title: Interleukin-13 inhibits cytokines synthesis by blocking nuclear factor-κB and c-Jun N-terminal kinase in human mesangial cells.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing 210008, Jiangsu Province, China ; Institute of Pediatrics, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Zhu
authors.forename: Aihua
authors.initials: A
authors.lastname: Zhang
authors.forename: Songming
authors.initials: S
authors.lastname: Huang
authors.forename: Guixia
authors.initials: G
authors.lastname: Ding
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Pan
authors.forename: Ronghua
authors.initials: R
authors.lastname: Chen
keywords: inflammation; interleukin-13; mesangial cells
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