Objective:Monocytes/macrophages,proinflammatory cytokines and chemokines are important in the pathogenesis of glomerulonephritis.Interleukin(IL)-13 has been shown to exert potent anti-inflammatory properties. This stu...Objective:Monocytes/macrophages,proinflammatory cytokines and chemokines are important in the pathogenesis of glomerulonephritis.Interleukin(IL)-13 has been shown to exert potent anti-inflammatory properties. This study was designed to investigate the effect of IL-13 on the expression of proinflammatory cytokines,chemokines and profibrogenic cytokines and the involved molecular mechanism in cultured human mesangial cells (HMCs).Methods:The expressions of proinflammatory cytokines,chemokines and profibrogenic cytokines were determined by ribonuclease protection assay(RPA).Activity of nuclear factor-kappa B(NF-κB)and activa- tor protein-1(AP-1)was examined by electrophoretic mobility shift assay(EMSA).NF-κB subunit p65 nuclear transportation and c-Jun N-terminal kinase(JNK)activity were assayed by immunoblot.Results:Recombinant IL-13 inhibited tumor necrosis factor-α(TNF-α),IL-1α,IL-1β,monocyte chemoattractant protein-1(MCP-1), IL-8,and transforming growth factor-β1(TGF-β1)mRNA expressions in a dose-dependent manner.Lipopoly-sacchorides(LPS)dramatically increased NF-κB DNA binding activity of HMCs,which was inhibited by IL-13 in a dose-dependent manner.LPS-activated NF-κB contained p50 and p65 dimers,but not c-Rel subunit.IL-13 blocked LPS-induced NF-κB subunit p65.LPS stimulated JNK/AP-1 activation,which was inhibited by IL-13 in a dose-dependent manner.Conclusion:IL-13 inhibits proinflammatory cytokines,chemokines,and profibrogenic cytokines synthesis by blocking NF-κB and JNK/AP-1 activation.These observations point to the importance of IL-13 in the modulation of inflammatory processes in the renal glomerulus.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.30872803 to Aihua Zhang,No.30772365 to Songming Huang)the Jiangsu Key Medical Talent Foundation(No.RC2007015 to Aihua Zhangthe Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry of China
文摘Objective:Monocytes/macrophages,proinflammatory cytokines and chemokines are important in the pathogenesis of glomerulonephritis.Interleukin(IL)-13 has been shown to exert potent anti-inflammatory properties. This study was designed to investigate the effect of IL-13 on the expression of proinflammatory cytokines,chemokines and profibrogenic cytokines and the involved molecular mechanism in cultured human mesangial cells (HMCs).Methods:The expressions of proinflammatory cytokines,chemokines and profibrogenic cytokines were determined by ribonuclease protection assay(RPA).Activity of nuclear factor-kappa B(NF-κB)and activa- tor protein-1(AP-1)was examined by electrophoretic mobility shift assay(EMSA).NF-κB subunit p65 nuclear transportation and c-Jun N-terminal kinase(JNK)activity were assayed by immunoblot.Results:Recombinant IL-13 inhibited tumor necrosis factor-α(TNF-α),IL-1α,IL-1β,monocyte chemoattractant protein-1(MCP-1), IL-8,and transforming growth factor-β1(TGF-β1)mRNA expressions in a dose-dependent manner.Lipopoly-sacchorides(LPS)dramatically increased NF-κB DNA binding activity of HMCs,which was inhibited by IL-13 in a dose-dependent manner.LPS-activated NF-κB contained p50 and p65 dimers,but not c-Rel subunit.IL-13 blocked LPS-induced NF-κB subunit p65.LPS stimulated JNK/AP-1 activation,which was inhibited by IL-13 in a dose-dependent manner.Conclusion:IL-13 inhibits proinflammatory cytokines,chemokines,and profibrogenic cytokines synthesis by blocking NF-κB and JNK/AP-1 activation.These observations point to the importance of IL-13 in the modulation of inflammatory processes in the renal glomerulus.
