and block the nuclear translocation of p65, which suggested their anti-inflammation mechanism was mediated by the nuclear factor-kappa B (NF-κB pathway. In general malvidin-3-glucoside had better anti-inflammatory effect than malvidin-3-galactoside. These results indicated that blueberry is good resource of anti-inflammatory anthocyanins, which can be promising molecules for the development of nutraceuticals to prevent chronic inflammation in many diseases.

  10. Proliferative and inflammatory factors in the vitreous of patients with proliferative diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    V V Chernykh

    2015-01-01

    Full Text Available Purpose: The purpose was to measure the concentrations of various cytokines and growth factors (including vascular endothelial growth factor [VEGF] and pigment epithelium-derived factor [PEDF] in the vitreous of patients with proliferative diabetic retinopathy (PDR and to investigate interaction between inflammatory and proliferative factors in the genesis of PDR. Materials and Methods : Vitreous samples from 32 eyes with PDR and 25 eyes without diabetes mellitus and signs of DR (control were collected. Vitreous concentrations of VEGF, PEDF, monocyte chemotactic protein-1 (MCP-1, interleukin-4 (IL-4, IL-6, IL-8, IL-10, IL-17A, and secretory immunoglobulin A (sIgA were simultaneously measured using enzyme-linked immunoassay. Results : Vitreous levels of VEGF, PEDF, IL-17A, IL-6, IL-8, IL-4, and sIgA were significantly (Π < 0.05 higher in eyes with PDR compared to control. The concentration of VEGF was more than 17-times higher than in control, and the concentration of PEDF was not changed oppositely and was also higher (1.45-times compared to control, that may indicate disturbances of compensatory mechanisms in angiogenesis regulation in PDR. Significant (Π < 0.05 positive correlations were observed between vitreous concentrations of VEGF and IL-17ΐ (r = 0.45, VEGF and IL-8 (r = 0.48, VEGF and IL-4 (r = 0.51, PEDF and IL-17ΐ (r = 0.48, PEDF and IL-8 (r = 0.59, MCP-1 and PEDF (r = 0.72, MCP-1 and IL-8 (r0 = 0.45, IL-4 and IL-17ΐ (r = 0.65, IL-4 and IL-8 (r = 0.71, IL-8 and IL-17ΐ (r = 0.59. Conclusions: Significantly raised levels of inflammatory and proliferative factors and numerous positive correlations between them may demonstrate a significant role of activation of vascular proliferation and local inflammation in the pathogenesis of PDR.

  11. Serumcytokinelevelsinchronichepatitis Bpatientsreceivingpeginterferon alpha-2atherapy

    Institute of Scientific and Technical Information of China (English)

    Yongjung Park; Jun Yong Park; Kwang-Hyub Han; Hyon-Suk Kim

    2012-01-01

    BACKGROUND: The relationship between cytokines and responses to peginterferonα-2a treatment in chronic hepatitis B patients has not yet been fully elucidated. We analyzed the serum levels of interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, vascular endothelial growth factor, interferon-γ, tumor necrosis factor-α, monocyte chemotactic protein-1 (MCP1) and epidermal growth factor during the treatment with peginterferonα-2a. METHODS: Ninety-three serum samples from 20 chronic hepatitis B patients were collected before, during and after 48 weeks of peginterferon therapy and were assayed for 12 cytokines. The patients were categorized as either virologic responders (VRs) or non-responders (NRs) according to their HBV DNA levels taken at 6th month during treatment. The Evidence Investigator (Randox, Antrim, UK), a protein chip analyzer, was used to quantify cytokines. RESULTS: Among the 12 cytokines, the levels of MCP1 were increased and the levels of IL-4 were decreased during the treatment in VRs. However these cytokines were not signiifcantly changed in NRs in the treatment phases. Area under the receiver operating characteristic curve (AUROC) value of HBV DNA measured before the treatment was 0.81 in predicting VRs, and that of the baseline MCP1 was 0.76. IL-6 levels at 3rd and 6th months during the treatment also showed AUROC values 0.85 and 0.78 respectively in predicting sustained VRs. CONCLUSION: Serum cytokine levels relfect the pathological differences of individual treatment phases and could also be useful in monitoring responses to peginterferon treatment in chronic hepatitis B patients.

  12. 白藜芦醇对高糖诱导内皮细胞损伤代谢记忆效应的研究%Effects of resveratrol on high glucose memory-induced injury to endothelial cell

    Institute of Scientific and Technical Information of China (English)

    丁慧; 王鹏; 王颜刚

    2014-01-01

    Cultured human umbilical vein endothelial cells (HUVECs) were divided and assigned to 6 groups:normal control group,mannitol control group,high glucose group,low dose resveratrol group,medium dose resveratrol group,and high dose resveratrol group.HUVECs were pretreated with or without 30 mmol/L glucose plus various concentrations of resveratrol (0.1,1,10 μmol/L) for 16 hours and then incubated with 5.5 mmol/L glucose for 6 days.The levels of vascular cell adhesion molecule 1 (VCAM-1),monocyte chemotactic protein 1 (MCP-1),and plasminogen activator inhibitor 1 (PAI-1) in the culture supernatant were measured by ELISA.NF-κB expression was detected by Western blot.Compared with normal glucose group,high glucose up-regulated the expression of NF-κB,along with the increased levels of VCAM-1,MCP-1,and PAI-1 (all P<0.05),which were still maintained at high levels even after withdrawal of high glucose.Resveratrol treatment down-regulated the expression of NF-κB and lowered the levels of VCAM-1,MCP-1,and PAI-1 (all P<0.05).These results suggest that resveratrol may decrease the secretion of VCAM-1,MCP-1,and PAI-1 and prevent high glucose memory-induced injury to endothelial cell via NF-κB pathway.%人脐静脉内皮细胞分为正常对照组、甘露醇对照组、高糖组和白藜芦醇低、中、高剂量组,细胞于30 mmol/L葡萄糖和0.1、1和10 μmol/L白藜芦醇培养16h后,再以5.5 mmol/L葡萄糖培养6d,应用ELISA法检测细胞培养上清中血管细胞黏附分子1(VCAM-1)、单核细胞趋化蛋白1(MCP-1)和纤溶酶原激活物抑制剂1(PAI-1)水平,以Western印迹法检测细胞内NF-κB蛋白表达.与正常对照组相比,高糖可诱导内皮细胞NF-κB表达上调(P<0.05),同时VCAM-1、MCP-1和PAI-1水平升高(均P<0.05),且在糖浓度恢复正常后仍持续上升.与高糖组相比,白藜芦醇预处理可以明显减少NF-κB表达,降低VCAM-1、MCP-1和PAI-1水平(均P<0.05).结果提示白藜芦醇可

  13. Green tea, black tea, and oolong tea polyphenols reduce visceral fat and inflammation in mice fed high-fat, high-sucrose obesogenic diets.

    Science.gov (United States)

    Heber, David; Zhang, Yanjun; Yang, Jieping; Ma, Janice E; Henning, Susanne M; Li, Zhaoping

    2014-09-01

    Green tea (GT) and caffeine in combination were shown to increase energy expenditure and fat oxidation, but less is known about the effects of black tea (BT) and oolong tea (OT). This study investigated whether decaffeinated polyphenol extracts from GT, BT, and OT decrease body fat and inflammation in male C57BL/6J mice fed high-fat/high-sucrose [HF/HS (32% energy from fat, 25% energy from sucrose)] diets. Mice were fed either an HF/HS diet with 0.25% of polyphenol from GT, OT, or BT or a low-fat/high-sucrose [LF/HS (10.6% energy from fat, 25% energy from sucrose)] diet for 20 wk. Monomeric tea polyphenols were found in the liver and adipose tissue of mice fed the HF/HS diet with GT polyphenols (GTPs) and OT polyphenols (OTPs) but not BT polyphenols (BTPs). Treatment with GTPs, OTPs, BTPs, and an LF/HS diet led to significantly lower body weight, total visceral fat volume by MRI, and liver lipid weight compared with mice in the HF/HS control group. Only GTPs reduced food intake significantly by ∼10%. GTP, BTP, and LF/HS-diet treatments significantly reduced serum monocyte chemotactic protein-1 (MCP-1) compared with HF/HS controls. In mesenteric fat, monocyte chemotactic protein-1 (Mcp1) gene expression was significantly decreased by treatment with GTPs, BTPs, OTPs, and an LF/HS diet and in liver tissue by GTP and BTP treatments. Mcp1 gene expression in epididymal fat was significantly decreased by the BTP and LF/HS diet interventions. In epididymal fat, consistent with an anti-inflammatory effect, adiponectin gene expression was significantly increased by GTPs and OTPs. Angiogenesis during adipose tissue expansion is anti-inflammatory by maintaining adipocyte perfusion. We observed significantly increased gene expression of vascular endothelial growth factor A by GTPs and vascular endothelial growth factor receptor 2 by BTPs and the LF/HS diet and a decrease in pigment epithelium-derived factor gene expression by OTPs and BTPs. In summary, all 3 tea polyphenol

  14. Identification, characterization and antigenicity of the Plasmodium vivax rhoptry neck protein 1 (PvRON1

    Directory of Open Access Journals (Sweden)

    Patarroyo Manuel E

    2011-10-01

    Full Text Available Abstract Background Plasmodium vivax malaria remains a major health problem in tropical and sub-tropical regions worldwide. Several rhoptry proteins which are important for interaction with and/or invasion of red blood cells, such as PfRONs, Pf92, Pf38, Pf12 and Pf34, have been described during the last few years and are being considered as potential anti-malarial vaccine candidates. This study describes the identification and characterization of the P. vivax rhoptry neck protein 1 (PvRON1 and examine its antigenicity in natural P. vivax infections. Methods The PvRON1 encoding gene, which is homologous to that encoding the P. falciparum apical sushi protein (ASP according to the plasmoDB database, was selected as our study target. The pvron1 gene transcription was evaluated by RT-PCR using RNA obtained from the P. vivax VCG-1 strain. Two peptides derived from the deduced P. vivax Sal-I PvRON1 sequence were synthesized and inoculated in rabbits for obtaining anti-PvRON1 antibodies which were used to confirm the protein expression in VCG-1 strain schizonts along with its association with detergent-resistant microdomains (DRMs by Western blot, and its localization by immunofluorescence assays. The antigenicity of the PvRON1 protein was assessed using human sera from individuals previously exposed to P. vivax malaria by ELISA. Results In the P. vivax VCG-1 strain, RON1 is a 764 amino acid-long protein. In silico analysis has revealed that PvRON1 shares essential characteristics with different antigens involved in invasion, such as the presence of a secretory signal, a GPI-anchor sequence and a putative sushi domain. The PvRON1 protein is expressed in parasite's schizont stage, localized in rhoptry necks and it is associated with DRMs. Recombinant protein recognition by human sera indicates that this antigen can trigger an immune response during a natural infection with P. vivax. Conclusions This study shows the identification and characterization of

  15. Roles oflow-density lipoprotein receptor-related protein 1 intumors

    Institute of Scientific and Technical Information of China (English)

    PeipeiXing; ZhichaoLiao; ZhiwuRen; JunZhao; FengjuSong; GuowenWang; KexinChen; Jilong Yang

    2016-01-01

    Low-density lipoprotein receptor-related protein 1 (LRP1, also known as CD91), a multifunctional endocytic and cell signaling receptor, is widely expressed on the surface of multiple cell types such as hepatocytes, ifbroblasts, neu-rons, astrocytes, macrophages, smooth muscle cells, and malignant cells. Emerging invitro and invivo evidence demonstrates that LRP1 is critically involved in many processes that drive tumorigenesis and tumor progression. For example, LRP1 not only promotes tumor cell migration and invasion by regulating matrix metalloproteinase (MMP)-2 and MMP-9 expression and functions but also inhibits cell apoptosis by regulating the insulin receptor, the serine/threonine protein kinase signaling pathway, and the expression of Caspase-3. LRP1-mediated phosphorylation of the extracellular signal-regulated kinase pathway and c-jun N-terminal kinase are also involved in tumor cell proliferation and invasion. In addition, LRP1 has been shown to be down-regulated by microRNA-205 and methylation ofLRP1 CpG islands. Furthermore, a novel fusion gene,LRP1-SNRNP25, promotes osteosarcoma cell invasion and migration. Only by understanding the mechanisms of these effects can we develop novel diagnostic and therapeutic strategies for cancers mediated by LRP1.

  16. Identification and characterization a novel transcription factor activator protein-1 in the sea cucumber Apostichopus japonicus.

    Science.gov (United States)

    Yang, Limeng; Li, Chenghua; Chang, Yaqing; Gao, Yinxue; Wang, Yi; Wei, Jing; Song, Jian; Sun, Ping

    2015-08-01

    The transcription factor activator protein-1 (AP-1) is an important gene expression regulator with typical Jun and region-leucine zipper (bZIP) domains and can respond to a plethora of physiological and pathological stimulus. In this study, we identified a novel AP-1 gene in Apostichopus japonicus by transcriptome sequencing and RACE approaches (designated as AjAP-1). The full-length of AjAP-1 was of 2944 bp including a 5' untranslated region (UTR) of 201 bp, a 3' UTR of 1753 bp and a putative open reading frame of 990 bp encoding a polypeptide of 329 amino acid residues. Two representative domains of Jun and bZIP as well as two nuclear localization signals (NLSs) were also detected in deduced amino acid of AjAP-1. Spatial distribution expression indicated that AjAP-1 was ubiquitously expressed in all examined tissues with predominant expression in the body wall, moderate in the tube feet, respiratory tree and colemocytes and slightly weak in the intestine and longitudinal muscle. Time-course expression analysis in intestine and coelomocytes revealed that AjAP-1 both reached its peak expression at 4 h after Vibrio splendidus challenge with a 2.6 and 8.2-fold increase compared to their control groups, respectively. Taken together, all these results suggested that AjAP-1 was a novel immune factor and might be involved in the processes of anti-bacteria response in sea cucumber. PMID:26093208

  17. Antibody to collapsin response mediator protein 1 promotes neurite outgrowth from rat hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    Hongsheng Lin; Jing Chen; Wenbin Zhang; Xiaobing Gong; Biao Chen; Guoqing Guo

    2011-01-01

    This study examined the role of collapsin response mediator protein 1 (CRMP-1) on neurite outgrowth from rat hippocampal neurons by blocking its function using an antibody. Hippocampal neurons, cultured in vitro, were treated (blocked) using a polyclonal antibody to CRMP-1, and neurite outgrowth and cytoskeletal changes w ere captured using atomic force microscopy and laser confocal microscopy. Control cells, treated with normal rabbit IgG, established their characteristic morphology and had a large number of processes emerging from the soma, including numerous branches. Microtubules were clearly visible in the soma, formed an elaborate network, and were aligned in parallel arrays to form bundles which projected into neurites. After blocking with CRMP-1 antibody, the number of branches emerging from axons and dendrites significantly increased and were substantially longer, compared with control cells. However, the microtubule network nearly disappeared and only a few remnants were visible. When CRMP-1 antibody-blocked neurons were treated with the Rho inhibitor, Y27632, numerous neurites emerged from the soma, and branches were more abundant than in control neurons. Although the microtubules were not as clearly visible compared with neurons cultured in control medium, the microtubule network recovered in cells treated with Y27632, when compared with cells that were blocked by CRMP-1 antibody (but not treated with Y27632). These results demonstrate that neurite outgrowth from hippocampal neurons can be promoted by blocking CRMP-1 with a polyclonal antibody.

  18. Circulating renalase, catecholamines, and vascular adhesion protein 1 in hypertensive patients.

    Science.gov (United States)

    Maciorkowska, Dominika; Zbroch, Edyta; Malyszko, Jolanta

    2015-11-01

    The aim of the study was to estimate and correlate circulating levels of renalase, vascular adhesion protein-1 (VAP-1), catecholamines in patients with primary hypertension. The renalase, VAP-1, and catecholamines concentration was estimated in 121 hypertensive patients. The correlation between renalase, VAP-1 levels and catecholamine concentration in blood, blood pressure control, pharmacological therapy, and medical history were taken in to consideration. The median office blood pressure was 145.5/86 mm Hg and was significantly higher than the median home blood pressure measurement value, which was 135/80 mm Hg, P hypertension comparing to healthy individuals (3.83 μg/mL and 248.37 ng/mL, P blood was observed (r = 0.549; P Hypertensive patients with diabetes mellitus had almost statistically significant higher VAP-1 concentration compared with hypertensive patients without diabetes mellitus (Me = 403.22 ng/mL vs. Me = 326,68 ng/mL, P = .064). In multiple regression analysis, renalase was predicted by plasma dopamine and norepinephrine as also diastolic office blood pressure and left ventricle ejection fraction. Circulating renalase and VAP-1 levels are elevated in patients with poor blood pressure control. Its correlation with noradrenalin concentration need further studies to find out the role of renalase as also VAP-1 in pathogenesis and treatment of hypertension. PMID:26403854

  19. Heterochromatin Protein 1 (HP1) Proteins Do Not Drive Pericentromeric Cohesin Enrichment in Human Cells

    Science.gov (United States)

    Serrano, Ángel; Rodríguez-Corsino, Miriam; Losada, Ana

    2009-01-01

    Sister chromatid cohesion mediated by cohesin is essential for accurate chromosome segregation. Classical studies suggest that heterochromatin promotes cohesion, but whether this happens through regulation of cohesin remains to be determined. Heterochromatin protein 1 (HP1) is a major component of heterochromatin. In fission yeast, the HP1 homologue Swi6 interacts with cohesin and is required for proper targeting and/or stabilization of cohesin at the centromeric region. To test whether this pathway is conserved in human cells, we have examined the behavior of cohesin in cells in which the levels of HP1 alpha, beta or gamma (the three HP1 proteins present in mammalian organisms) have been reduced by siRNA. We have also studied the consequences of treating human cells with drugs that change the histone modification profile of heterochromatin and thereby affect HP1 localization. Our results show no evidence for a requirement of HP1 proteins for either loading of bulk cohesin onto chromatin in interphase or retention of cohesin at pericentric heterochromatin in mitosis. However, depletion of HP1gamma leads to defects in mitotic progression. PMID:19352502

  20. Molecular cloning and subcellular localization of Tektin2-binding protein 1 (Ccdc 172) in rat spermatozoa.

    Science.gov (United States)

    Yamaguchi, Airi; Kaneko, Takane; Inai, Tetsuichiro; Iida, Hiroshi

    2014-04-01

    Tektins (TEKTs) are composed of a family of filament-forming proteins localized in cilia and flagella. Five types of mammalian TEKTs have been reported, all of which have been verified to be present in sperm flagella. TEKT2, which is indispensable for sperm structure, mobility, and fertilization, was present at the periphery of the outer dense fiber (ODF) in the sperm flagella. By yeast two-hybrid screening, we intended to isolate flagellar proteins that could interact with TEKT2, which resulted in the isolation of novel two genes from the mouse testis library, referred as a TEKT2-binding protein 1 (TEKT2BP1) and -protein 2 (TEKT2BP2). In this study, we characterized TEKT2BP1, which is registered as a coiled-coil domain-containing protein 172 (Ccdc172) in the latest database. RT-PCR analysis indicated that TEKT2BP1 was predominantly expressed in rat testis and that its expression was increased after 3 weeks of postnatal development. Immunocytochemical studies discovered that TEKT2BP1 localized in the middle piece of rat spermatozoa, predominantly concentrated at the mitochondria sheath of the flagella. We hypothesize that the TEKT2-TEKT2BP1 complex might be involved in the structural linkage between the ODF and mitochondria in the middle piece of the sperm flagella.

  1. Tumor necrosis factor-α-induced protein 1 and immunity to hepatitis B virus

    Institute of Scientific and Technical Information of China (English)

    Marie C Lin; Nikki P Lee; Ning Zheng; Pai-Hao Yang; Oscar G Wong; Hsiang-Fu Kung; Chee-Kin Hui; John M Luk; George Ka-Kit Lau

    2005-01-01

    AIM: To compare the gene expression profile in a pair of HBV-infected twins.METHODS: The gene expression profile was compared in a pair of HBV-infected twins.RESULTS: The twins displayed different disease outcomes. One acquired natural immunity against HBV,whereas the other became a chronic HBV carrier. Eightyeight and forty-six genes were found to be up- or downregulated in their PBMCs, respectively. Tumor necrosis factor-alpha-induced protein 1 (TNF-αIP1) that expressed at a higher level in the HBV-immune twins was identified and four pairs of siblings with HBV immunity by RTPCR. However, upon HBV core antigen stimulation,TNF-αIP1 was downregulated in PBMCs from subjects with immunity, whereas it was slightly upregulated in HBV carriers. Bioinformatics analysis revealed a K+channel tetramerization domain in TNF-αIP1 that shares a significant homology with some human, mouse, and C elegan proteins.CONCLUSION: TNF-αIP1 may play a role in the innate immunity against HBV.

