Interleukin-13 inhibits cytokines synthesis by blocking nuclear factor-κB and c-Jun N-terminal kinase in human mesangial cells
Chunhua Zhu
Aihua Zhang
Songming Huang
Guixia Ding
Xiaoqin Pan
Ronghua Chen
摘要：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 activator 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.Lipopolysacchorides(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.
机标关键词：synthesishuman mesangial cellsproinflammatory cytokinesIL-13molecular mechanismLPSAP-1processes
分类号：R3(基础医学)
资助基金：the Jiangsu Key Medical Talent Foundation(RC2007015 to Aihua Zhang)
论文发表日期：2010-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
英文信息