Interleukin-13 inhibits cytokines synthesis by blocking nuclear factor-κB and c-Jun N-terminal kinase in human mesangial cells

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.