  2. Huntingtin-associated protein 1 interacts with breakpoint cluster region protein to regulate neuronal differentiation.

    Directory of Open Access Journals (Sweden)

    Pai-Tsang Huang

    Full Text Available Alterations in microtubule-dependent trafficking and certain signaling pathways in neuronal cells represent critical pathogenesis in neurodegenerative diseases. Huntingtin (Htt-associated protein-1 (Hap1 is a brain-enriched protein and plays a key role in the trafficking of neuronal surviving and differentiating cargos. Lack of Hap1 reduces signaling through tropomyosin-related kinases including extracellular signal regulated kinase (ERK, resulting in inhibition of neurite outgrowth, hypothalamic dysfunction and postnatal lethality in mice. To examine how Hap1 is involved in microtubule-dependent trafficking and neuronal differentiation, we performed a proteomic analysis using taxol-precipitated microtubules from Hap1-null and wild-type mouse brains. Breakpoint cluster region protein (Bcr, a Rho GTPase regulator, was identified as a Hap1-interacting partner. Bcr was co-immunoprecipitated with Hap1 from transfected neuro-2a cells and co-localized with Hap1A isoform more in the differentiated than in the nondifferentiated cells. The Bcr downstream effectors, namely ERK and p38, were significantly less activated in Hap1-null than in wild-type mouse hypothalamus. In conclusion, Hap1 interacts with Bcr on microtubules to regulate neuronal differentiation.

  3. Dynamin like protein 1 participated in the hemoglobin uptake pathway of Plasmodium falciparum

    Institute of Scientific and Technical Information of China (English)

    ZHOU Hong-chang; GAO Yu-hui; ZHONG Xiang; WANG Heng

    2009-01-01

    Background During the blood stage of malaria infection, parasites internalize in the host red blood cells and degrade massive amounts of hemoglobin for their development. Although the morphology of the parasite's hemoglobin uptake pathway has been clearly observed, little has been known about its molecular mechanisms. Methods The recombinant proteins from Plasmodium falciparum, dynamin like protein 1 (PfDYN1) and 2 (PfDYN2) GTPase domain, were expressed in E .coli and showed GTPase activity. By using a dynamin inhibitor, dynasore, we demonstrated the involvement of PfDYN1 in the hemoglobin uptake pathway. Results The GTPase activity of the two recombinant proteins was inhibited by dynasore in vitro. Treatment of parasite cultures with 80 μmol/L dynasore at the ring and early trophozoite stage resulted in substantial inhibition of parasite growth and in an obvious decline of hemoglobin quantum. Furthermore, reduced intraceliular hemozoin accumulation and decreased uptake of the FITC-dextran were also observed, together with distinctive changes in the ultrastructure of parasites after the dynasore treatment. Conclusions Our results show that PfDYN1 plays an important role in the hemoglobin uptake pathway of P. Falciparum and suggest its possibility of being a novel target for malaria chemotherapy.

  4. Evaluation of salivary gland protein 1 antibodies in patients with primary and secondary Sjogren's syndrome.

    Science.gov (United States)

    Shen, Long; Kapsogeorgou, Efstathia K; Yu, Meixing; Suresh, Lakshmanan; Malyavantham, Kishore; Tzioufas, Anthanasios G; Ambrus, Julian L

    2014-11-01

    Sjogren's syndrome (SS) has been associated with the expression of anti-Ro and anti-La antibodies. Anti-salivary gland protein 1 (SP1) antibodies have recently been identified in patients with SS. The current work involved a cross sectional study to determine whether anti-SP1 antibodies were identified in particular subgroups of patients with SS. The results of this study revealed that anti-SP1 antibodies were present in the sera of 52% of SS patients while anti-Ro/anti-La was present in 63% of patients. 19% of patients had anti-SP1 without anti-Ro/anti-La. Patients with SS and lymphoma expressed anti-Ro, anti-La and anti-SP1 together. In SS associated with RA, 50% had antibodies anti-SP1 while 40% had anti-Ro/anti-La. In conclusion, anti-SP1 antibodies are commonly seen in both primary and secondary SS and rarely in normal controls. Future studies are needed to determine the roles and timing of expression of anti-SP1 antibodies in Sjogren's syndrome.

  5. Nuclear translocation of EGF receptor regulated by Epstein-Barr virus encoded latent membrane protein 1

    Institute of Scientific and Technical Information of China (English)

    TAO; Yongguang; SONG; Xin; TAN; Yunnian; LIN; Xiaofeng; ZH

    2004-01-01

    Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is considered to be the major oncogenic protein of EBV encoded proteins, and also it has always been the core of the oncogenic mechanism of EBV. Traditional receptor theory demonstrates that cell surface receptors exert biological functions on the membrane, which neither enter into the nucleus nor directly affect the transcription of the target genes. But, advanced studies on nuclear translocation of the epidermal growth factor receptor (EGFR) family have greatly developed our knowledge of the biological function of cell surface receptors. In this study, we used Tet-on LMP1 HNE2 cell line as a cell model, which is a dual-stable LMP1 integrated NPC cell line and the expression of LMP1 in which could be regulated by Tet system. We found that LMP1 could regulate the nuclear translocation of EGFR in a dose-dependent manner from both quantitative and qualitative levels through the Western blot analysis and the immunofluorescent analysis with a laser scanning confocal microscope. We further demonstrated that the nuclear localization sequence of EGFR played some roles in the location of the protein within the nucleus under LMP1 regulation, and the nuclear accumulation of EGFR regulated by LMP1 was in a ligand-independent manner. These findings provide a novel view that the regulation of LMP1 on the nuclear translocation of EGFR is critical for the process of nasopharyngeal carcinoma.

  6. LDL Receptor-Related Protein-1 (LRP1 Regulates Cholesterol Accumulation in Macrophages.

    Directory of Open Access Journals (Sweden)

    Anna P Lillis

    Full Text Available Within the circulation, cholesterol is transported by lipoprotein particles and is taken up by cells when these particles associate with cellular receptors. In macrophages, excessive lipoprotein particle uptake leads to foam cell formation, which is an early event in the development of atherosclerosis. Currently, mechanisms responsible for foam cell formation are incompletely understood. To date, several macrophage receptors have been identified that contribute to the uptake of modified forms of lipoproteins leading to foam cell formation, but the in vivo contribution of the LDL receptor-related protein 1 (LRP1 to this process is not known [corrected]. To investigate the role of LRP1 in cholesterol accumulation in macrophages, we generated mice with a selective deletion of LRP1 in macrophages on an LDL receptor (LDLR-deficient background (macLRP1-/-. After feeding mice a high fat diet for 11 weeks, peritoneal macrophages isolated from Lrp+/+ mice contained significantly higher levels of total cholesterol than those from macLRP1-/- mice. Further analysis revealed that this was due to increased levels of cholesterol esters. Interestingly, macLRP1-/- mice displayed elevated plasma cholesterol and triglyceride levels resulting from accumulation of large, triglyceride-rich lipoprotein particles in the circulation. This increase did not result from an increase in hepatic VLDL biosynthesis, but rather results from a defect in catabolism of triglyceride-rich lipoprotein particles in macLRP1-/- mice. These studies reveal an important in vivo contribution of macrophage LRP1 to cholesterol homeostasis.

  7. The multidrug resistance-associated protein 1 transports methoxychlor and protects the seminiferous epithelium from injury.

    Science.gov (United States)

    Tribull, Tiffany E; Bruner, Richard H; Bain, Lisa J

    2003-04-30

    We examined the ability of the multidrug resistance-associated protein 1 (MRP1/ABCC1) to transport pesticides, as this transporter mediates the cellular efflux of a variety of xenobiotics, typically as glucuronide, sulfate, or glutathione conjugates. NIH3T3 cells stably expressing MRP1 were 3.37-fold more resistant to the toxicity of fenitrothion, 3.12-fold more resistant to chlorpropham, and 2.5-fold more resistant to methoxychlor, a pesticide with estrogenic and anti-androgenic metabolites. The cells expressing MRP1 also eliminated methoxychlor two times more rapidly than their mock-transfected counterparts. We then examined whether mrp1 expression could alter the toxicity of methoxychlor in vivo using male FVB/mrp1 knockout mice (FVB/mrp1-/-). Both control and knockout mice were fed 25 mg/kg methoxychlor in honey for 39 days, and its effects on testicular morphology were examined. Methoxychlor treatment did not significantly affect testicular morphology in the FVB mice, but markedly reduced the number of developing spermatocytes in the FVB/mrp1-/- mice. These results suggest that MRPI may play a role in protecting the seminiferous tubules from methoxychlor-induced damage.

  8. Latent membrane protein 1 inhibits apoptosis induced by 60 irradiation via Survivin triggering signal-pathway

    International Nuclear Information System (INIS)

    Objective: To investigate the anti-apoptosis mechanism of EB virus encoden latent membrane protein 1 (LMP1) via the survivin signal transduction pathway after irradiation induction. Methods: Tet-on- LMP1 HNE2 cells, as a model, were detected with morphological assay, flowcytometry and Caspase 3 assay after 60Co irradiation with LMP1 induced by doxycycline. The apoptosis in the anti-sense survivin transfected cells was tested. Results: The results showed that, with LMP1 expression, the apoptosis rates from morphological assay and flowcytometry were 32.7%±2.1% and 6.3%, which showed that they were all lower than that without LMP1 expression (66.0%±3.0% and 29.6%). When anti-sense of survivin was induced, the apoptosis rates were 59.0%±3.2% and 3.0% respectively, and caspase 3 activity was 3.78 nmol/106 cells, which were higher than that of the control (26.0%±2.6%, 8.6% and 2.79 nmol/106). Survivin restrained the cell apoptosis induced by irradiation, but anti-sense of survivin could release this inhibition of cell apoptosis triggered by LMP1 expression. Conclusion: LMP1 inhibits the irradiation-induced cell apoptosis via triggering survivin expression. Survivin may be targeted in some certain therapy

  9. Activator protein 1 (Fos/Jun) functions in inflammatory bone and skin disease.

    Science.gov (United States)

    Zenz, Rainer; Eferl, Robert; Scheinecker, Clemens; Redlich, Kurt; Smolen, Josef; Schonthaler, Helia B; Kenner, Lukas; Tschachler, Erwin; Wagner, Erwin F

    2008-01-01

    Activator protein 1 (AP-1) (Fos/Jun) is a transcriptional regulator composed of members of the Fos and Jun families of DNA binding proteins. The functions of AP-1 were initially studied in mouse development as well as in the whole organism through conventional transgenic approaches, but also by gene targeting using knockout strategies. The importance of AP-1 proteins in disease pathways including the inflammatory response became fully apparent through conditional mutagenesis in mice, in particular when employing gene inactivation in a tissue-specific and inducible fashion. Besides the well-documented roles of Fos and Jun proteins in oncogenesis, where these genes can function both as tumor promoters or tumor suppressors, AP-1 proteins are being recognized as regulators of bone and immune cells, a research area termed osteoimmunology. In the present article, we review recent data regarding the functions of AP-1 as a regulator of cytokine expression and an important modulator in inflammatory diseases such as rheumatoid arthritis, psoriasis and psoriatic arthritis. These new data provide a better molecular understanding of disease pathways and should pave the road for the discovery of new targets for therapeutic applications.

  10. Cell biological characterization of the malaria vaccine candidate trophozoite exported protein 1.

    Directory of Open Access Journals (Sweden)

    Caroline Kulangara

    Full Text Available In a genome-wide screen for alpha-helical coiled coil motifs aiming at structurally defined vaccine candidates we identified PFF0165c. This protein is exported in the trophozoite stage and was named accordingly Trophozoite exported protein 1 (Tex1. In an extensive preclinical evaluation of its coiled coil peptides Tex1 was identified as promising novel malaria vaccine candidate providing the rational for a comprehensive cell biological characterization of Tex1. Antibodies generated against an intrinsically unstructured N-terminal region of Tex1 and against a coiled coil domain were used to investigate cytological localization, solubility and expression profile. Co-localization experiments revealed that Tex1 is exported across the parasitophorous vacuole membrane and located to Maurer's clefts. Change in location is accompanied by a change in solubility: from a soluble state within the parasite to a membrane-associated state after export to Maurer's clefts. No classical export motifs such as PEXEL, signal sequence/anchor or transmembrane domain was identified for Tex1.

  11. Surveillance of artemether-lumefantrine associated Plasmodium falciparum multidrug resistance protein-1 gene polymorphisms in Tanzania

    DEFF Research Database (Denmark)

    Kavishe, Reginald A; Paulo, Petro; Kaaya, Robert D;

    2014-01-01

    BACKGROUND: Resistance to anti-malarials is a major public health problem worldwide. After deployment of artemisinin-based combination therapy (ACT) there have been reports of reduced sensitivity to ACT by malarial parasites in South-East Asia. In Tanzania, artemether-lumefantrine (ALu) is the re......BACKGROUND: Resistance to anti-malarials is a major public health problem worldwide. After deployment of artemisinin-based combination therapy (ACT) there have been reports of reduced sensitivity to ACT by malarial parasites in South-East Asia. In Tanzania, artemether-lumefantrine (ALu......) is the recommended first-line drug in treatment of uncomplicated malaria. This study surveyed the distribution of the Plasmodium falciparum multidrug resistance protein-1 single nucleotide polymorphisms (SNPs) associated with increased parasite tolerance to ALu, in Tanzania. METHODS: A total of 687 Plasmodium...... of common Pfmdr1 haplotypes reflecting strict implementation of ALu policy in Tanzania with overall prevalence of NFD haplotype ranging from 17 to 26% among other haplotypes. With continuation of ALu as first-line drug this haplotype is expected to keep rising, thus there is need for continued...

  12. Stimulation of IGF-binding protein-1 secretion by AMP-activated protein kinase.

    Science.gov (United States)

    Lewitt, M S

    2001-04-20

    Insulin-like growth factor-binding protein-1 (IGFBP-1) is stimulated during intensive exercise and in catabolic conditions to very high concentrations, which are not completely explained by known regulators such as insulin and glucocorticoids. The role of AMP-activated protein kinase (AMPK), an important signaling system in lipid and carbohydrate metabolism, in regulating IGFBP-1 was studied in H4-II-E rat hepatoma cells. Arsenic(III) oxide and 5-aminoimidazole-4-carboxamide-riboside (AICAR) were used as activators. AICAR (150 microM) stimulated IGFBP-1 secretion twofold during a 5-h incubation (P = 0.002). Insulin (100 ng/ml) inhibited IGFBP-1 by 80% (P < 0.001), but this was completely abolished in the presence of 150 microM AICAR. The effect of dexamethasone in stimulating IGFBP-1 threefold was additive to the effect of AICAR (P < 0.001) and, in the presence of AICAR, was incompletely inhibited by insulin. In conclusion AMPK is identified as a novel regulatory pathway for IGFBP-1, stimulating secretion and blocking the inhibitory effect of insulin. PMID:11302732

  13. The role of vitamin D3 upregulated protein 1 in thioacetamide-induced mouse hepatotoxicity

    International Nuclear Information System (INIS)

    Thioacetamide (TA) is a commonly used drug that can trigger acute hepatic failure (AHF) through generation of oxidative stress. Vitamin D3 upregulated protein 1 (VDUP1) is an endogenous inhibitor of thioredoxin, a ubiquitous thiol oxidoreductase, that regulates cellular redox status. In this study, we investigated the role of VDUP1 in AHF using a TA-induced liver injury model. VDUP1 knockout (KO) and wild-type (WT) mice were subjected to a single intraperitoneal TA injection, and various parameters of hepatic injury were assessed. VDUP1 KO mice displayed a significantly higher survival rate, lower serum alanine aminotransferase and aspartate aminotransferase levels, and less hepatic damage, compared to WT mice. In addition, induction of apoptosis was decreased in VDUP1 KO mice, with the alteration of caspase-3 and -9 activities, Bax-to-Bcl-2 expression ratios, and mitogen activated protein kinase (MAPK) signaling pathway. Importantly, analysis of TA bioactivation revealed lower plasma clearance of TA and covalent binding of [14C]TA to liver macromolecules in VDUP1 KO mice. Furthermore, the level of oxidative stress was significantly less in VDUP1 KO mice than in their WT counterparts, as evident from lipid peroxidation assay. These results collectively indicate that VDUP1 deficiency protects against TA-induced acute liver injury via lower bioactivation of TA and antioxidant effects.

  14. Fatty acid binding protein 1 is related with development of aspirin-exacerbated respiratory disease.

    Directory of Open Access Journals (Sweden)

    Tae-Hoon Kim

    Full Text Available BACKGROUND: Aspirin-exacerbated respiratory disease (AERD refers to the development of bronchoconstriction in asthmatics following the ingestion of aspirin. Although alterations in eicosanoid metabolites play a role in AERD, other immune or inflammatory mechanisms may be involved. We aimed to identify proteins that were differentially expressed in nasal polyps between patients with AERD and aspirin-tolerant asthma (ATA. METHODOLOGY/PRINCIPAL FINDINGS: Two-dimensional electrophoresis was adopted for differential display proteomics. Proteins were identified by liquid chromatography-tandem mass spectrometry (LC-MS. Western blotting and immunohistochemical staining were performed to compare the amount of fatty acid-binding protein 1 (FABP1 in the nasal polyps of patients with AERD and ATA. Fifteen proteins were significantly up- (seven spots or down-regulated in the nasal polyps of patients with AERD (n = 5 compared to those with ATA (n = 8. LC-MS revealed an increase in seven proteins expression and a decrease in eight proteins expression in patients with AERD compared to those with ATA (P = 0.003-0.045. FABP1-expression based on immunoblotting and immunohistochemical analysis was significantly higher in the nasal polyps of patients with AERD compared to that in patients with ATA. FABP1 was observed in epithelial, eosinophils, macrophages, and the smooth-muscle cells of blood vessels in the polyps. CONCLUSIONS/SIGNIFICANCE: Our results indicate that alterations in 15 proteins, including FABP1, may be related to the development of AERD.

  15. Expression of Yes-associated protein 1 gene and protein in oral squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    LI Song-ying; HU Ji-an; WANG Hui-ming

    2013-01-01

    Background Oral squamous cell carcinoma (OSCC) is one of the most common malignancies in the oral and maxillofaoial region.Yes-associated protein 1 (YAP1) has been implicated as a bona fide oncogene in solid tumors.We seek to elucidate the role of YAP1 in OSCC tissue.Methods We identified YAP1 gene and protein overexpression in 30 OSCC patients and 10 normal oral mucosa tissues by immunohistochemistry,Western blotting and reverse transcription polymerase chain reaction (RT-PCR).Results In the normal oral mucosa by immunohistochemical staining,YAP1 mainly located in both the cytoplasm and nucleus mainly the nuclei of the basal cells.In OSCC,the expression of YAP1 translocated from the nucleus to cytoplasm;YAP1 being mainly located in both the cytoplasm and nucleus of the adjacent mucosa.The expression of YAP1 gradual increased in normal oral mucosa,tumor adjacent mucosa and low grade,middle grade,high grade OSCC tissue by Western blotting.Significant difference was found between the expressions of the normal oral mucosa and OSCC tissue (P <0.05).The coincidence was detected between the normal oral mucosa and OSCC tissue by RT-PCR (P <0.05).Conclusions YAP1 is involved in the carcinogenesis and development of OSCC.There is a transformation between nucleus and cytoplasm.

  16. Overexpression of vascular adhesion protein-1 is associated with poor prognosis of astrocytomas.

    Science.gov (United States)

    Kostoro, Joanna; Chang, Shu-Jyuan; Clark Lai, Yen-Chang; Wu, Chun-Chieh; Chai, Chee-Yin; Kwan, Aij-Lie

    2016-06-01

    Vascular adhesion protein-1 (VAP-1) is one of the endothelial adhesion molecules that is believed to play a role in tumor progression and metastasis, supporting cancer cell extravasation. Very few studies have been performed on analyzing the contribution of VAP-1 in brain tumor. Astrocytomas are the most common type of brain tumors, which are classified by World Health Organization (WHO) into four grades according to the degree of malignancy. This study was designed to investigate VAP-1 expression level in different astrocytoma grades and its correlation with clinicopathological features as well as prognosis of astrocytoma patients. Eighty-seven patients with different grades of astrocytoma (WHO Grade I-Grade IV) were enrolled in this study. The expression of VAP-1 was assayed by immunohistochemistry. The correlation between VAP-1 expression and clinicopathological features was evaluated by Chi-square test, and overall survival was analyzed by Kaplan-Meier method. Cox regression analysis was applied to analyze the independent influence of each parameter on overall survival. The expression level of VAP-1 was significantly higher in diffuse astrocytoma than those of pilocytic astrocytoma (p astrocytoma and VAP-1(low) tumors in pilocytic astrocytoma (p astrocytoma. PMID:26935340

  17. Targeted deletion of fibrinogen like protein 1 reveals a novel role in energy substrate utilization.

    Directory of Open Access Journals (Sweden)

    Valeriy Demchev

    Full Text Available Fibrinogen like protein 1(Fgl1 is a secreted protein with mitogenic activity on primary hepatocytes. Fgl1 is expressed in the liver and its expression is enhanced following acute liver injury. In animals with acute liver failure, administration of recombinant Fgl1 results in decreased mortality supporting the notion that Fgl1 stimulates hepatocyte proliferation and/or protects hepatocytes from injury. However, because Fgl1 is secreted and detected in the plasma, it is possible that the role of Fgl1 extends far beyond its effect on hepatocytes. In this study, we show that Fgl1 is additionally expressed in brown adipose tissue. We find that signals elaborated following liver injury also enhance the expression of Fgl1 in brown adipose tissue suggesting that there is a cross talk between the injured liver and adipose tissues. To identify extra hepatic effects, we generated Fgl1 deficient mice. These mice exhibit a phenotype suggestive of a global metabolic defect: Fgl1 null mice are heavier than wild type mates, have abnormal plasma lipid profiles, fasting hyperglycemia with enhanced gluconeogenesis and exhibit differences in white and brown adipose tissue morphology when compared to wild types. Because Fgl1 shares structural similarity to Angiopoietin like factors 2, 3, 4 and 6 which regulate lipid metabolism and energy utilization, we postulate that Fgl1 is a member of an emerging group of proteins with key roles in metabolism and liver regeneration.

  18. Differential Expression of Motility-Related Protein-1 Gene in Gastric Cancer and Its Premalignant Lesions

    Institute of Scientific and Technical Information of China (English)

    YaoXu; JieZheng; WentianLiu; JunXing; YanyunLi; XinGeng; WeimingZhang

    2004-01-01

    OBJECTIVE To identify genes related to gastric cancer and to analyze their expression profiles in different gastric tissues. METHODS The differentially expressed cDNA bands were assayed by fluorescent differential display from gastric cancer specimens, matched with normal gastric mucosa and premalignant lesions. The motility-related protein-1 (MRP-1/CD9) gene expression was studied by Northern blots and reverse transcription polymerase chain reaction (RT-PCR) in different kinds of gastric tissue. RESULTS A differentially expressed cDNA fragment showed lower expression in all gastric cancers compared to the normal gastric mucosa and premalignant lesions; and it was found to be homologous to the MRP-1/CD9 gene. Northern blot analysis confirmed the differential expression. RT-PCR analysis showed that the MRP-1/CD9 gene was expressed at a much lower rate in gastric cancers (0.31 +0.18) compared to the matched normal gastric tissue (0.49+0.24) and premalignant lesions (0.47+0.18)(P<0.05). Furthermore, its expression in intestinal-type of gastric cancer (0.38+0.16) was higher than that expressed in a diffuse-type of gastric cancer (0.22±0.17)(P<0.05). CCONCLUSION The MRP-1/CD9 gene expression was down-regulated in gastric cancer and its expression may be related to the carcinogenic process and histological type of gastric cancer.

  19. Cysteine-rich protein 1 (CRP1 regulates actin filament bundling

    Directory of Open Access Journals (Sweden)

    Fraley Tamara S

    2005-12-01

    Full Text Available Abstract Background Cysteine-rich protein 1 (CRP1 is a LIM domain containing protein localized to the nucleus and the actin cytoskeleton. CRP1 has been demonstrated to bind the actin-bundling protein α-actinin and proposed to modulate the actin cytoskeleton; however, specific regulatory mechanisms have not been identified. Results CRP1 expression increased actin bundling in rat embryonic fibroblasts. Although CRP1 did not affect the bundling activity of α-actinin, CRP1 was found to stabilize the interaction of α-actinin with actin bundles and to directly bundle actin microfilaments. Using confocal and photobleaching fluorescence resonance energy transfer (FRET microscopy, we demonstrate that there are two populations of CRP1 localized along actin stress fibers, one associated through interaction with α-actinin and one that appears to bind the actin filaments directly. Consistent with a role in regulating actin filament cross-linking, CRP1 also localized to the membrane ruffles of spreading and PDGF treated fibroblasts. Conclusion CRP1 regulates actin filament bundling by directly cross-linking actin filaments and stabilizing the interaction of α-actinin with actin filament bundles.

  20. Human heterochromatin protein 1 isoforms regulate androgen receptor signaling in prostate cancer.

    Science.gov (United States)

    Itsumi, Momoe; Shiota, Masaki; Yokomizo, Akira; Kashiwagi, Eiji; Takeuchi, Ario; Tatsugami, Katsunori; Inokuchi, Junichi; Song, Yoohyun; Uchiumi, Takeshi; Naito, Seiji

    2013-06-01

    Androgen receptor (AR) signaling is critical for the tumorigenesis and development of prostate cancer, as well as the progression to castration-resistant prostate cancer. We previously showed that the heterochromatin protein 1 (HP1) β isoform plays a critical role in transactivation of AR signaling as an AR coactivator that promotes prostate cancer cell proliferation. However, the roles of other HP1 isoforms, HP1α and HP1γ, in AR expression and prostate cancer remain unclear. Here, we found that knockdown of HP1γ, but not HP1α, reduced AR expression and cell proliferation by inducing cell cycle arrest at G1 phase in LNCaP cells. Conversely, overexpression of full-length HP1α and its C-terminal deletion mutant increased AR expression and cell growth, whereas overexpression of HP1γ had no effect. Similarly, HP1α overexpression promoted 22Rv1 cell growth, whereas HP1γ knockdown reduced the proliferation of CxR cells, a castration-resistant LNCaP derivative. Taken together, HP1 isoforms distinctly augment AR signaling and cell growth in prostate cancer. Therefore, silencing of HP1β and HP1γ may be a promising therapeutic strategy for treatment of prostate cancer.

  1. Effect of Acupuncture on Uncoupling Protein 1 Gene Expression for Brown Adipose Tissue of Obese Rats

    Institute of Scientific and Technical Information of China (English)

    刘志诚; 孙凤岷; 赵东红; 张中成; 孙志; 吴海涛; 徐炳国; 朱苗花; 李朝军

    2003-01-01

    Objective: To explore the effects of acupuncture on the expression of uncoupling protein 1(UCP1) gene of brown adipose tissue (BAT) in obese rats. Methods: The expression of UCP1 gene of BAT was determined with RT-PCR technique. The changes of body weight, Lee′s index, body fat, and the expression of UCP1 gene of BAT in obese rats were observed before and after acupuncture. Resuits:The body weight, Lee′s index, body fat in obese rats were all markedly higher than those in normal rats,but the expression of UCP1 gene of BAT in obese rats was all lower than that in normal rats. There were negative correlation between the obesity index and the expression of UCP1 gene in BAT. After acupuncture the marked effect of weight loss was achieved while the expression of UCP1 gene of BAT obviously increased in obese rats. Conclusion: The abnormal reduction for expression of UCP1 gene of BAT might be an important cause for the obesity. To promote the expression of UCP1 in obese organism might be an important cellular and molecular mechanism in anti-obesity effect by acupuncture.

  2. Heterochromatin protein 1 (HP1 proteins do not drive pericentromeric cohesin enrichment in human cells.

    Directory of Open Access Journals (Sweden)

    Angel Serrano

    Full Text Available Sister chromatid cohesion mediated by cohesin is essential for accurate chromosome segregation. Classical studies suggest that heterochromatin promotes cohesion, but whether this happens through regulation of cohesin remains to be determined. Heterochromatin protein 1 (HP1 is a major component of heterochromatin. In fission yeast, the HP1 homologue Swi6 interacts with cohesin and is required for proper targeting and/or stabilization of cohesin at the centromeric region. To test whether this pathway is conserved in human cells, we have examined the behavior of cohesin in cells in which the levels of HP1 alpha, beta or gamma (the three HP1 proteins present in mammalian organisms have been reduced by siRNA. We have also studied the consequences of treating human cells with drugs that change the histone modification profile of heterochromatin and thereby affect HP1 localization. Our results show no evidence for a requirement of HP1 proteins for either loading of bulk cohesin onto chromatin in interphase or retention of cohesin at pericentric heterochromatin in mitosis. However, depletion of HP1gamma leads to defects in mitotic progression.

  3. Anabolic Properties of High Mobility Group Box Protein-1 in Human Periodontal Ligament Cells In Vitro

    Directory of Open Access Journals (Sweden)

    Michael Wolf

    2014-01-01

    Full Text Available High mobility group box protein-1 (HMGB1 is mainly recognized as a chemoattractant for macrophages in the initial phase of host response to pathogenic stimuli. However, recent findings provide evidence for anabolic properties in terms of enhanced proliferation, migration, and support of wound healing capacity of mesenchymal cells suggesting a dual role of the cytokine in the regulation of immune response and subsequent regenerative processes. Here, we examined potential anabolic effects of HMGB1 on human periodontal ligament (PDL cells in the regulation of periodontal remodelling, for example, during orthodontic tooth movement. Preconfluent human PDL cells (hPDL were exposed to HMGB1 protein and the influence on proliferation, migration, osteogenic differentiation, and biomineralization was determined by MTS assay, real time PCR, immunofluorescence cytochemistry, ELISA, and von Kossa staining. HMGB1 protein increased hPDL cell proliferation, migration, osteoblastic marker gene expression, and protein production as well as mineralized nodule formation significantly. The present findings support the dual character of HMGB1 with anabolic therapeutic potential that might support the reestablishment of the structural and functional integrity of the periodontium following periodontal trauma such as orthodontic tooth movement.

  4. Rotavirus nonstructural protein 1 antagonizes innate immune response by interacting with retinoic acid inducible gene I

    Directory of Open Access Journals (Sweden)

    Qin Lan

    2011-12-01

    Full Text Available Abstract Background The nonstructural protein 1 (NSP1 of rotavirus has been reported to block interferon (IFN signaling by mediating proteasome-dependent degradation of IFN-regulatory factors (IRFs and (or the β-transducin repeat containing protein (β-TrCP. However, in addition to these targets, NSP1 may subvert innate immune responses via other mechanisms. Results The NSP1 of rotavirus OSU strain as well as the IRF3 binding domain truncated NSP1 of rotavirus SA11 strain are unable to degrade IRFs, but can still inhibit host IFN response, indicating that NSP1 may target alternative host factor(s other than IRFs. Overexpression of NSP1 can block IFN-β promoter activation induced by the retinoic acid inducible gene I (RIG-I, but does not inhibit IFN-β activation induced by the mitochondrial antiviral-signaling protein (MAVS, indicating that NSP1 may target RIG-I. Immunoprecipitation experiments show that NSP1 interacts with RIG-I independent of IRF3 binding domain. In addition, NSP1 induces down-regulation of RIG-I in a proteasome-independent way. Conclusions Our findings demonstrate that inhibition of RIG-I mediated type I IFN responses by NSP1 may contribute to the immune evasion of rotavirus.

  5. A Computational Approach towards the Understanding of Plasmodium falciparum Multidrug Resistance Protein 1.

    Science.gov (United States)

    Patel, Saumya K; George, Linz-Buoy; Prasanth Kumar, Sivakumar; Highland, Hyacinth N; Jasrai, Yogesh T; Pandya, Himanshu A; Desai, Ketaki R

    2013-01-01

    The emergence of drug resistance in Plasmodium falciparum tremendously affected the chemotherapy worldwide while the intense distribution of chloroquine-resistant strains in most of the endemic areas added more complications in the treatment of malaria. The situation has even worsened by the lack of molecular mechanism to understand the resistance conferred by Plasmodia species. Recent studies have suggested the association of antimalarial resistance with P. falciparum multidrug resistance protein 1 (PfMDR1), an ATP-binding cassette (ABC) transporter and a homologue of human P-glycoprotein 1 (P-gp1). The present study deals about the development of PfMDR1 computational model and the model of substrate transport across PfMDR1 with insights derived from conformations relative to inward- and outward-facing topologies that switch on/off the transportation system. Comparison of ATP docked positions and its structural motif binding properties were found to be similar among other ATPases, and thereby contributes to NBD domains dimerization, a unique structural agreement noticed in Mus musculus Pgp and Escherichia coli MDR transporter homolog (MsbA). The interaction of leading antimalarials and phytochemicals within the active pocket of both wild-type and mutant-type PfMDR1 demonstrated the mode of binding and provided insights of less binding affinity thereby contributing to parasite's resistance mechanism. PMID:25937947

  6. Nucleation of apatite crystals in vitro by self-assembled dentin matrix protein 1

    Science.gov (United States)

    He, Gen; Dahl, Tom; Veis, Arthur; George, Anne

    2003-08-01

    Bones and teeth are biocomposites that require controlled mineral deposition during their self-assembly to form tissues with unique mechanical properties. Acidic extracellular matrix proteins play a pivotal role during biomineral formation. However, the mechanisms of protein-mediated mineral initiation are far from understood. Here we report that dentin matrix protein 1 (DMP1), an acidic protein, can nucleate the formation of hydroxyapatite in vitro in a multistep process that begins by DMP1 binding calcium ions and initiating mineral deposition. The nucleated amorphous calcium phosphate precipitates ripen and nanocrystals form. Subsequently, these expand and coalesce into microscale crystals elongated in the c-axis direction. Characterization of the functional domains in DMP1 demonstrated that intermolecular assembly of acidic clusters into a β-sheet template was essential for the observed mineral nucleation. Protein-mediated initiation of nanocrystals, as discussed here, might provide a new methodology for constructing nanoscale composites by self-assembly of polypeptides with tailor-made peptide sequences.

  7. Analysis of Antibodies Directed against Merozoite Surface Protein 1 of the Human Malaria Parasite Plasmodium falciparum

    Science.gov (United States)

    Woehlbier, Ute; Epp, Christian; Kauth, Christian W.; Lutz, Rolf; Long, Carole A.; Coulibaly, Boubacar; Kouyaté, Bocar; Arevalo-Herrera, Myriam; Herrera, Sócrates; Bujard, Hermann

    2006-01-01

    The 190-kDa merozoite surface protein 1 (MSP-1) of Plasmodium falciparum, an essential component in the parasite's life cycle, is a primary candidate for a malaria vaccine. Rabbit antibodies elicited by the heterologously produced MSP-1 processing products p83, p30, p38, and p42, derived from strain 3D7, were analyzed for the potential to inhibit in vitro erythrocyte invasion by the parasite and parasite growth. Our data show that (i) epitopes recognized by antibodies, which inhibit parasite replication, are distributed throughout the entire MSP-1 molecule; (ii) when combined, antibodies specific for different regions of MSP-1 inhibit in a strictly additive manner; (iii) anti-MSP-1 antibodies interfere with erythrocyte invasion as well as with the intraerythrocytic growth of the parasite; and (iv) antibodies raised against MSP-1 of strain 3D7 strongly cross-inhibit replication of the heterologous strain FCB-1. Accordingly, anti-MSP-1 antibodies appear to be capable of interfering with parasite multiplication at more than one level. Since the overall immunogenicity profile of MSP-1 in rabbits closely resembles that found in sera of Aotus monkeys immunized with parasite-derived MSP-1 and of humans semi-immune to malaria from whom highly inhibiting antigen-specific antibodies were recovered, we consider the findings reported here to be relevant for the development of MSP-1-based vaccines against malaria. PMID:16428781

  8. Nuclear overexpression of metastasis-associated protein 1 correlates significantly with poor survival in nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Li Wen-Fei

    2012-04-01

    Full Text Available Abstract Background Metastasis-associated protein 1 (MTA1 has been associated with poor prognosis in several malignant carcinomas. The purpose of this study was to investigate the expression and prognostic value of MTA1 in nasopharyngeal carcinoma (NPC. Methods MTA1 expression was assessed using immunohistochemistry in paraffin-embedded tumor specimens from 208 untreated NPC patients. Cox regression analysis was used to calculate the hazard ratio (HR, 95% confidence interval (CI and identify independent prognostic factors, and recursive partitioning analysis was used to create a decision tree. Results Nuclear overexpression of MTA1 was observed in 48.6% (101/208 of the NPC tissues. Nuclear overexpression of MTA1 correlated positively with N classification (P = 0.02, clinical stage (P = 0.04, distant metastasis (P P = 0.01. Additionally, nuclear overexpression of MTA1 correlated significantly with poorer distant metastasis-free survival (DMFS; P P P = 0.02 and poorer OS (HR, 1.98; 95% CI, 1.09–3.59; P = 0.03. Using recursive partitioning analysis, the NPC patients could be classified with a low, intermediate or high risk of distant metastasis and death, on the basis of clinical stage, age and MTA1 expression. Conclusion The results of this study suggest that nuclear overexpression of MTA1 correlates significantly with poorer DMFS and poorer OS in NPC. MTA1 has potential as a novel prognostic biomarker in NPC.

  9. Specific interaction with cardiolipin triggers functional activation of Dynamin-Related Protein 1.

    Directory of Open Access Journals (Sweden)

    Itsasne Bustillo-Zabalbeitia

    Full Text Available Dynamin-Related Protein 1 (Drp1, a large GTPase of the dynamin superfamily, is required for mitochondrial fission in healthy and apoptotic cells. Drp1 activation is a complex process that involves translocation from the cytosol to the mitochondrial outer membrane (MOM and assembly into rings/spirals at the MOM, leading to membrane constriction/division. Similar to dynamins, Drp1 contains GTPase (G, bundle signaling element (BSE and stalk domains. However, instead of the lipid-interacting Pleckstrin Homology (PH domain present in the dynamins, Drp1 contains the so-called B insert or variable domain that has been suggested to play an important role in Drp1 regulation. Different proteins have been implicated in Drp1 recruitment to the MOM, although how MOM-localized Drp1 acquires its fully functional status remains poorly understood. We found that Drp1 can interact with pure lipid bilayers enriched in the mitochondrion-specific phospholipid cardiolipin (CL. Building on our previous study, we now explore the specificity and functional consequences of this interaction. We show that a four lysine module located within the B insert of Drp1 interacts preferentially with CL over other anionic lipids. This interaction dramatically enhances Drp1 oligomerization and assembly-stimulated GTP hydrolysis. Our results add significantly to a growing body of evidence indicating that CL is an important regulator of many essential mitochondrial functions.

  10. Nonstructural protein 1 characteristic peak from NS1-saliva mixture with Surface-Enhanced Raman spectroscopy.

    Science.gov (United States)

    Radzol, A R M; Lee, Khuan Y; Mansor, W

    2013-01-01

    Surface Enhanced Raman spectroscopy (SERS) is an enhanced technique of Raman spectroscopy, which amplifies the intensity of Raman scattering to a practical range with adsorption of analyte onto nano-size plasmonic material such as gold, silver or copper. This feature of SERS has given it a niche in tracing molecular structure, especially useful for marking diseases specific biomarker. NS1 protein has been clinically accepted as an alternative biomarker for diseases caused by flavivirus. Detection of Nonstructural Protein 1 (NS1) will allow early diagnosis of the diseases. Its presence in the blood serum has been reported as early as first day of infection. With gold substrate, our work here intends to explore if SERS is suitable to detect NS1 from saliva, with saliva becoming the most favored alternative to blood as diagnostic fluid due to its advantages in sample collection. Our experimental results find both gold coated slide (GS) and saliva being Raman inactive, but the molecular fingerprint of NS1 protein at Raman shift 1012 cm(-1), which has never been reported before. The distinct peak is discovered to be attributed by breathing vibration of the benzene ring structure of NS1 side chain molecule. The characteristic peak is also found to vary in direct proportion to concentration of the NS1-saliva mixture, with a correlation coefficient of +0.96118 and a standard error estimation of 0.11382.

  11. Behavioral analysis of the huntingtin-associated protein 1 ortholog trak-1 in Caenorhabditis elegans.

    Science.gov (United States)

    Norflus, Fran; Bu, Jingnan; Guyton, Evon; Gutekunst, Claire-Anne

    2016-09-01

    The precise role of huntingtin-associated protein 1 (HAP1) is not known, but studies have shown that it is important for early development and survival. A Caenorhabditis elegans ortholog of HAP1, T27A3.1 (also called trak-1), has been found and is expressed in a subset of neurons. Potential behavioral functions of three knockout lines of T27A3.1 were examined. From its suspected role in mice we hypothesize that T27A3.1 might be involved in egg hatching and early growth, mechanosensation, chemosensation, sensitivity to osmolarity, and synaptic transmission. Our studies show that the knockout worms are significantly different from the wild-type (WT) worms only in the synaptic transmission test, which was measured by adding aldicarb, an acetylcholinesterase inhibitor. The change in function was determined by measuring the number of worms paralyzed. However, when the T27A3.1 worms were tested for egg hatching and early growth, mechanosensation, chemosensation, and sensitivity to osmolarity, there were no significant differences between the knockout and WT worms. © 2016 Wiley Periodicals, Inc. PMID:27319755

  12. BRCA-associated protein 1 mutant cholangiocarcinoma: an aggressive disease subtype

    Science.gov (United States)

    Al-Shamsi, Humaid O.; Anand, Deepa; Shroff, Rachna T.; Jain, Apurva; Zuo, Mingxin; Conrad, Claudius; Vauthey, Jean-Nicolas

    2016-01-01

    Background BRCA-associated protein 1, an enzyme encoded by the BAP1 gene, is commonly mutated in uveal melanoma, mesothelioma, and renal cancers. Tumors with BAP1 mutation follow an aggressive course. BAP1 mutations have also been observed in cholangiocarcinoma (CCA). The clinical phenotype of BAP1 mutant CCA may yield useful prognostic and therapeutic information but has not been defined. Methods The records of CCA patients who underwent next-generation sequencing (NGS) were reviewed, and data on clinical, histopathological, genetic, and radiological features; response to therapy; time to progression; and survival were analyzed. Results Twenty-two cases of BAP1-mutation associated CCA were diagnosed from January 1, 2009, to February 1, 2015, at our center. Twenty patients had intrahepatic CCA and two had extrahepatic CCA. Tumor sizes (largest dimension) ranged from 2 to 16 cm (mean, 8.5 cm). Twelve patients had tumors that were poorly differentiated. Majority of the patients had advanced disease at presentation and 13 had bone metastases. Thirteen patients (59%) experienced rapidly progressive disease following primary therapy (chemotherapy or surgical resection). The mean time to tumor progression was 3.8 months after the first line chemotherapy. Conclusions BAP1 mutation in CCA may be associated with aggressive disease and poor response to standard therapies. Therefore, BAP1-targeted therapies need to be investigated. PMID:27563445

  13. The Y-Box Binding Protein 1 Suppresses Alzheimer's Disease Progression in Two Animal Models.

    Directory of Open Access Journals (Sweden)

    N V Bobkova

    Full Text Available The Y-box binding protein 1 (YB-1 is a member of the family of DNA- and RNA binding proteins. It is involved in a wide variety of DNA/RNA-dependent events including cell proliferation and differentiation, stress response, and malignant cell transformation. Previously, YB-1 was detected in neurons of the neocortex and hippocampus, but its precise role in the brain remains undefined. Here we show that subchronic intranasal injections of recombinant YB-1, as well as its fragment YB-11-219, suppress impairment of spatial memory in olfactory bulbectomized (OBX mice with Alzheimer's type degeneration and improve learning in transgenic 5XFAD mice used as a model of cerebral amyloidosis. YB-1-treated OBX and 5XFAD mice showed a decreased level of brain β-amyloid. In OBX animals, an improved morphological state of neurons was revealed in the neocortex and hippocampus; in 5XFAD mice, a delay in amyloid plaque progression was observed. Intranasally administered YB-1 penetrated into the brain and could enter neurons. In vitro co-incubation of YB-1 with monomeric β-amyloid (1-42 inhibited formation of β-amyloid fibrils, as confirmed by electron microscopy. This suggests that YB-1 interaction with β-amyloid prevents formation of filaments that are responsible for neurotoxicity and neuronal death. Our data are the first evidence for a potential therapeutic benefit of YB-1 for treatment of Alzheimer's disease.

  14. Vitamin D represses dentin matrix protein 1 in cementoblasts and osteocytes.

    Science.gov (United States)

    Nociti, F H; Foster, B L; Tran, A B; Dunn, D; Presland, R B; Wang, L; Bhattacharyya, N; Collins, M T; Somerman, M J

    2014-02-01

    Calcium and phosphorus homeostasis is achieved by interplay among hormones, including 1,25(OH)2D3 (1,25D), parathyroid hormone, and fibroblast growth factor 23 (FGF23), and their interactions with other proteins. For example, mutations in dentin matrix protein 1 (DMP-1) result in increased FGF23 and hypophosphatemic rickets. 1,25D is reported to modulate FGF23; thus, we hypothesized that 1,25D may be involved in modulating DMP-1 in an intermediary step. Murine cementoblasts (OCCM-30) and osteocyte-like cells (MLO-Y4 and MLO-A5), known to express DMP-1, were used to analyze effects of 1,25D on DMP-1 expression in vitro. DMP-1 mRNA levels decreased by 50% (p < .05) in the presence of 1,25D in all cell types, while use of a vitamin D receptor (VDR) agonist (EB1089) and antagonist (23S,25S)-DLAM-2P confirmed that VDR pathway activation was required for this response. Further analysis showed that histone deacetylase recruitment was necessary, but neither protein kinase A nor C pathways were required. In conclusion, our results support the hypothesis that 1,25D regulates DMP-1 expression through a VDR-dependent mechanism, possibly contributing to local changes in bone/tooth mineral homeostasis. PMID:24334408

  15. Analysis of antibodies directed against merozoite surface protein 1 of the human malaria parasite Plasmodium falciparum.

    Science.gov (United States)

    Woehlbier, Ute; Epp, Christian; Kauth, Christian W; Lutz, Rolf; Long, Carole A; Coulibaly, Boubacar; Kouyaté, Bocar; Arevalo-Herrera, Myriam; Herrera, Sócrates; Bujard, Hermann

    2006-02-01

    The 190-kDa merozoite surface protein 1 (MSP-1) of Plasmodium falciparum, an essential component in the parasite's life cycle, is a primary candidate for a malaria vaccine. Rabbit antibodies elicited by the heterologously produced MSP-1 processing products p83, p30, p38, and p42, derived from strain 3D7, were analyzed for the potential to inhibit in vitro erythrocyte invasion by the parasite and parasite growth. Our data show that (i) epitopes recognized by antibodies, which inhibit parasite replication, are distributed throughout the entire MSP-1 molecule; (ii) when combined, antibodies specific for different regions of MSP-1 inhibit in a strictly additive manner; (iii) anti-MSP-1 antibodies interfere with erythrocyte invasion as well as with the intraerythrocytic growth of the parasite; and (iv) antibodies raised against MSP-1 of strain 3D7 strongly cross-inhibit replication of the heterologous strain FCB-1. Accordingly, anti-MSP-1 antibodies appear to be capable of interfering with parasite multiplication at more than one level. Since the overall immunogenicity profile of MSP-1 in rabbits closely resembles that found in sera of Aotus monkeys immunized with parasite-derived MSP-1 and of humans semi-immune to malaria from whom highly inhibiting antigen-specific antibodies were recovered, we consider the findings reported here to be relevant for the development of MSP-1-based vaccines against malaria.

  16. The AUXIN BINDING PROTEIN 1 is required for differential auxin responses mediating root growth.

    Directory of Open Access Journals (Sweden)

    Alexandre Tromas

    Full Text Available BACKGROUND: In plants, the phytohormone auxin is a crucial regulator sustaining growth and development. At the cellular level, auxin is interpreted differentially in a tissue- and dose-dependent manner. Mechanisms of auxin signalling are partially unknown and the contribution of the AUXIN BINDING PROTEIN 1 (ABP1 as an auxin receptor is still a matter of debate. METHODOLOGY/PRINCIPAL FINDINGS: Here we took advantage of the present knowledge of the root biological system to demonstrate that ABP1 is required for auxin response. The use of conditional ABP1 defective plants reveals that the protein is essential for maintenance of the root meristem and acts at least on the D-type CYCLIN/RETINOBLASTOMA pathway to control entry into the cell cycle. ABP1 affects PLETHORA gradients and confers auxin sensitivity to root cells thus defining the competence of the cells to be maintained within the meristem or to elongate. ABP1 is also implicated in the regulation of gene expression in response to auxin. CONCLUSIONS/SIGNIFICANCE: Our data support that ABP1 is a key regulator for root growth and is required for auxin-mediated responses. Differential effects of ABP1 on various auxin responses support a model in which ABP1 is the major regulator for auxin action on the cell cycle and regulates auxin-mediated gene expression and cell elongation in addition to the already well known TIR1-mediated ubiquitination pathway.

  17. Molecular cloning and subcellular localization of Tektin2-binding protein 1 (Ccdc 172) in rat spermatozoa.

    Science.gov (United States)

    Yamaguchi, Airi; Kaneko, Takane; Inai, Tetsuichiro; Iida, Hiroshi

    2014-04-01

    Tektins (TEKTs) are composed of a family of filament-forming proteins localized in cilia and flagella. Five types of mammalian TEKTs have been reported, all of which have been verified to be present in sperm flagella. TEKT2, which is indispensable for sperm structure, mobility, and fertilization, was present at the periphery of the outer dense fiber (ODF) in the sperm flagella. By yeast two-hybrid screening, we intended to isolate flagellar proteins that could interact with TEKT2, which resulted in the isolation of novel two genes from the mouse testis library, referred as a TEKT2-binding protein 1 (TEKT2BP1) and -protein 2 (TEKT2BP2). In this study, we characterized TEKT2BP1, which is registered as a coiled-coil domain-containing protein 172 (Ccdc172) in the latest database. RT-PCR analysis indicated that TEKT2BP1 was predominantly expressed in rat testis and that its expression was increased after 3 weeks of postnatal development. Immunocytochemical studies discovered that TEKT2BP1 localized in the middle piece of rat spermatozoa, predominantly concentrated at the mitochondria sheath of the flagella. We hypothesize that the TEKT2-TEKT2BP1 complex might be involved in the structural linkage between the ODF and mitochondria in the middle piece of the sperm flagella. PMID:24394471

  18. Improved crystallization and diffraction of caffeine-induced death suppressor protein 1 (Cid1)

    Energy Technology Data Exchange (ETDEWEB)

    Yates, Luke A., E-mail: luke@strubi.ox.ac.uk; Durrant, Benjamin P.; Barber, Michael; Harlos, Karl [University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Fleurdépine, Sophie; Norbury, Chris J. [University of Oxford, South Parks Road, Oxford OX1 3RE (United Kingdom); Gilbert, Robert J. C., E-mail: luke@strubi.ox.ac.uk [University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom)

    2015-02-21

    The use of truncation and RNA-binding mutations of caffeine induced death suppressor protein 1 (Cid1) as a means to enhance crystallogenesis leading to an improvement of X-ray diffraction resolution by 1.5 Å is reported. The post-transcriptional addition of uridines to the 3′-end of RNAs is an important regulatory process that is critical for coding and noncoding RNA stability. In fission yeast and metazoans this untemplated 3′-uridylylation is catalysed by a single family of terminal uridylyltransferases (TUTs) whose members are adapted to specific RNA targets. In Schizosaccharomyces pombe the TUT Cid1 is responsible for the uridylylation of polyadenylated mRNAs, targeting them for destruction. In metazoans, the Cid1 orthologues ZCCHC6 and ZCCHC11 uridylate histone mRNAs, targeting them for degradation, but also uridylate microRNAs, altering their maturation. Cid1 has been studied as a model TUT that has provided insights into the larger and more complex metazoan enzyme system. In this paper, two strategies are described that led to improvements both in the crystallogenesis of Cid1 and in the resolution of diffraction by ∼1.5 Å. These advances have allowed high-resolution crystallo@@graphic studies of this TUT system to be initiated.

  19. FGF21-Mediated Improvements in Glucose Clearance Require Uncoupling Protein 1

    Directory of Open Access Journals (Sweden)

    Michelle M. Kwon

    2015-11-01

    Full Text Available Fibroblast growth factor 21 (FGF21-mediated weight loss and improvements in glucose metabolism correlate with increased uncoupling protein 1 (Ucp1 levels in adipose tissues, suggesting that UCP1-dependent thermogenesis may drive FGF21 action. It was reported that FGF21 is equally effective at reducing body weight and improving glucose homeostasis without UCP1. We find while FGF21 can lower body weight in both wild-type and Ucp1 knockout mice, rapid clearance of glucose by FGF21 is defective in the absence of UCP1. Furthermore, in obese wild-type mice there is a fall in brown adipose tissue (BAT temperature during glucose excursion, and FGF21 improves glucose clearance while preventing the fall in BAT temperature. In Ucp1 knockout mice, the fall in BAT temperature during glucose excursion and FGF21-mediated changes in BAT temperature are lost. We conclude FGF21-mediated improvements in clearance of a glucose challenge require UCP1 and evoke UCP1-dependent thermogenesis as a method to increase glucose disposal.

  20. Subcellular compartmentalization of docking protein-1 contributes to progression in colorectal cancer.

    Science.gov (United States)

    Friedrich, Teresa; Söhn, Michaela; Gutting, Tobias; Janssen, Klaus-Peter; Behrens, Hans-Michael; Röcken, Christoph; Ebert, Matthias P A; Burgermeister, Elke

    2016-06-01

    Full-length (FL) docking protein-1 (DOK1) is an adapter protein which inhibits growth factor and immune response pathways in normal tissues, but is frequently lost in human cancers. Small DOK1 variants remain in cells of solid tumors and leukemias, albeit, their functions are elusive. To assess the so far unknown role of DOK1 in colorectal cancer (CRC), we generated DOK1 mutants which mimic the domain structure and subcellular distribution of DOK1 protein variants in leukemia patients. We found that cytoplasmic DOK1 activated peroxisome-proliferator-activated-receptor-gamma (PPARγ) resulting in inhibition of the c-FOS promoter and cell proliferation, whereas nuclear DOK1 was inactive. PPARγ-agonist increased expression of endogenous DOK1 and interaction with PPARγ. Forward translation of this cell-based signaling model predicted compartmentalization of DOK1 in patients. In a large series of CRC patients, loss of DOK1 protein was associated with poor prognosis at early tumor stages (*p=0.001; n=1492). In tumors with cytoplasmic expression of DOK1, survival was improved, whereas nuclear localization of DOK1 correlated with poor outcome, indicating that compartmentalization of DOK1 is critical for CRC progression. Thus, DOK1 was identified as a prognostic factor for non-metastatic CRC, and, via its drugability by PPARγ-agonist, may constitute a potential target for future cancer treatments. PMID:27428427

  1. [Expression of cyclin-dependent kinase 2-associated protein 1 in chicken embryos of different sexes].

    Science.gov (United States)

    Yang, Yu; Feng, Yan-Ping; Gong, Ping; Huang, Pan; Li, Shi-Jun; Peng, Xiu-Li; Gong, Yan-Zhang

    2009-09-01

    To investigate the expression and functions of cyclin-dependent kinase 2-associated protein 1 (cdk2ap1) screened by suppression subtractive hybridization in chicken embryo development, a pair of primers was designed to amplify the cdk2ap1 fragment by RT-PCR and subsequently the fragment obtained was cloned into the plasmid pGEM-T. Sense and antisense probes labeled with digoxigenin were generated using SP6 and T7 RNA polymerases, respectively, and used to examine cdk2ap1 expression in chicken embryos of both sexes by whole-mount in situ hybridization. In both sexes, cdk2ap1 was expressed in the head mesenchyme, rhombencephalon, optic vesicles, spinal neural tube, and forelimb of 4.0-day-old embryos and the expression in males was significantly higher than that in females. In addition, in the genital ridge and hindlimb of the 4.0-day-old chicken embryo, cdk2ap1 was obviously expressed in the males but not in females. It is supposed that cdk2ap1 may play a role in the sexual differentiation and development of gonad of chicken embryo. PMID:19819846

  2. Sex-Specific Protection of Osteoarthritis by Deleting Cartilage Acid Protein 1.

    Directory of Open Access Journals (Sweden)

    Xianpeng Ge

    Full Text Available Cartilage acidic protein 1 (CRTAC1 was recently identified as an elevated protein in the synovial fluid of patients with osteoarthritis (OA by a proteomic analysis. This gene is also upregulated in both human and mouse OA by transcriptomic analysis. The objective of this study was to characterize the expression and function of CRTAC1 in OA. Here, we first confirm the increase of CRTAC1 in cartilage biopsies from OA patients undergoing joint replacement by real-time PCR and immunohistochemistry. Furthermore, we report that proinflammatory cytokines interleukin-1beta and tumor necrosis factor alpha upregulate CRTAC1 expression in primary human articular chondrocytes and synovial fibroblasts. Genetic deletion of Crtac1 in mice significantly inhibited cartilage degradation, osteophyte formation and gait abnormalities of post-traumatic OA in female, but not male, animals undergoing the destabilization of medial meniscus (DMM surgery. Taken together, CRTAC1 is upregulated in the osteoarthritic joint and directly induced in chondrocytes and synovial fibroblasts by pro-inflammatory cytokines. This molecule is necessary for the progression of OA in female mice after DMM surgery and thus represents a potential therapy for this prevalent disease, especially for women who demonstrate higher rates and more severe OA.

  3. High-mobility group box protein 1 promotes the survival of myeloid-derived suppressor cells by inducing autophagy.

    Science.gov (United States)

    Parker, Katherine H; Horn, Lucas A; Ostrand-Rosenberg, Suzanne

    2016-09-01

    Myeloid-derived suppressor cells are immune-suppressive cells that are elevated in most individuals with cancer, where their accumulation and suppressive activity are driven by inflammation. As myeloid-derived suppressor cells inhibit anti-tumor immunity and promote tumor progression, we are determining how their viability is regulated. Previous studies have established that the damage-associated molecular pattern molecule high-mobility group box protein 1 drives myeloid-derived suppressor cell accumulation and suppressive potency and is ubiquitously present in the tumor microenvironment. As high-mobility group box protein 1 also facilitates tumor cell survival by inducing autophagy, we sought to determine if high-mobility group box protein 1 regulates myeloid-derived suppressor cell survival through induction of autophagy. Inhibition of autophagy increased the quantity of apoptotic myeloid-derived suppressor cells, demonstrating that autophagy extends the survival and increases the viability of myeloid-derived suppressor cells. Inhibition of high-mobility group box protein 1 similarly increased the level of apoptotic myeloid-derived suppressor cells and reduced myeloid-derived suppressor cell autophagy, demonstrating that in addition to inducing the accumulation of myeloid-derived suppressor cells, high-mobility group box protein 1 sustains myeloid-derived suppressor cell viability. Circulating myeloid-derived suppressor cells have a default autophagic phenotype, and tumor-infiltrating myeloid-derived suppressor cells are more autophagic, consistent with the concept that inflammatory and hypoxic conditions within the microenvironment of solid tumors contribute to tumor progression by enhancing immune-suppressive myeloid-derived suppressor cells. Overall, these results demonstrate that in addition to previously recognized protumor effects, high-mobility group box protein 1 contributes to tumor progression by increasing myeloid-derived suppressor cell viability by

  4. Dengue Virus Nonstructural Protein 1 Induces Vascular Leakage through Macrophage Migration Inhibitory Factor and Autophagy

    Science.gov (United States)

    Chen, Hong-Ru; Chuang, Yung-Chun; Lin, Yee-Shin; Liu, Hsiao-Sheng; Liu, Ching-Chuan; Perng, Guey-Chuen

    2016-01-01

    Dengue virus (DENV) is the most common mosquito-borne flavivirus; it can either cause mild dengue fever or the more severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). One of the characteristic features of DHF/DSS is vascular leakage; although DENV nonstructural protein 1 (NS1) has been proved to induce vascular leakage after binding to Toll-like receptor 4, the down-stream mechanism has not yet been fully understood. In the sera of DENV-infected patients, the concentrations of DENV NS1 and inflammatory cytokine macrophage migration inhibitory factor (MIF) are positively correlated with disease severity, but whether DENV NS1 induces vascular leakage through MIF secretion remains unknown. We demonstrated that recombinant NS1 induced vascular leakage and MIF secretion both in human endothelial cell line HMEC-1 and in mice. Furthermore, these phenomena were inhibited in the presence of anti-NS1 antibodies both in vitro and in vivo. DENV NS1 also induced LC3-I to LC3-II conversion and p62 degradation in endothelial cell line, which indicated the formation of autophagy. To clarify whether MIF or autophagy mediated DENV NS1-induced vascular leakage, various inhibitors were applied. The results showed that DENV NS1-induced vascular leakage and VE-cadherin disarray were blocked in the presence of MIF inhibitors, anti-MIF-antibodies or autophagy inhibitors. An Atg5 knockdown clone further confirmed that autophagy formation of endothelial cells was required in NS1-induced vascular leakage. Furthermore, DENV NS1-induced LC3 puncta were also decreased in the presence of MIF inhibitors, indicating that MIF mediated DENV NS1-induced autophagy. Taken together, the results suggest a potential mechanism of DENV-induced vascular leakage and provide possible therapeutic targets against DHF/DSS. PMID:27409803

  5. Plasmodium falciparum Merozoite Surface Protein-1 Polymorphisms among Asymptomatic Sickle Cell Anemia Patients in Nigeria.

    Science.gov (United States)

    Bamidele Abiodun, Iwalokun; Oluwadun, Afolabi; Olugbenga Ayoola, Aina; Senapon Olusola, Iwalokun

    2016-01-01

    Asymptomatic malaria (ASM) has been implicated in the development of hemolytic crisis in infected sickle cell anemia (SCA) patients worldwide. This study surveyed steady state SCA Nigerian patients for ASM to investigate the influence of malaria prevention behaviors and age on parasitaemia and multiplicity of infection (MOI). A total of 78 steady SCA patients aged 5 - 27 years on routine care at three health facilities in Lagos were investigated for ASM by light microscopy and PCR with a multiplicity of infection determined by genotyping block 2 of merozoite surface protein 1 (msp1) gene of Plasmodium falciparum (P. falciparum). Use of malaria prevention measures was captured using a semi-structured questionnaire. The prevalence rates of ASM (due to Pf only) by microscopy and PCR were found to be 27.3% and 47.4% respectively (P < 0.05) with a Mean + SEM parasite density of 2238.4 + 464.3 parasites/uL. Five distinct msp1 genotypes [K1 (2), MAD20 (2), RO33 (1)] were detected and significant (P<0.05) disparity in allele frequencies (K1, 91.8%, MAD20, 32.4%; RO33, 18.9%) was found. The overall MOI was 1.43 and 37.8% of infections were polyclonal (P<0.05). ASM was associated with non-use of preventive measures and occurred in 62.1% of SCA patients aged < 10y with lower MOI of 1.3 compared to 38.1% in older patients with a higher MOI of 1.5 (P<0.05). We conclude that PCR improved the diagnosis of ASM among Nigerian SCA patients with infections being of low complexity and associated with non-use of preventive interventions and R033 msp1 allele selection. PMID:26853290

  6. Plasmodium falciparum Merozoite Surface Protein-1 Polymorphisms among Asymptomatic Sickle Cell Anemia Patients in Nigeria

    Directory of Open Access Journals (Sweden)

    Iwalokun Bamidele Abiodun

    2016-01-01

    Full Text Available Asymptomatic malaria (ASM has been implicated in the development of hemolytic crisis in infected sickle cell anemia (SCA patients worldwide. This study surveyed steady state SCA Nigerian patients for ASM to investigate the influence of malaria prevention behaviors and age on parasitaemia and multiplicity of infection (MOI. A total of 78 steady SCA patients aged 5 – 27 years on routine care at three health facilities in Lagos were investigated for ASM by light microscopy and PCR with a multiplicity of infection determined by genotyping block 2 of merozoite surface protein 1 (msp1 gene of Plasmodium falciparum (P. falciparum. Use of malaria prevention measures was captured using a semi-structured questionnaire. The prevalence rates of ASM (due to Pf only by microscopy and PCR were found to be 27.3% and 47.4% respectively (P < 0.05 with a Mean + SEM parasite density of 2238.4 + 464.3 parasites/uL. Five distinct msp1 genotypes [K1 (2, MAD20 (2, RO33 (1] were detected and significant (P<0.05 disparity in allele frequencies (K1, 91.8%, MAD20, 32.4%; RO33, 18.9% was found. The overall MOI was 1.43 and 37.8% of infections were polyclonal (P<0.05. ASM was associated with non-use of preventive measures and occurred in 62.1% of SCA patients aged < 10y with lower MOI of 1.3 compared to 38.1% in older patients with a higher MOI of 1.5 (P<0.05. We conclude that PCR improved the diagnosis of ASM among Nigerian SCA patients with infections being of low complexity and associated with non-use of preventive interventions and R033 msp1 allele selection.

  7. Molecular cloning and ontogenesis expression of fatty acid transport protein-1 in yellow-feathered broilers

    Institute of Scientific and Technical Information of China (English)

    Yuzhen Song; Jiaying Feng; Lihua Zhou; Gang Shu; Xiaotong Zhu; Ping Gao; Yongliang Zhang; Qingyan Jiang

    2008-01-01

    Fatty acid transport protein-1 (FATP-1) is one of the important transporter proteins involved in fatty acid transmembrane transport and fat deposition. To study the relationship between FATP-1 mRNA expression and fat deposition, chicken (Gallus gallus) FATP-1 sequence was first cloned by rapid amplification of cDNA ends (RACE). Tissue samples of chest muscle, leg muscle, subcutaneous fat, and abdominal fat were collected from six male and six female broilers each, at 22 days, 29 days, and 42 days, respectively. The tissue specificity and ontogenesis expression pattern of the FATP-1 mRNA of yellow-feathered broilers was studied by real-time reverse transcription polymerase chain reaction (RT-PCR), and the fat deposition laws in different tissues were also compared. A 2,488 bp cDNA sequence of chicken FATP-1 was cloned by RACE (GenBank accession no. DQ352834), including 547 bp 3' end untranslated region (URT) and 1,941 bp open reading frame (ORF). Chicken FATP-1 encoded 646 amino acid residues, which shared 83.9% and 83.0% identity with those of human and rat, respectively. The results of quantitative PCR demonstrated a constant FATP-1 mRNA expression level in the chest muscle and subcutaneous fat of both male and female broilers at three stages, whereas the expression level of the FATP-1 mRNA in the leg muscle at 42 days was significantly higher than that at 22 days or 29 days. In the abdominal fat of male broilers, the gene expression significantly increased with age, whereas the female broilers showed a dramatic downregulation of FATP-1 expression in abdominal fat at 42 days. This suggested a typical tissue-and gender-specific expression pattern of chicken FATP-1, mediating the specific process of fatty acid transport or utilization in muscle and adipose tissues.

  8. Expression, purification and mass spectrometric analysis of LIM mineralization protein-1 in human lung epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Sreedhara Sangadala; Louisa Titus; Scott D. Boden

    2008-01-01

    LIM mineralization protein-1 (LMP-1) is a novel osteoin ductive protein that has been cloned and shown to induce bone formation both in vitro and in vivo. Detection and evaluation of the possible presence of carbohydrate structures in LMP-1 is an important regulatory consideration for the therapeutic use of recombinantly expressed protein. The sequence of LMP-1 contains a highly conserved N-terminal PDZ domain and three C-terminal LIM domains. The sequence analysis of LMP-I predicts two potential N-glycosylation sites and several O-glycosylation sites. Here, we report the cloning and overexpression of LMP.1 in human lung carcinoma(A549) cells. Even though our group already reported the sequence of LMP-1 cDNA, we undertook this work to clarify whether or not the overexpressed protein undergoes any glycosylation in vivo. The expressed full-length recombinant protein was purified and subjected to chemical analysis and internal sequencing. The absence of any hexosamines (Nacetyl glucosamine or N-acetyl galactosamine) in chemical composition analysis of LMP.I protein revealed that there is little or no post-translational glycosylation of the LMP-1 polypeptide in lung carcinoma cells (A549). We performed in-gel trypsin digestion on purified LMP-I, and the resulting peptide digests were analyzed further using matrix.assisted laser desorption and ionization mass spectrometry for peptide mass finger printing, which produced several exact matches with the corresponding LMP-1 peptides. Separation by high performance liquid chromatography and purification of the desired peptides followed by N-terminal sequencing resulted in many exact LMP-1 matches for several purified peptides, thus establishing the identity of the purified protein as LMP-1.

  9. Hematopoietic protein-1 regulates the actin membrane skeleton and membrane stability in murine erythrocytes.

    Directory of Open Access Journals (Sweden)

    Maia M Chan

    Full Text Available Hematopoietic protein-1 (Hem-1 is a hematopoietic cell specific member of the WAVE (Wiskott-Aldrich syndrome verprolin-homologous protein complex, which regulates filamentous actin (F-actin polymerization in many cell types including immune cells. However, the roles of Hem-1 and the WAVE complex in erythrocyte biology are not known. In this study, we utilized mice lacking Hem-1 expression due to a non-coding point mutation in the Hem1 gene to show that absence of Hem-1 results in microcytic, hypochromic anemia characterized by abnormally shaped erythrocytes with aberrant F-actin foci and decreased lifespan. We find that Hem-1 and members of the associated WAVE complex are normally expressed in wildtype erythrocyte progenitors and mature erythrocytes. Using mass spectrometry and global proteomics, Coomassie staining, and immunoblotting, we find that the absence of Hem-1 results in decreased representation of essential erythrocyte membrane skeletal proteins including α- and β- spectrin, dematin, p55, adducin, ankyrin, tropomodulin 1, band 3, and band 4.1. Hem1⁻/⁻ erythrocytes exhibit increased protein kinase C-dependent phosphorylation of adducin at Ser724, which targets adducin family members for dissociation from spectrin and actin, and subsequent proteolysis. Increased adducin Ser724 phosphorylation in Hem1⁻/⁻ erythrocytes correlates with decreased protein expression of the regulatory subunit of protein phosphatase 2A (PP2A, which is required for PP2A-dependent dephosphorylation of PKC targets. These results reveal a novel, critical role for Hem-1 in the homeostasis of structural proteins required for formation and stability of the actin membrane skeleton in erythrocytes.

  10. Expression of activator protein-1 (AP-1) family members in breast cancer

    International Nuclear Information System (INIS)

    The activator protein-1 (AP-1) transcription factor is believed to be important in tumorigenesis and altered AP-1 activity was associated with cell transformation. We aimed to assess the potential role of AP-1 family members as novel biomarkers in breast cancer. We studied the expression of AP-1 members at the mRNA level in 72 primary breast tumors and 37 adjacent non-tumor tissues and evaluated its correlation with clinicopathological parameters including estrogen receptor (ER), progesterone receptor (PR) and HER2/neu status. Expression levels of Ubiquitin C (UBC) were used for normalization. Protein expression of AP-1 members was assessed using Western blot analysis in a subset of tumors. We used student’s t-test, one-way ANOVA, logistic regression and Pearson’s correlation coefficient for statistical analyses. We found significant differences in the expression of AP-1 family members between tumor and adjacent non-tumor tissues for all AP-1 family members except Fos B. Fra-1, Fra-2, Jun-B and Jun-D mRNA levels were significantly higher in tumors compared to adjacent non-tumor tissues (p < 0.001), whilst c-Fos and c-Jun mRNA levels were significantly lower in tumors compared with adjacent non-tumor tissues (p < 0.001). In addition, Jun-B overexpression had outstanding discrimination ability to differentiate tumor tissues from adjacent non-tumor tissues as determined by ROC curve analysis. Moreover, Fra-1 was significantly overexpressed in the tumors biochemically classified as ERα negative (p = 0.012) and PR negative (p = 0.037). Interestingly, Fra-1 expression was significantly higher in triple-negative tumors compared with luminal carcinomas (p = 0.01). Expression levels of Fra-1 and Jun-B might be possible biomarkers for prognosis of breast cancer

  11. Targeted disruption of fibrinogen like protein-1 accelerates hepatocellular carcinoma development

    Energy Technology Data Exchange (ETDEWEB)

    Nayeb-Hashemi, Hamed; Desai, Anal; Demchev, Valeriy [Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine. Brigham and Women' s Hospital and Harvard Medical School, Boston, MA 02115 (United States); Bronson, Roderick T. [Department of Microbiology and Immunology, Harvard Medical School, Boston, MA 02115 (United States); Hornick, Jason L. [Department of Pathology, Brigham and Women' s Hospital and Harvard Medical School, Boston, MA 02115 (United States); Cohen, David E. [Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine. Brigham and Women' s Hospital and Harvard Medical School, Boston, MA 02115 (United States); Ukomadu, Chinweike, E-mail: cukomadu@partners.org [Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine. Brigham and Women' s Hospital and Harvard Medical School, Boston, MA 02115 (United States)

    2015-09-18

    Fibrinogen like protein-1 (Fgl1) is a predominantly liver expressed protein that has been implicated as both a hepatoprotectant and a hepatocyte mitogen. Fgl1 expression is decreased in hepatocellular carcinoma (HCC) and its loss correlates with a poorly differentiated phenotype. To better elucidate the role of Fgl1 in hepatocarcinogenesis, we treated mice wild type or null for Fgl1 with diethyl nitrosamine and monitored for incidence of hepatocellular cancer. We find that mice lacking Fgl1 develop HCC at more than twice the rate of wild type mice. We show that hepatocellular cancers from Fgl1 null mice are molecularly distinct from those of the wild type mice. In tumors from Fgl1 null mice there is enhanced activation of Akt and downstream targets of the mammalian target of rapamycin (mTOR). In addition, there is paradoxical up regulation of putative hepatocellular cancer tumor suppressors; tripartite motif-containing protein 35 (Trim35) and tumor necrosis factor super family 10b (Tnfrsf10b). Taken together, these findings suggest that Fgl1 acts as a tumor suppressor in hepatocellular cancer through an Akt dependent mechanism and supports its role as a potential therapeutic target in HCC. - Highlights: • Fgl1 knockout mice (Fgl1KO) are more prone to carcinogen-induced liver cancer compared to wild type (WT) mates. • Tumors from the Fgl1KO are molecularly distinct with enhanced Akt and mTOR activity in comparison with Fgl1WT tumors. • Tumors from the Fgl1KO have enhanced expression of Trim35 and Tnfrsf10b, putative HCC tumor suppressors.

  12. PTIP associated protein 1, PA1, is an independent prognostic factor for lymphnode negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Takashi Takeshita

    Full Text Available Pax transactivation domain interacting protein (PTIP associated protein 1, PA1, was a newly found protein participating in the modulation of transactivity of nuclear receptor super family members such as estrogen receptor (ER, androgen receptor (AR and glucocorticoid receptor (GR. Breast cancer is one of the most life threatening diseases for women and has tight association with estrogen and ER. This study was performed to understand the function of PA1 in breast cancer. The expression of PA1 had been evaluated in a total of 344 primary invasive breast cancer samples and examined the relationship with clinical output, relapse free survival (RFS, breast cancer-specific survival (BCSS. PA1 expression was observed in both nucleus and cytoplasm, however, appeared mainly in nuclear. PA1 nuclear expression was correlated with postmenopausal (P = 0.0097, smaller tumor size (P = 0.0025, negative Ki67 (P = 0.02, positive AR (P = 0.049 and positive ERβ (P = 0.0020. Kaplan-Meier analysis demonstrated PA1 nuclear positive cases seemed to have a longer survival than negative ones for RFS (P = 0.023 but not for BCSS (P = 0.23. In the Cox hazards model, PA1 nuclear protein expression proved to be a significant prognostic univariate parameter for RFS (P = 0.03, but not for BCSS (P = 0.20. In addition, for those patients without lymphnode metastasis PA1 was found to be an independent prognostic factor for RFS (P = 0.025, which was verified by univariate and multivariate analyses. These investigations suggested PA1 expression could be a potential prognostic indicator for RFS in breast cancer.

  13. Interaction of Human Chloride Intracellular Channel Protein 1 (CLIC1) with Lipid Bilayers: A Fluorescence Study.

    Science.gov (United States)

    Hare, Joanna E; Goodchild, Sophia C; Breit, Samuel N; Curmi, Paul M G; Brown, Louise J

    2016-07-12

    Chloride intracellular channel protein 1 (CLIC1) is very unusual as it adopts a soluble glutathione S-transferase-like canonical fold but can also autoinsert into lipid bilayers to form an ion channel. The conversion between these forms involves a large, but reversible, structural rearrangement of the CLIC1 module. The only identified environmental triggers controlling the metamorphic transition of CLIC1 are pH and oxidation. Until now, there have been no high-resolution structural data available for the CLIC1 integral membrane state, and consequently, a limited understanding of how CLIC1 unfolds and refolds across the bilayer to form a membrane protein with ion channel activity exists. Here we show that fluorescence spectroscopy can be used to establish the interaction and position of CLIC1 in a lipid bilayer. Our method employs a fluorescence energy transfer (FRET) approach between CLIC1 and a dansyl-labeled lipid analogue to probe the CLIC1-lipid interface. Under oxidizing conditions, a strong FRET signal between the single tryptophan residue of CLIC1 (Trp35) and the dansyl-lipid analogue was detected. When considering the proportion of CLIC1 interacting with the lipid bilayer, as estimated by fluorescence quenching experiments, the FRET distance between Trp35 and the dansyl moiety on the membrane surface was determined to be ∼15 Å. This FRET-detected interaction provides direct structural evidence that CLIC1 associates with membranes. The results presented support the current model of an oxidation-driven interaction of CLIC1 with lipid bilayers and also propose a membrane anchoring role for Trp35. PMID:27299171

  14. X-ray structure of engineered human Aortic Preferentially Expressed Protein-1 (APEG-1

    Directory of Open Access Journals (Sweden)

    Scheich Christoph

    2005-12-01

    Full Text Available Abstract Background Human Aortic Preferentially Expressed Protein-1 (APEG-1 is a novel specific smooth muscle differentiation marker thought to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs. Results Good quality crystals that were suitable for X-ray crystallographic studies were obtained following the truncation of the 14 N-terminal amino acids of APEG-1, a region predicted to be disordered. The truncated protein (termed ΔAPEG-1 consists of a single immunoglobulin (Ig like domain which includes an Arg-Gly-Asp (RGD adhesion recognition motif. The RGD motif is crucial for the interaction of extracellular proteins and plays a role in cell adhesion. The X-ray structure of ΔAPEG-1 was determined and was refined to sub-atomic resolution (0.96 Å. This is the best resolution for an immunoglobulin domain structure so far. The structure adopts a Greek-key β-sandwich fold and belongs to the I (intermediate set of the immunoglobulin superfamily. The residues lying between the β-sheets form a hydrophobic core. The RGD motif folds into a 310 helix that is involved in the formation of a homodimer in the crystal which is mainly stabilized by salt bridges. Analytical ultracentrifugation studies revealed a moderate dissociation constant of 20 μM at physiological ionic strength, suggesting that APEG-1 dimerisation is only transient in the cell. The binding constant is strongly dependent on ionic strength. Conclusion Our data suggests that the RGD motif might play a role not only in the adhesion of extracellular proteins but also in intracellular protein-protein interactions. However, it remains to be established whether the rather weak dimerisation of APEG-1 involving this motif is physiogically relevant.

  15. Role of two single nucleotide polymorphisms in secreted frizzled related protein 1 and bladder cancer risk.

    Science.gov (United States)

    Rogler, Anja; Hoja, Sabine; Socher, Eileen; Nolte, Elke; Wach, Sven; Wieland, Wolf; Hofstädter, Ferdinand; Goebell, Peter J; Wullich, Bernd; Hartmann, Arndt; Stoehr, Robert

    2013-01-01

    In this study, we determined the genotype distribution of two single nucleotide polymorphisms (SNPs) in secreted frizzled related protein 1 (SFRP1), rs3242 and rs921142, in a Caucasian bladder cancer case-control study. Allelic variants of the SNPs were determined using restriction fragment length polymorphism (RFLP) analysis and partly verified by sequencing analysis. Overall, DNA from 188 consecutive and 215 early-onset bladder cancer patients (≤45 years) as well as from 332 controls was investigated. Potential microRNA binding sites were determined for rs3242, and microRNA expression was analysed in cell lines and tumour specimens. We observed a remarkable distribution difference in rs3242 between bladder cancer patients and healthy controls (p=0.05). Additionally, we found a significant difference in genotype distribution (p=0.032), resulting from the difference of early-onset patients and the control group (p=0.007). The risk allele T showed increased frequency in the early-onset patient group (p=0.002). Genotype-dependent differences of microRNA binding capacity were predicted in SFRP1 mRNA for two microRNAs. Hsa-miR-3646 showed strong expression in cell lines and tumour tissue, whereas hsa-miR-603 exhibited weak expression. The rs921142 SNP showed no significant association with bladder cancer risk. This is the first study to describe an association of the SFRP1 SNP rs3242 and bladder cancer risk as well as the influence of rs3242 on genotype-dependent microRNA capacity on SFRP1 mRNA. The onset of bladder seems to be associated with the increased occurrence of the T-allele in rs3242. PMID:24133576

  16. Proteolipid protein 1 gene mutation in nine patients with Pelizaeus-Merzbacher disease

    Institute of Scientific and Technical Information of China (English)

    WANG Jing-min; WU Ye; WANG Hui-fang; DENG Yan-hua; YANG Yan-ling; QIN Jiong; LI Xin-yi; WU Xi-ru; JIANG Yu-wu

    2008-01-01

    Background Pelizaeus-Merzbacher disease(PMD)is a rare X-linked recessive disorder with svmptoms including nystagmus,impaired motor development,ataxia,and progressive spasticity.The proteolipid protein 1(PLPl)gene is the only pathogenic gene of PMD.Duplication of the PLP1 gene is the most frequent gene defect.accounting for 500%-70%of PMD cases.whereas point mutations in the coding sequence or the splice sites account for 10%-25%of PMD cases.This study aimed to identify PLP1 mutations in nine unrelated Chinese patients(P1-9)with PMD,and 14 subjects from the family of patient 2 were also described.Methods Genomic DNA was extracted from peripheral blood samples.Gene dosage was determined using the multiplex ligation-dependent probe amplification (MLPA).All 7 exons and exon-intron boundanes of the PLP1 gene were amplified and analyzed using direct DNA sequencing.Reaults Of these nine patients,there were four transitional.four classical,and one connatal PMD according to their clinical and radiological presentations.PLP1 duplications were identified in patients 1-7 with PMD.Their mothers were PLP1 duplications carriers as well.Both duplication carders and normal genotypes of PLP1 were identified in the family members of patient 2.A c.51 7C>T(p.P173S)hemizygous missense mutation in exon 4 was found in patient 8 with PMD,and his mother was shown to be a heterozygote of this mutation.Conclusions We identified seven genomic duplications and one missense mutation(p.P173S)of the PLP1 gene in eight Chinese patients with PMD.This is the report about PLP1 mutations in PMD patients from the mainland of China.

  17. Test systems to study the structure and function of uncoupling protein 1: a critical overview

    Directory of Open Access Journals (Sweden)

    Verena eHirschberg

    2011-11-01

    Full Text Available The discovery of active brown adipose tissue (BAT in healthy adult humans has renewed interest in the biology of this organ. BAT is capable of distributing nutrient energy in the form of heat allowing small mammals to efficiently defend their body temperature when acutely exposed to the cold. On the other hand BAT might be a target for the treatment of obesity and related diseases, as its pharmacological activation could allow release of excess energy stored in white adipose tissue depots. Energy dissipation in BAT depends on the activity of uncoupling protein 1 (UCP1, therefore a BAT-based obesity therapy requires a detailed understanding of structure and function of UCP1. Although UCP1 has been in the focus of research since its discovery, central questions concerning its mechanistic function and regulation are not yet resolved. They have been addressed in native mitochondria but also in several test systems, which are generally used to lower inter-experimental variability and to simplify analysis conditions. Different test systems have contributed to our current knowledge about UCP1 but of course all of them have certain limitations. We here provide an overview about research on UCP1 structure and function in test systems. So far, these have nearly exclusively been employed to study rodent and not human UCP1. Considering that the amino acid sequence of mouse and human UCP1 is only 79% identical, it will be essential to test whether the human version has a similarly high catalytic activity, allowing a relevant amount of energy dissipation in human BAT. Besides the issue of comparable mechanistic function a sufficiently high expression level of human UCP1 is a further prerequisite for anti-obesity therapeutic potential. Treatments which induce BAT hyperplasia and UCP1 expression in humans might therefore be equally important to discover as mere activators of the thermogenic process.

  18. Niche-specific requirement for hyphal wall protein 1 in virulence of Candida albicans.

    Directory of Open Access Journals (Sweden)

    Janet F Staab

    Full Text Available Specialized Candida albicans cell surface proteins called adhesins mediate binding of the fungus to host cells. The mammalian transglutaminase (TG substrate and adhesin, Hyphal wall protein 1 (Hwp1, is expressed on the hyphal form of C. albicans where it mediates fungal adhesion to epithelial cells. Hwp1 is also required for biofilm formation and mating thus the protein functions in both fungal-host and self-interactions. Hwp1 is required for full virulence of C. albicans in murine models of disseminated candidiasis and of esophageal candidiasis. Previous studies correlated TG activity on the surface of oral epithelial cells, produced by epithelial TG (TG1, with tight binding of C. albicans via Hwp1 to the host cell surfaces. However, the contribution of other Tgs, specifically tissue TG (TG2, to disseminated candidiasis mediated by Hwp1 was not known. A newly created hwp1 null strain in the wild type SC5314 background was as virulent as the parental strain in C57BL/6 mice, and virulence was retained in C57BL/6 mice deleted for Tgm2 (TG2. Further, the hwp1 null strains displayed modestly reduced virulence in BALB/c mice as did strain DD27-U1, an independently created hwp1Δ/Δ in CAI4 corrected for its ura3Δ defect at the URA3 locus. Hwp1 was still needed to produce wild type biofilms, and persist on murine tongues in an oral model of oropharyngeal candidiasis consistent with previous studies by us and others. Finally, lack of Hwp1 affected the translocation of C. albicans from the mouse intestine into the bloodstream of mice. Together, Hwp1 appears to have a minor role in disseminated candidiasis, independent of tissue TG, but a key function in host- and self-association to the surface of oral mucosa.

  19. Controlled release of recombinant human cementum protein 1 from electrospun multiphasic scaffold for cementum regeneration.

    Science.gov (United States)

    Chen, Xiaofeng; Liu, Yu; Miao, Leiying; Wang, Yangyang; Ren, Shuangshuang; Yang, Xuebin; Hu, Yong; Sun, Weibin

    2016-01-01

    Periodontitis is a major cause for tooth loss, which affects about 15% of the adult population. Cementum regeneration has been the crux of constructing the periodontal complex. Cementum protein 1 (CEMP1) is a cementum-specific protein that can induce cementogenic differentiation. In this study, poly(ethylene glycol) (PEG)-stabilized amorphous calcium phosphate (ACP) nanoparticles were prepared by wet-chemical method and then loaded with recombinant human CEMP1 (rhCEMP1) for controlled release. An electrospun multiphasic scaffold constituted of poly(ε-caprolactone) (PCL), type I collagen (COL), and rhCEMP1/ACP was fabricated. The effects of rhCEMP1/ACP/PCL/COL scaffold on the attachment proliferation, osteogenic, and cementogenic differentiations of human periodontal ligament cells, (PDLCs) were systematically investigated. A critical size defect rat model was introduced to evaluate the effect of tissue regeneration of the scaffolds in vivo. The results showed that PEG-stabilized ACP nanoparticles formed a core-shell structure with sustained release of rhCEMP1 for up to 4 weeks. rhCEMP1/ACP/PCL/COL scaffold could suppress PDLCs proliferation behavior and upregulate the expression of cementoblastic markers including CEMP1 and cementum attachment protein while downregulating osteoblastic markers including osteocalcin and osteopontin when it was cocultured with PDLCs in vitro for 7 days. Histology analysis of cementum after being implanted with the scaffold in rats for 8 weeks showed that there was cementum-like tissue formation but little bone formation. These results indicated the potential of using electrospun multiphasic scaffolds for controlled release of rhCEMP1 for promoting cementum regeneration in reconstruction of the periodontal complex. PMID:27471382

  20. Dengue Virus Nonstructural Protein 1 Induces Vascular Leakage through Macrophage Migration Inhibitory Factor and Autophagy.

    Science.gov (United States)

    Chen, Hong-Ru; Chuang, Yung-Chun; Lin, Yee-Shin; Liu, Hsiao-Sheng; Liu, Ching-Chuan; Perng, Guey-Chuen; Yeh, Trai-Ming

    2016-07-01

    Dengue virus (DENV) is the most common mosquito-borne flavivirus; it can either cause mild dengue fever or the more severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). One of the characteristic features of DHF/DSS is vascular leakage; although DENV nonstructural protein 1 (NS1) has been proved to induce vascular leakage after binding to Toll-like receptor 4, the down-stream mechanism has not yet been fully understood. In the sera of DENV-infected patients, the concentrations of DENV NS1 and inflammatory cytokine macrophage migration inhibitory factor (MIF) are positively correlated with disease severity, but whether DENV NS1 induces vascular leakage through MIF secretion remains unknown. We demonstrated that recombinant NS1 induced vascular leakage and MIF secretion both in human endothelial cell line HMEC-1 and in mice. Furthermore, these phenomena were inhibited in the presence of anti-NS1 antibodies both in vitro and in vivo. DENV NS1 also induced LC3-I to LC3-II conversion and p62 degradation in endothelial cell line, which indicated the formation of autophagy. To clarify whether MIF or autophagy mediated DENV NS1-induced vascular leakage, various inhibitors were applied. The results showed that DENV NS1-induced vascular leakage and VE-cadherin disarray were blocked in the presence of MIF inhibitors, anti-MIF-antibodies or autophagy inhibitors. An Atg5 knockdown clone further confirmed that autophagy formation of endothelial cells was required in NS1-induced vascular leakage. Furthermore, DENV NS1-induced LC3 puncta were also decreased in the presence of MIF inhibitors, indicating that MIF mediated DENV NS1-induced autophagy. Taken together, the results suggest a potential mechanism of DENV-induced vascular leakage and provide possible therapeutic targets against DHF/DSS. PMID:27409803

  1. Insight into temperature dependence of GTPase activity in human guanylate binding protein-1.

    Directory of Open Access Journals (Sweden)

    Anjana Rani

    Full Text Available Interferon-γ induced human guanylate binding protein-1(hGBP1 belongs to a family of dynamin related large GTPases. Unlike all other GTPases, hGBP1 hydrolyzes GTP to a mixture of GDP and GMP with GMP being the major product at 37°C but GDP became significant when the hydrolysis reaction was carried out at 15°C. The hydrolysis reaction in hGBP1 is believed to involve with a number of catalytic steps. To investigate the effect of temperature in the product formation and on the different catalytic complexes of hGBP1, we carried out temperature dependent GTPase assays, mutational analysis, chemical and thermal denaturation studies. The Arrhenius plot for both GDP and GMP interestingly showed nonlinear behaviour, suggesting that the product formation from the GTP-bound enzyme complex is associated with at least more than one step. The negative activation energy for GDP formation and GTPase assay with external GDP together indicate that GDP formation occurs through the reversible dissociation of GDP-bound enzyme dimer to monomer, which further reversibly dissociates to give the product. Denaturation studies of different catalytic complexes show that unlike other complexes the free energy of GDP-bound hGBP1 decreases significantly at lower temperature. GDP formation is found to be dependent on the free energy of the GDP-bound enzyme complex. The decrease in the free energy of this complex at low temperature compared to at high is the reason for higher GDP formation at low temperature. Thermal denaturation studies also suggest that the difference in the free energy of the GTP-bound enzyme dimer compared to its monomer plays a crucial role in the product formation; higher stability favours GMP but lower favours GDP. Thus, this study provides the first thermodynamic insight into the effect of temperature in the product formation of hGBP1.

  2. Controlled release of recombinant human cementum protein 1 from electrospun multiphasic scaffold for cementum regeneration

    Science.gov (United States)

    Chen, Xiaofeng; Liu, Yu; Miao, Leiying; Wang, Yangyang; Ren, Shuangshuang; Yang, Xuebin; Hu, Yong; Sun, Weibin

    2016-01-01

    Periodontitis is a major cause for tooth loss, which affects about 15% of the adult population. Cementum regeneration has been the crux of constructing the periodontal complex. Cementum protein 1 (CEMP1) is a cementum-specific protein that can induce cementogenic differentiation. In this study, poly(ethylene glycol) (PEG)-stabilized amorphous calcium phosphate (ACP) nanoparticles were prepared by wet-chemical method and then loaded with recombinant human CEMP1 (rhCEMP1) for controlled release. An electrospun multiphasic scaffold constituted of poly(ε-caprolactone) (PCL), type I collagen (COL), and rhCEMP1/ACP was fabricated. The effects of rhCEMP1/ACP/PCL/COL scaffold on the attachment proliferation, osteogenic, and cementogenic differentiations of human periodontal ligament cells, (PDLCs) were systematically investigated. A critical size defect rat model was introduced to evaluate the effect of tissue regeneration of the scaffolds in vivo. The results showed that PEG-stabilized ACP nanoparticles formed a core-shell structure with sustained release of rhCEMP1 for up to 4 weeks. rhCEMP1/ACP/PCL/COL scaffold could suppress PDLCs proliferation behavior and upregulate the expression of cementoblastic markers including CEMP1 and cementum attachment protein while downregulating osteoblastic markers including osteocalcin and osteopontin when it was cocultured with PDLCs in vitro for 7 days. Histology analysis of cementum after being implanted with the scaffold in rats for 8 weeks showed that there was cementum-like tissue formation but little bone formation. These results indicated the potential of using electrospun multiphasic scaffolds for controlled release of rhCEMP1 for promoting cementum regeneration in reconstruction of the periodontal complex. PMID:27471382

  3. [Preparation and detection of anti-influenza A virus polymerase basic protein 1 polyclonal antibody].

    Science.gov (United States)

    Qin, Yujie; Zhang, Tinghong; Ye, Xin

    2016-01-01

    Influenza A virus is an enveloped virus that belongs to the Orthomyxoviridae family. It has 8 negative RNA segments that encode 16 viral proteins. The viral polymerase consists of 3 proteins (PB 1, PB2 and PA) which plays an important role in the transcription and replication of the influenza A virus. Polymerase basic protein 1 (PB 1) is a critical member of viral polymerase complex. In order to further study the function of PB1, we need to prepare the PB1 antibody with good quality. Therefore, we amplified PB1 conserved region (nt1648-2265) by PCR and cloned it into pET-30a vector, and transformed into Escherichia coli BL2 1. The expression of His tagged PB 1 protein was induced by IPTG, and His-PB 1 proteins were purified by Ni-NTA resin. For preparation of PB 1 protein antiserum, rabbits were immunized with His-PB 1 fusion protein 3 times. Then the titer of PB 1 polyclonal antibody was measured by indirect ELISA. The antibody was purified by membrane affinity purification and subjected to immunoblotting analysis. Data showed that PB1 antibody can recognize PB 1 protein from WSN virus infected or pCMV FLAG-PB 1 transfected cells. Meanwhile, PB 1 antibody can also recognize specifically other subtype strains of influenza A virus such as H9N2 and H3N2. PB 1 polyclonal antibody we generated will be a useful tool to study the biological function of PB1. PMID:27363203

  4. Structure and function of epididymal protein cysteine-rich secretory protein-1

    Institute of Scientific and Technical Information of China (English)

    Kenneth P. Roberts; Daniel S. Johnston; Michael A. Nolan; Joseph L. Wooters; Nicole C. Waxmonsky; Laura B. Piehl; Kathy M. Ensrud-Bowlin; David W. Hamilton

    2007-01-01

    Cysteine-rich secretory protein-1 (CRISP-1) is a glycoprotein secreted by the epididymal epithelium. It is a member of a large family of proteins characterized by two conserved domains and a set of 16 conserved cysteine residues. In mammals, CRISP-1 inhibits sperm-egg fusion and can suppress sperm capacitation. The molecular mechanism of action of the mammalian CRISP proteins remains unknown, but certain non-mammalian CRISP proteins can block ion channels. In the rat, CRISP-1 comprises two forms referred to as Proteins D and E. Recent work in our laboratory demonstrates that the D form of CRISP-1 associates transiently with the sperm surface, whereas the E form binds tightly. When the spermatozoa are washed, the E form of CRISP-1 persists on the sperm surface after all D form has dissociated. Cross-linking studies demonstrate different protein-protein interaction patterns for D and E, although no binding partners for either protein have yet been identified. Mass spectrometric analyses revealed a potential post-translational modification on the E form that is not present on the D form. This is the only discernable difference between Proteins D and E, and presumably is responsible for the difference in behavior of these two forms of rat CRISP- 1. These studies demonstrate that the more abundant D form interacts with spermatozoa transiently,possibly with a specific receptor on the sperm surface, consistent with a capacitation-suppressing function during sperm transit and storage in the epididymis, and also confirm a tightly bound population of the E form that could act in the female reproductive tract.

  5. Systemic administration of the chemokine macrophage inflammatory protein 1α exacerbates inflammatory bowel disease in a mouse model

    OpenAIRE

    Pender, S L-F; Chance, V; Whiting, C V; Buckley, M; Edwards, M.; Pettipher, R; MacDonald, T T

    2005-01-01

    Introduction: Exacerbations of inflammatory bowel disease are thought to be related to concurrent infections. As infections are associated with elevated local and serum concentrations of chemokines, we have determined whether systemic administration of the CC chemokine macrophage inflammatory protein 1α (MIP-1α) exacerbates colitis in a mouse model.

  6. Plasmodium falciparum erythrocyte membrane protein 1 domain cassettes 8 and 13 are associated with severe malaria in children

    DEFF Research Database (Denmark)

    Lavstsen, Thomas; Turner, Louise; Saguti, Fredy;

    2012-01-01

    The clinical outcome of Plasmodium falciparum infections ranges from asymptomatic parasitemia to severe malaria syndromes associated with high mortality. The virulence of P. falciparum infections is associated with the type of P. falciparum erythrocyte membrane protein 1 (PfEMP1) expressed on the...

  7. Dwarfism and impaired gut development in insulin-like growth factor II mRNA-binding protein 1-deficient mice

    DEFF Research Database (Denmark)

    Hansen, Thomas V O; Hammer, Niels A; Nielsen, Jacob;

    2004-01-01

    Insulin-like growth factor II mRNA-binding protein 1 (IMP1) belongs to a family of RNA-binding proteins implicated in mRNA localization, turnover, and translational control. Mouse IMP1 is expressed during early development, and an increase in expression occurs around embryonic day 12.5 (E12.5). T...

  8. Immunoglobulin G reactivities to rhoptry-associated protein-1 associated with decreased levels of Plasmodium falciparum parasitemia in Tanzanian children

    DEFF Research Database (Denmark)

    Jakobsen, P H; Lemnge, M M; Abu-Zeid, Y A;

    1996-01-01

    In the Muheza region of Tanzania, an area with holoendemic malaria, the proportion of responders with IgG enzyme-linked immunosorbent assay reactivities to recombinant rhoptry-associated protein-1 (rRAP-1) as well as IgG reactivities to a repeat region of the acidic-basic repeat antigen (ABRA) in...

  9. Characterization of the in vitro binding and inhibition kinetics of primary amine oxidase/vascular adhesion protein-1 by glucosamine.

    LENUS (Irish Health Repository)

    Olivieri, Aldo

    2012-04-01

    Primary-amine oxidase (PrAO) catalyzes the oxidative deamination of endogenous and exogenous primary amines and also functions, in some tissues, as an inflammation-inducible endothelial factor, known as vascular adhesion protein-1. VAP-1 mediates the slow rolling and adhesion of lymphocytes to endothelial cells in a number of inflammatory conditions, including inflammation of the synovium.

  10. Down-expression of tumor protein p53-induced nuclear protein 1 in human gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Pei-Hong Jiang; Yoshiharu Motoo; Stéphane Garcia; Juan Lucio Iovanna; Marie-Josèphe Pébusque; Norio Sawabu

    2006-01-01

    AIM: Overexpression of tumor protein p53-induced nuclear protein 1 (TP53INP1) induces G1 cell cycle arrest and increases p53-mediated apoptosis. To clarify the clinical importance of TP53INP1, we analyzed TP53INP1and p53 expression in gastric cancer.METHODS: TP53INP1 and p53 expression were examined using immunohistochemistry in 142 cases of gastric cancer. The apoptosis of gastric cancer cells was analyzed using the TUNEL method. The relationship between the expression of TP53INP1 and clinicopathological factors was statistically analyzed.RESULTS: TP53INP1 was expressed in 98% (139/142cases) of non-cancerous gastric tissues and was downexpressed in 64% (91/142 cases) of gastric cancer lesions from the same patients. TP53INP1 expression was significantly decreased (43.9%) in poorly differentiated adenocarcinoma compared with well or moderately differentiated adenocarcinoma (81.6%).Cancers invading the submucosa or deeper showed lower positively (59.1%) compared with mucosal cancers (85.2%). Decrease or loss of TP53INP1 expression was significantly correlated with lymphatic invasion (54.3%vs 82.0% without lymphatic invasion) and node-positive patients (31.3% vs 68.3% in node-negative patients).P53 was expressed in 68 (47.9%) patients of gastric cancer, whereas it was absent in normal gastric tissues.A significant association was also observed between TP53INP1 status and the level of apoptosis in tumor cells: the apoptotic index in TP53INP1-positive tissues was significantly higher than that in TP53INP1-negative portions. Finally, when survival data were analyzed,loss of TP53INP1 expression had a significant effect in predicting a poor prognosis (P= 0.0006).CONCLUSION: TP53INP1-positive rate decreases with the progression of gastric cancer. TP53INP1 protein negativity is significantly associated with aggressive pathological phenotypes of gastric cancer. TP53INP1is related to the apoptosis of gastric cancer cells. The decreased expression of the TP53INP1 protein may

  11. Cannabinoid receptor-interacting protein 1a modulates CB1 receptor signaling and regulation.

    Science.gov (United States)

    Smith, Tricia H; Blume, Lawrence C; Straiker, Alex; Cox, Jordan O; David, Bethany G; McVoy, Julie R Secor; Sayers, Katherine W; Poklis, Justin L; Abdullah, Rehab A; Egertová, Michaela; Chen, Ching-Kang; Mackie, Ken; Elphick, Maurice R; Howlett, Allyn C; Selley, Dana E

    2015-04-01

    Cannabinoid CB1 receptors (CB1Rs) mediate the presynaptic effects of endocannabinoids in the central nervous system (CNS) and most behavioral effects of exogenous cannabinoids. Cannabinoid receptor-interacting protein 1a (CRIP1a) binds to the CB1R C-terminus and can attenuate constitutive CB1R-mediated inhibition of Ca(2+) channel activity. We now demonstrate cellular colocalization of CRIP1a at neuronal elements in the CNS and show that CRIP1a inhibits both constitutive and agonist-stimulated CB1R-mediated guanine nucleotide-binding regulatory protein (G-protein) activity. Stable overexpression of CRIP1a in human embryonic kidney (HEK)-293 cells stably expressing CB1Rs (CB1-HEK), or in N18TG2 cells endogenously expressing CB1Rs, decreased CB1R-mediated G-protein activation (measured by agonist-stimulated [(35)S]GTPγS (guanylyl-5'-[O-thio]-triphosphate) binding) in both cell lines and attenuated inverse agonism by rimonabant in CB1-HEK cells. Conversely, small-interfering RNA-mediated knockdown of CRIP1a in N18TG2 cells enhanced CB1R-mediated G-protein activation. These effects were not attributable to differences in CB1R expression or endocannabinoid tone because CB1R levels did not differ between cell lines varying in CRIP1a expression, and endocannabinoid levels were undetectable (CB1-HEK) or unchanged (N18TG2) by CRIP1a overexpression. In CB1-HEK cells, 4-hour pretreatment with cannabinoid agonists downregulated CB1Rs and desensitized agonist-stimulated [(35)S]GTPγS binding. CRIP1a overexpression attenuated CB1R downregulation without altering CB1R desensitization. Finally, in cultured autaptic hippocampal neurons, CRIP1a overexpression attenuated both depolarization-induced suppression of excitation and inhibition of excitatory synaptic activity induced by exogenous application of cannabinoid but not by adenosine A1 agonists. These results confirm that CRIP1a inhibits constitutive CB1R activity and demonstrate that CRIP1a can also inhibit agonist

  12. Influenza virus non-structural protein 1 (NS1 disrupts interferon signaling.

    Directory of Open Access Journals (Sweden)

    Danlin Jia

    Full Text Available Type I interferons (IFNs function as the first line of defense against viral infections by modulating cell growth, establishing an antiviral state and influencing the activation of various immune cells. Viruses such as influenza have developed mechanisms to evade this defense mechanism and during infection with influenza A viruses, the non-structural protein 1 (NS1 encoded by the virus genome suppresses induction of IFNs-α/β. Here we show that expression of avian H5N1 NS1 in HeLa cells leads to a block in IFN signaling. H5N1 NS1 reduces IFN-inducible tyrosine phosphorylation of STAT1, STAT2 and STAT3 and inhibits the nuclear translocation of phospho-STAT2 and the formation of IFN-inducible STAT1:1-, STAT1:3- and STAT3:3- DNA complexes. Inhibition of IFN-inducible STAT signaling by NS1 in HeLa cells is, in part, a consequence of NS1-mediated inhibition of expression of the IFN receptor subunit, IFNAR1. In support of this NS1-mediated inhibition, we observed a reduction in expression of ifnar1 in ex vivo human non-tumor lung tissues infected with H5N1 and H1N1 viruses. Moreover, H1N1 and H5N1 virus infection of human monocyte-derived macrophages led to inhibition of both ifnar1 and ifnar2 expression. In addition, NS1 expression induces up-regulation of the JAK/STAT inhibitors, SOCS1 and SOCS3. By contrast, treatment of ex vivo human lung tissues with IFN-α results in the up-regulation of a number of IFN-stimulated genes and inhibits both H5N1 and H1N1 virus replication. The data suggest that NS1 can directly interfere with IFN signaling to enhance viral replication, but that treatment with IFN can nevertheless override these inhibitory effects to block H5N1 and H1N1 virus infections.

  13. Protection against dengue virus infection in mice by administration of antibodies against modified nonstructural protein 1.

    Directory of Open Access Journals (Sweden)

    Shu-Wen Wan

    Full Text Available BACKGROUND: Infection with dengue virus (DENV may cause life-threatening disease with thrombocytopenia and vascular leakage which are related to dysfunction of platelets and endothelial cells. We previously showed that antibodies (Abs against DENV nonstructural protein 1 (NS1 cross-react with human platelets and endothelial cells, leading to functional disturbances. Based on sequence homology analysis, the C-terminal region of DENV NS1 protein contains cross-reactive epitopes. For safety in vaccine development, the cross-reactive epitopes of DENV NS1 protein should be deleted or modified. METHODOLOGY/PRINCIPAL FINDINGS: We tested the protective effects of Abs against full-length DENV NS1, NS1 lacking the C-terminal amino acids (a.a. 271-352 (designated ΔC NS1, and chimeric DJ NS1 consisting of N-terminal DENV NS1 (a.a. 1-270 and C-terminal Japanese encephalitis virus NS1 (a.a. 271-352. The anti-ΔC NS1 and anti-DJ NS1 Abs showed a lower binding activity to endothelial cells and platelets than that of anti-DENV NS1 Abs. Passive immunization with anti-ΔC NS1 and anti-DJ NS1 Abs reduced DENV-induced prolonged mouse tail bleeding time. Treatment with anti-DENV NS1, anti-ΔC NS1 and anti-DJ NS1 Abs reduced local skin hemorrhage, controlled the viral load of DENV infection in vivo, synergized with complement to inhibit viral replication in vitro, as well as abolished DENV-induced macrophage infiltration to the site of skin inoculation. Moreover, active immunization with modified NS1 protein, but not with unmodified DENV NS1 protein, reduced DENV-induced prolonged bleeding time, local skin hemorrhage, and viral load. CONCLUSIONS/SIGNIFICANCE: These results support the idea that modified NS1 proteins may represent an improved strategy for safe and effective vaccine development against DENV infection.

  14. Mammalian Clusterin associated protein 1 is an evolutionarily conserved protein required for ciliogenesis

    Directory of Open Access Journals (Sweden)

    Pasek Raymond C

    2012-11-01

    Full Text Available Abstract Background Clusterin associated protein 1 (CLUAP1 was initially characterized as a protein that interacts with clusterin, and whose gene is frequently upregulated in colon cancer. Although the consequences of these observations remain unclear, research of CLUAP1 homologs in C. elegans and zebrafish indicates that it is needed for cilia assembly and maintenance in these models. To begin evaluating whether Cluap1 has an evolutionarily conserved role in cilia in mammalian systems and to explore the association of Cluap1 with disease pathogenesis and developmental abnormalities, we generated Cluap1 mutant mice. Methods Cluap1 mutant embryos were generated and examined for gross morphological and anatomical defects using light microscopy. Reverse transcription PCR, β-galactosidase staining assays, and immunofluorescence analysis were used to determine the expression of the gene and localization of the protein in vivo and in cultured cell lines. We also used immunofluorescence analysis and qRT-PCR to examine defects in the Sonic hedgehog signaling pathway in mutant embryos. Results Cluap1 mutant embryos die in mid-gestation, indicating that it is necessary for proper development. Mutant phenotypes include a failure of embryonic turning, an enlarged pericardial sac, and defects in neural tube development. Consistent with the diverse phenotypes, Cluap1 is widely expressed. Furthermore, the Cluap1 protein localizes to primary cilia, and mutant embryos were found to lack cilia at embryonic day 9.5. The phenotypes observed in Cluap1 mutant mice are indicative of defects in Sonic hedgehog signaling. This was confirmed by analyzing hedgehog signaling activity in Cluap1 mutants, which revealed that the pathway is repressed. Conclusions These data indicate that the function of Cluap1 is evolutionarily conserved with regard to ciliogenesis. Further, the results implicate mammalian Cluap1 as a key regulator of hedgehog signaling and as an

  15. Hemolysin coregulated protein 1 as a molecular gluing unit for the assembly of nanoparticle hybrid structures.

    Science.gov (United States)

    Pham, Tuan Anh; Schreiber, Andreas; Sturm Née Rosseeva, Elena V; Schiller, Stefan; Cölfen, Helmut

    2016-01-01

    Hybrid nanoparticle (NP) structures containing organic building units such as polymers, peptides, DNA and proteins have great potential in biosensor and electronic applications. The nearly free modification of the polymer chain, the variation of the protein and DNA sequence and the implementation of functional moieties provide a great platform to create inorganic structures of different morphology, resulting in different optical and magnetic properties. Nevertheless, the design and modification of a protein structure with functional groups or sequences for the assembly of biohybrid materials is not trivial. This is mainly due to the sensitivity of its secondary, tertiary and quaternary structure to the changes in the interaction (e.g., hydrophobic, hydrophilic, electrostatic, chemical groups) between the protein subunits and the inorganic material. Here, we use hemolysin coregulated protein 1 (Hcp1) from Pseudomonas aeruginosa as a building and gluing unit for the formation of biohybrid structures by implementing cysteine anchoring points at defined positions on the protein rim (Hcp1_cys3). We successfully apply the Hcp1_cys3 gluing unit for the assembly of often linear, hybrid structures of plasmonic gold (Au NP), magnetite (Fe3O4 NP), and cobalt ferrite nanoparticles (CoFe2O4 NP). Furthermore, the assembly of Au NPs into linear structures using Hcp1_cys3 is investigated by UV-vis spectroscopy, TEM and cryo-TEM. One key parameter for the formation of Au NP assembly is the specific ionic strength in the mixture. The resulting network-like structure of Au NPs is characterized by Raman spectroscopy, showing surface-enhanced Raman scattering (SERS) by a factor of 8·10(4) and a stable secondary structure of the Hcp1_cys3 unit. In order to prove the catalytic performance of the gold hybrid structures, they are used as a catalyst in the reduction reaction of 4-nitrophenol showing similar catalytic activity as the pure Au NPs. To further extend the functionality of the

  16. Controlled release of recombinant human cementum protein 1 from electrospun multiphasic scaffold for cementum regeneration

    Directory of Open Access Journals (Sweden)

    Chen XF

    2016-07-01

    Full Text Available Xiaofeng Chen,1,* Yu Liu,1,* Leiying Miao,1 Yangyang Wang,2 Shuangshuang Ren,1 Xuebin Yang,3 Yong Hu,4 Weibin Sun1 1Department of Periodontology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Materials Science and Engineering, College of Materials Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, People’s Republic of China; 3Biomaterials and Tissue Engineering Group, Leeds Dental Institute, University of Leeds, Leeds, UK; 4Institute of Materials Engineering, National Laboratory of Solid State Micro Structure, College of Engineering and Applied Sciences, Nanjing University, Nanjing, Jiangsu, People’s Republic of China *These authors contributed equally to this work Abstract: Periodontitis is a major cause for tooth loss, which affects about 15% of the adult population. Cementum regeneration has been the crux of constructing the periodontal complex. Cementum protein 1 (CEMP1 is a cementum-specific protein that can induce cementogenic differentiation. In this study, poly(ethylene glycol (PEG-stabilized amorphous calcium phosphate (ACP nanoparticles were prepared by wet-chemical method and then loaded with recombinant human CEMP1 (rhCEMP1 for controlled release. An electrospun multiphasic scaffold constituted of poly(ε-caprolactone (PCL, type I collagen (COL, and rhCEMP1/ACP was fabricated. The effects of rhCEMP1/ACP/PCL/COL scaffold on the attachment proliferation, osteogenic, and cementogenic differentiations of human periodontal ligament cells, (PDLCs were systematically investigated. A critical size defect rat model was introduced to evaluate the effect of tissue regeneration of the scaffolds in vivo. The results showed that PEG-stabilized ACP nanoparticles formed a core-shell structure with sustained release of rhCEMP1 for up to 4 weeks. rhCEMP1/ACP/PCL/COL scaffold could suppress PDLCs proliferation behavior

  17. Multidrug resistance protein 1 localization in lipid raft domains and prostasomes in prostate cancer cell lines

    Directory of Open Access Journals (Sweden)

    Gomà A

    2014-12-01

    Full Text Available Alba Gomà,1,* Roser Mir,1–3,* Fina Martínez-Soler,1,4 Avelina Tortosa,4 August Vidal,5,6 Enric Condom,5,6 Ricardo Pérez–Tomás,6 Pepita Giménez-Bonafé1 1Departament de Ciències Fisiològiques II, Faculty of Medicine, Campus of Health Sciences of Bellvitge, Universitat de Barcelona, IDIBELL, Barcelona, Spain; 2División de Investigación Básica, Instituto Nacional de Cancerología, México DF, Mexico; 3Instituto de Física, Universidad Nacional Autónoma de México (UNAM, México DF, Mexico; 4Department of Basic Nursing, School of Nursing of the Health Campus of Bellvitge, Universitat de Barcelona, 5Department of Pathology, Hospital Universitari de Bellvitge, 6Department of Pathology and Experimental Therapeutics, Universitat de Barcelona, IDIBELL, Barcelona, Spain*These authors contributed equally to this work Background: One of the problems in prostate cancer (CaP treatment is the appearance of the multidrug resistance phenotype, in which ATP-binding cassette transporters such as multidrug resistance protein 1 (MRP1 play a role. Different localizations of the transporter have been reported, some of them related to the chemoresistant phenotype.Aim: This study aimed to compare the localization of MRP1 in three prostate cell lines (normal, androgen-sensitive, and androgen-independent in order to understand its possible role in CaP chemoresistance.Methods: MRP1 and caveolae protein markers were detected using confocal microscopy, performing colocalization techniques. Lipid raft isolation made it possible to detect these proteins by Western blot analysis. Caveolae and prostasomes were identified by electron microscopy.Results: We show that MRP1 is found in lipid raft fractions of tumor cells and that the number of caveolae increases with malignancy acquisition. MRP1 is found not only in the plasma membrane associated with lipid rafts but also in cytoplasmic accumulations colocalizing with the prostasome markers Caveolin-1 and CD59

  18. Unilateral macular edema with central retinal vein occlusion in systemic lupus erythematosus: a case report

    Directory of Open Access Journals (Sweden)

    Noma H

    2013-05-01

    Full Text Available Hidetaka Noma,1 Hiroshi Shimizu,1 Tatsuya Mimura21Department of Ophthalmology, Yachiyo Medical Center, Tokyo Women's Medical University, 2Department of Ophthalmology, Medical Center East, Tokyo Women's Medical University, Tokyo, JapanAbstract: Central retinal vein occlusion (CRVO is frequent in patients with systemic lupus erythematosus (SLE, but the treatment of the macular edema with this disease is extremely difficult. We report a case of cystoid macular edema (CME secondary to unilateral CRVO in a patient with SLE that responded to intravitreous injection of an anti-vascular endothelial growth factor (VEGF agent. A 33-year-old Japanese woman was referred to our department with unilateral impairment of vision. Microperimetry (MP-1 showed a cessation of foveal sensitivity. Fluorescein angiography showed CME without ischaemia of the macular region or peripheral retina (nonischemic CRVO. A diagnosis of CME and unilateral nonischemic CRVO combined with SLE was made and intravitreous anti-VEGF therapy was given. A sample of aqueous humor was harvested at the start of intravitreous injection after obtaining informed consent. Then the levels of VEGF and monocyte chemotactic protein (MCP-1 were measured in the aqueous humor by enzyme-linked immunosorbent assay, revealing that VEGF was 234 pg/mL and MCP-1 was 501 pg/mL. Two weeks later, left eye vision improved to 20/20. Optical coherence tomography (OCT showed considerable amelioration of retinal swelling and CME. MP-1 showed a marked increase of foveal sensitivity. However, she had recurrence of edema 3 months later. After harvesting aqueous humor again, intravitreous injection of an anti-VEGF agent was repeated for CME. The aqueous VEGF and MCP-1 levels were 156 pg/mL and 360 pg/mL, respectively. These findings suggest that inflammation was improved by intravitreous injection of bevacizumab. Intravitreous injection of anti-VEGF agents may be effective for CME due to nonischemic CRVO in SLE patients

  19. Effect of salvianolate on intestinal epithelium tight junction protein zonula occludens protein 1 in cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    Dan-Hong Yang; Zai-Yuan Ye; Yuan-Jun Xie; Xu-Jun He; Wen-Juan Xu; Wei-Ming Zhou

    2012-01-01

    AIM:To study the effect of salvianolate on tight junctions (TJs) and zonula occludens protein 1 (ZO-1) in small intestinal mucosa of cirrhotic rats.METHODS:Cirrhosis was induced using carbon tetrachloride.Rats were randomly divided into the untreated group,low-dose salvianolate (12 mg/kg) treatment group,medium-dose salvianolate (24 mg/kg) treatment group,and high-dose salvianolate (48 mg/kg) treatment group,and were treated for 2 wk.Another 10 healthy rats served as the normal control group.Histological changes in liver tissue samples were observed under a light microscope.We evaluated morphologic indices of ileal mucosa including intestinal villi width and thickness of mucosa and intestinal wall using a pathological image analysis system.Ultrastructural changes in small intestinal mucosa were investigated in the five groups using transmission electron microscopy.The changes in ZO-1 expression,a tight junction protein,were analyzed by immunocytochemistry.The staining index was calculated as the product of the staining intensity score and the proportion of positive cells.RESULTS:In the untreated group,hepatocytes showed a disordered arrangement,fatty degeneration was extensive,swelling was obvious,and disorganized lobules were divided by collagen fibers in hepatic tissue,which were partly improved in the salvianolate treated groups.In the untreated group,abundant lymphocytes infiltrated the fibrous tissue with proliferation of bile ducts,and collagen fibers gradually decreased and damaged hepatic lobules were partly repaired following salvianolate treatment.Compared with the untreated group,no differences in intestinal villi width between the five groups were observed.The villi height as well as mucosa and intestinal wall thickness gradually thickened with salvianolate treatment and were significantly shorter in the untreated group compared with those in the salvianolate treatment groups and normal group (P < 0.01).The number of microvilli decreased and showed

  20. Nicotinamide downregulates gene expression of interleukin-6, interleukin-10, monocyte chemoattractant protein-1, and tumour necrosis factor-α gene expression in HaCaT keratinocytes after ultraviolet B irradiation.

    Science.gov (United States)

    Monfrecola, G; Gaudiello, F; Cirillo, T; Fabbrocini, G; Balato, A; Lembo, S

    2013-03-01

    Ultraviolet (UV) radiation has profound effects on human skin, causing sunburn, inflammation, cellular-tissue injury, cell death, and skin cancer. Most of these effects are mediated by a number of cytokines produced by keratinocytes. In this study we investigated whether nicotinamide (NCT), the amide form of vitamin B3, might have a protective function in reducing the expression of interleukin (IL)-1β, IL-6, IL-8, IL-10, monocyte chemoattractant protein (MCP)-1 and tumour necrosis factor (TNF)-α in UV-irradiated keratinocytes. HaCaT cells were treated with UVB in the presence or absence of NCT, and cytokine mRNA levels were examined by quantitative real-time PCR. NCT significantly downregulated IL-6, IL-10, MCP-1 and TNF-α mRNA expression, whereas it did not exert any significant effect on IL-1β or IL-8 expression. Because of its ability to decrease these cytokine mediators after UV exposure, NCT is a possible therapy to improve or prevent conditions induced or aggravated by UV light.

  1. Purification and sequencing of the active site tryptic peptide from penicillin-binding protein 1b of Escherichia coli

    International Nuclear Information System (INIS)

    This paper reports the sequence of the active site peptide of penicillin-binding protein 1b from Escherichia coli. Purified penicillin-binding protein 1b was labeled with [14C]penicillin G, digested with trypsin, and partially purified by gel filtration. Upon further purification by high-pressure liquid chromatography, two radioactive peaks were observed, and the major peak, representing over 75% of the applied radioactivity, was submitted to amino acid analysis and sequencing. The sequence Ser-Ile-Gly-Ser-Leu-Ala-Lys was obtained. The active site nucleophile was identified by digesting the purified peptide with aminopeptidase M and separating the radioactive products on high-pressure liquid chromatography. Amino acid analysis confirmed that the serine residue in the middle of the sequence was covalently bonded to the [14C]penicilloyl moiety. A comparison of this sequence to active site sequences of other penicillin-binding proteins and beta-lactamases is presented

  2. G protein coupled receptor kinase 2 interacting protein 1 (GIT1) is a novel regulator of mitochondrial biogenesis in heart

    OpenAIRE

    Pang, Jinjiang; Xu, Xiangbin; Getman, Michael R.; Shi, Xi; Belmonte, Stephen L.; Michaloski, Heidi; Mohan, Amy; Blaxall, Burns C.; Berk, Bradford C.

    2011-01-01

    G-protein-coupled receptor (GPCR)-kinase interacting protein-1 (GIT1) is a multi-function scaffold protein. However, little is known about its physiological role in the heart. Here we sought to identify the cardiac function of GIT1. Global GIT1 knockout (KO) mice were generated and exhibited significant cardiac hypertrophy that progressed to heart failure. Electron microscopy revealed that the hearts of GIT1 KO mice demonstrated significant morphological abnormities in mitochondria, including...

  3. Impaired Angiogenesis during Fracture Healing in GPCR Kinase 2 Interacting Protein-1 (GIT1) Knock Out Mice

    OpenAIRE

    Guoyong Yin; Tzong-Jen Sheu; Prashanthi Menon; Jinjiang Pang; Hsin-Chiu Ho; Shanshan Shi; Chao Xie; Elaine Smolock; Chen Yan; Zuscik, Michael J.; Berk, Bradford C.

    2014-01-01

    G protein coupled receptor kinase 2 (GRK2) interacting protein-1 (GIT1), is a scaffold protein that plays an important role in angiogenesis and osteoclast activity. We have previously demonstrated that GIT1 knockout (GIT1 KO) mice have impaired angiogenesis and dysregulated osteoclast podosome formation leading to a reduction in the bone resorbing ability of these cells. Since both angiogenesis and osteoclast-mediated bone remodeling are involved in the fracture healing process, we hypothesiz...

  4. Evolutionary analysis of circumsporozoite surface protein and merozoite surface protein-1 (CSP and MSP-1) sequences of malaria parasites

    OpenAIRE

    Tripathi, Vijay; Gupta, Dwijendra

    2011-01-01

    Malaria, one of the world's most common diseases, is caused by the intracellular protozoan parasite known as Plasmodium. In this study, we have determined the evolutionary relationship of two single-copy proteins, circumsporozoite protein (CSP) and merozoite surface protein-1 (MSP-1), among Plasmodium species using various bioinformatics tools and softwares. These two proteins are major blood stage antigens of Plasmodium species. This study demonstrates that the circumsporozoite protein of Pl...

  5. Inhibition of multidrug resistance protein 1 (MRP1) improves chemotherapy drug response in primary and recurrent glioblastoma multiforme

    OpenAIRE

    Tivnan, Amanda; Zakaria, Zaitun; O'Leary, Caitrín; Kögel, Donat; Pokorny, Jenny L.; Sarkaria, Jann N.; Prehn, Jochen H M

    2015-01-01

    Glioblastoma multiforme (GBM) is a highly aggressive brain cancer with extremely poor prognostic outcome despite intensive treatment. All chemotherapeutic agents currently used have no greater than 30–40% response rate, many fall into the range of 10–20%, with delivery across the blood brain barrier (BBB) or chemoresistance contributing to the extremely poor outcomes despite treatment. Increased expression of the multidrug resistance protein 1(MRP1) in high grade glioma, and it's role in BBB ...

  6. Inhibition of Multidrug resistance protein 1 (MRP1) improves chemotherapy drug response in primary and recurrent glioblastoma multiforme

    OpenAIRE

    Amanda eTivnan; Zaitun eZakaria; Caitrin eO'Leary; Donat eKogel; Pokorny, Jenny L.; Sarkaria, Jann N.; Prehn, Jochen H M

    2015-01-01

    Glioblastoma multiforme (GBM) is a highly aggressive brain cancer with extremely poor prognostic outcome despite intensive treatment. All chemotherapeutic agents currently used have no greater than 30-40% response rate, many fall into the range of 10-20%, with delivery across the blood brain barrier (BBB) or chemoresistance contributing to the extremely poor outcomes despite treatment. Increased expression of the multidrug resistance protein 1(MRP1) in high grade glioma, and it’s role in BB...

  7. Expression of the domain cassette 8 Plasmodium falciparum erythrocyte membrane protein 1 is associated with cerebral malaria in Benin

    DEFF Research Database (Denmark)

    Bertin, Gwladys I; Lavstsen, Thomas; Guillonneau, François;

    2013-01-01

    Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP-1) is a highly polymorphic adherence receptor expressed on the surface of infected erythrocytes. Based on sequence homology PfEMP-1 variants have been grouped into three major groups A-C, the highly conserved VAR2CSA variants, and semi......-conserved types defined by tandem runs of specific domains ("domain cassettes" (DC)). The PfEMP-1 type expressed determines the adherence phenotype, and is associated with clinical outcome of infection....

  8. Nitric Oxide-associated Protein 1 (NOA1) Is Necessary for Oxygen-dependent Regulation of Mitochondrial Respiratory Complexes*

    OpenAIRE

    Heidler, Juliana; Al-Furoukh, Natalie; Kukat, Christian; Salwig, Isabelle; Ingelmann, Marie-Elisabeth; Seibel, Peter; Krüger, Marcus; Holtz, Jürgen; Wittig, Ilka; Braun, Thomas; Szibor, Marten

    2011-01-01

    In eukaryotic cells, maintenance of cellular ATP stores depends mainly on mitochondrial oxidative phosphorylation (OXPHOS), which in turn requires sufficient cellular oxygenation. The crucial role of proper oxygenation for cellular viability is reflected by involvement of several mechanisms, which sense hypoxia and regulate activities of respiratory complexes according to available oxygen concentrations. Here, we focus on mouse nitric oxide-associated protein 1 (mNOA1), which has been identif...

  9. Local cytokine changes in complex regional pain syndrome type I (CRPS I) resolve after 6 months.

    Science.gov (United States)

    Lenz, Melanie; Uçeyler, Nurcan; Frettlöh, Jule; Höffken, Oliver; Krumova, Elena K; Lissek, Silke; Reinersmann, Annika; Sommer, Claudia; Stude, Philipp; Waaga-Gasser, Ana M; Tegenthoff, Martin; Maier, Christoph

    2013-10-01

    There is evidence that inflammatory processes are involved in at least the early phase of complex regional pain syndrome (CRPS). We compared a panel of pro- and antiinflammatory cytokines in skin blister fluids and serum from patients with CRPS and patients with upper-limb pain of other origin (non-CRPS) in the early stage (< 1 year) and after 6 months of pain treatment. Blister fluid was collected from the affected and contralateral nonaffected side. We used a multiplex-10 bead array cytokine assay and Luminex technology to measure protein concentrations of the cytokines interleukin-1 receptor antagonist (IL-1RA), IL-2, IL-6, IL-8, IL-10, IL-12p40, and tumor necrosis factor-alpha (TNF-α) and the chemokines eotaxin, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1β (MIP-1β). We found bilaterally increased proinflammatory TNF-α and MIP-1β and decreased antiinflammatory IL-1RA protein levels in CRPS patients compared to non-CRPS patients. Neither group showed side differences. After 6 months under analgesic treatment, protein levels of all measured cytokines in CRPS patients, except for IL-6, significantly changed bilaterally to the level of non-CRPS patients. These changes were not related to treatment outcome. In serum, only IL-8, TNF-α, eotaxin, MCP-1, and MIP-1β were detectable without intergroup differences. Blister fluid of CRPS patients showed a bilateral proinflammatory cytokine profile. This profile seems to be relevant only at the early stage of CRPS. Almost all measured cytokine levels were comparable to those of non-CRPS patients after 6 months of analgesic treatment and were not related to treatment outcome.

  10. Changes in circulating level of IGF-I and IGF-binding protein-1 from the first to second trimester as predictors of preeclampsia

    DEFF Research Database (Denmark)

    Vatten, Lars J; Nilsen, Tom I L; Juul, Anders;

    2008-01-01

    To assess whether circulating IGF-I and IGF-binding protein-1 (IGFBP-1) in the first and second trimester are associated with subsequent risk of preterm and term preeclampsia.......To assess whether circulating IGF-I and IGF-binding protein-1 (IGFBP-1) in the first and second trimester are associated with subsequent risk of preterm and term preeclampsia....

  11. Specific T-cell recognition of the merozoite proteins rhoptry-associated protein 1 and erythrocyte-binding antigen 1 of Plasmodium falciparum

    DEFF Research Database (Denmark)

    Jakobsen, P H; Hviid, L; Theander, T G;

    1993-01-01

    The merozoite proteins merozoite surface protein 1 (MSP-1) and rhoptry-associated protein 1 (RAP-1) and synthetic peptides containing sequences of MSP-1, RAP-1, and erythrocyte-binding antigen 1, induced in vitro proliferative responses of lymphocytes collected from Ghanaian blood donors living i...

  12. Nuclear multidrug-resistance related protein 1 contributes to multidrug-resistance of mucoepidermoid carcinoma mainly via regulating multidrug-resistance protein 1: a human mucoepidermoid carcinoma cells model and Spearman's rank correlation analysis.

    Directory of Open Access Journals (Sweden)

    Bolei Cai

    Full Text Available BACKGROUND: Multidrug resistance-related protein 1 (MRP1/ABCC1 and multidrug resistance protein 1 (MDR1/P-glycoprotein/ABCB1 are both membrane-bound drug transporters. In contrast to MDR1, MRP1 also transports glutathione (GSH and drugs conjugated to GSH. Due to its extraordinary transport properties, MRP1/ABCC1 contributes to several physiological functions and pathophysiological incidents. We previously found that nuclear translocation of MRP1 contributes to multidrug-resistance (MDR of mucoepidermoid carcinoma (MEC. The present study investigated how MRP1 contributes to MDR in the nuclei of MEC cells. METHODS: Western blot and RT-PCR was carried out to investigate the change of multidrug-resistance protein 1 (MDR1 in MC3/5FU cells after MRP1 was downregulated through RNA interference (RNAi. Immunohistochemistry (IHC staining of 127 cases of MEC tissues was scored with the expression index (EI. The EI of MDR1 and MRP1 (or nuclear MRP1 was analyzed with Spearman's rank correlation analysis. Using multiple tumor tissue assays, the location of MRP1 in other tissues was checked by HIC. Luciferase reporter assays of MDR1 promoter was carried out to check the connection between MRP1 and MDR1 promoter. RESULTS: MRP1 downregulation led to a decreased MDR1 expression in MC3/5FU cells which was caused by decreased activity of MDR1 promoter. IHC study of 127 cases of MEC tissues demonstrated a strong positive correlation between nuclear MRP1 expression and MDR1 expression. Furthermore, IHC study of multiple tumor tissue array sections showed that although nuclear MRP1 widely existed in MEC tissues, it was not found in normal tissues or other tumor tissues. CONCLUSIONS: Our findings indicate that nuclear MRP1 contributes to MDR mainly through regulating MDR1 expression in MEC. And the unique location of MRP1 made it an available target in identifying MEC from other tumors.

  13. 4-hydroxy-2, 3-nonenal activates activator protein-1 and mitogen-activated protein kinases in rat pancreatic stellate cells

    Institute of Scientific and Technical Information of China (English)

    Kazuhiro Kikuta; Atsushi Masamune; Masahiro Satoh; Noriaki Suzuki; Tooru Shimosegawa

    2004-01-01

    AIM: Activated pancreatic stellate cells (PSCs) are implicated in the pathogenesis of pancreatic inflammation and fibrosis,where oxidative stress is thought to play a key role. 4-hydroxy2,3-nonenal (HNE) is generated endogenously during the process of lipid peroxidation, and has been accepted as a mediator of oxidative stress. The aim of this study was to clarify the effects of HNE on the activation of signal transduction pathways and cellular functions in PSCs.METHODS: PSCs were isolated from the pancreas of male Wistar rats after perfusion with collagenase P, and used in their culture-activated, myofibroblast-like phenotype unless otherwise stated. PSCs were treated with physiologically relevant and non-cytotoxic concentrations (up to 5 μmol/L)of HNE. Activation of transcription factors was examined by electrophoretic mobility shift assay and luciferase assay.Activation of mitogen-activated protein (MAP) kinases was assessed by Western blotting using anti-phosphospecific antibodies. Cell proliferation was assessed by measuring the incorporation of 5-bromo-2'-deoxyuridine. Production of type Ⅰ collagen and monocyte chemoattractant protein-1was determined by enzyme-linked immunosorbent assay.The effect of HNE on the transformation of freshly isolated PSCs in culture was also assessed.RESULTS: HNE activated activator protein-1, but not nuclear factor κB. In addition, HNE activated three classes of MAP kinases: extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 MAP kinase. HNE increased type Ⅰ collagen production through the activation of p38 MAP kinase and c-Jun N-terminal kinase. HNE did not alter the proliferation,or monocyte chemoattractant protein-1 production. HNE did not initiate the transformation of freshly isolated PSCs to myofibroblast-like phenotype.CONCLUSION: Specific activation of these signal transduction pathways and altered cell functions such as collagen production by HNE may play a role in the pathogenesis of pancreatic

  14. Sequence analysis of the Epstein-Barr virus (EBV) latent membrane protein-1 gene and promoter region

    DEFF Research Database (Denmark)

    Sandvej, K; Gratama, J W; Munch, M;

    1997-01-01

    wild-type virus isolates, we sequenced the LMP-1 promoter and gene in EBV from lymphoblastoid cell lines from healthy carriers and patients without EBV-associated disease. Sequence changes were often present, and defined at least four main groups of viral isolates, which we designate Groups A through D......Sequence variations in the Epstein-Barr virus (EBV) encoded latent membrane protein-1 (LMP-1) gene have been described in a Chinese nasopharyngeal carcinoma-derived isolate (CAO), and in viral isolates from various EBV-associated tumors. It has been suggested that these genetic changes, which...

  15. Akt kinase-interacting protein1, a novel therapeutic target for lung cancer with EGFR-activating and gatekeeper mutations

    OpenAIRE

    Yamada, Tadaaki; Takeuchi, Shinji; Fujita, Naoya; Nakamura, Akito; Wang, Wei; Li, Qi; Oda, Makoto; Mitsudomi, Tetsuya; Yatabe, Yasushi; Sekido, Yoshitaka; Yoshida, Junji; Higashiyama, Masahiko; Noguchi, Masayuki; Uehara, Hisanori; Nishioka, Yasuhiko

    2013-01-01

    Despite initial dramatic response, epidermal growth factor receptor (EGFR) mutant lung cancer patients always acquire resistance to EGFR-tyrosine kinase inhibitors (TKIs). Gatekeeper T790M mutation in EGFR is the most prevalent genetic alteration underlying acquired resistance to EGFR-TKI, and EGFR mutant lung cancer cells are reported to be addictive to EGFR/Akt signaling even after acquired T790M mutation. Here, we focused on Akt kinase-interacting protein1 (Aki1), a scaffold protein of PI3...

  16. Epigenetic analyses of the insulin-like growth factor binding protein 1 gene in type 1 diabetes and diabetic nephropathy

    OpenAIRE

    Gu, Tianwei; Falhammar, Henrik; Gu, Harvest F.; Brismar, Kerstin

    2014-01-01

    Background Clinical observations have demonstrated that high levels of circulating insulin-like growth factor binding protein-1 (IGFBP-1) are associated with type 1 diabetes (T1D), whereas low serum IGFBP-1 levels are associated with the risk of type 2 diabetes (T2D). Recently, we reported that increased DNA methylation levels in the IGFBP1 gene were associated with T2D. In the present study, we evaluated the epigenetic changes of IGFBP1 in T1D and diabetic nephropathy (DN). Results In total,...

  17. Regulation of insulin-like growth factor binding protein-1 (IGFBP-1) and implications in catabolic conditions

    OpenAIRE

    Lindgren, Björn

    1997-01-01

    This thesis has studied the regulation of IGFBP-1 (insulin-like growth factor binding protein 1), which is one factor regulating the bioavailability of IGF-I with special interest how IGFBP-1 is regulated in vitro and in humans, especially in diabetes and catabolic conditions. The IGFBP-1 cDNA was cloned and used for studies in human hepatoma cells, HepG2, which showed that both insulin and IGF-I could decrease IGFBP-1 in the cell conditioned medium. IGF-I inhibited also IGF...

  18. Unusual Presentation of Pelizaeus-Merzbacher Disease: Female Patient with Deletion of the Proteolipid Protein 1 Gene

    Directory of Open Access Journals (Sweden)

    Teva Brender

    2015-01-01

    Full Text Available Pelizaeus-Merzbacher disease (PMD is neurodegenerative leukodystrophy caused by dysfunction of the proteolipid protein 1 (PLP1 gene on Xq22, which codes for an essential myelin protein. As an X-linked condition, PMD primarily affects males; however there have been a small number of affected females reported in the medical literature with a variety of different mutations in this gene. No affected females to date have a deletion like our patient. In addition to this, our patient has skewed X chromosome inactivation which adds to her presentation as her unaffected mother also carries the mutation.

  19. Low expression of nucleus accumbens-associated protein 1 predicts poor prognosis for patients with pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Nishi, Takeshi; Maruyama, Riruke; Urano, Takeshi; Nakayama, Naomi; Kawabata, Yasunari; Yano, Seiji; Yoshida, Manabu; Nakayama, Kentaro; Miyazaki, Kohji; Takenaga, Keizo; Tanaka, Tsuneo; Tajima, Yoshitsugu

    2012-12-01

    Nucleus accumbens-associated protein 1 (NAC1) is overexpressed in various carcinomas including ovarian, cervical, breast, and pancreatic carcinomas. High expression of NAC1 is considered to have adverse effects on prognosis through negative regulation of growth arrest and DNA-damage-inducible 45-γ interacting protein 1 (GADD45GIP1) in ovarian and cervical carcinomas. In the present study, the expression of NAC1 in pancreatic ductal adenocarcinoma (PDA) was measured using immunohistochemistry and computer-assisted image analysis in order to investigate its correlation with various clinicopathological parameters and prognosis. Patients with low-NAC1 PDA had worse overall survival (P = 0.0010) and a shorter disease-free survival (P = 0.0036) than patients with high-NAC1 PDA. This was a clinical effect opposite to that reported in ovarian and cervical carcinomas. Furthermore, knockdown of NAC1 in pancreatic carcinoma cell lines did not increase expression of the GADD45GIP1 protein. These results indicate that the gene(s) regulated by NAC1 vary depending on the types of carcinoma or originating tissue, and that low expression of NAC1 predicts poor prognosis for patients with PDA.

  20. Antibody reactivity to conserved linear epitopes of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1)

    DEFF Research Database (Denmark)

    Staalsø, T; Khalil, E A; Elhassan, I M;

    1998-01-01

    The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family of protein antigens are involved in adhesion of P. falciparum infected erythrocytes to the capillary endothelium of the host. Antibodies to variable regions of these proteins, measured by agglutination, correlates with clini......The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family of protein antigens are involved in adhesion of P. falciparum infected erythrocytes to the capillary endothelium of the host. Antibodies to variable regions of these proteins, measured by agglutination, correlates...... synthetic peptides derived from conserved regions of PfEMP1. The antibody responses to these peptides increased with age and were higher in individuals with asymptomatic P. falciparum infection compared to individuals presenting with fever attributable to falciparum malaria. This indicates that antibodies...... recognising the conserved regions of PfEMP1 arise upon exposure to the parasite, and that these may be involved in the development of protection against malaria. Antibodies to the Pfalhesin peptide of the human aniontransporter, band3, were measured by the same method. The magnitude of this antibody response...