Role of interleukin 17 in TGF-β signaling-mediated renal interstitial fibrosis

Background: Several studies suggest IL-17 is involved in the pathogenesis of organ fibrosis. The exact role of IL-17 in renal interstitial fibrosis has not been fully elucidated. Methods: We compared the histopathology of renal fibrosis as well as profibrotic TGP-beta signaling in wild-type (WT) and IL-17 knockout (IL-17(-/-)) mice using UUO as the disease model. To find out the possible mechanisms involved in the exacerbated renal fibrosis happened to IL-17 (-)(-/)mice, we analyzed the pattern of ECM synthesis by different fibroblasts cultured with IL-17 and associated signaling mediators. Results: On day3 and day7, IL-17 (-/-)mice developed more severe renal fibrosis compared with WT mice. IL-17 had an inhibitory factor in TGF-beta-induced renal fibroblast activation and ECM synthesis, and sequentially in renal interstitial fibrosis, via down-regulation of Smad-independent pathway (p38MAPK and AKT phosphorylations). Conclusion : IL-17 acts an inhibitory factor in TOP-II-induced renal fibroblast activation and ECM synthesis, and sequentially in renal interstitial fibrosis, via down-regulation of Smad-independent pathway (p38MAPK and AKT phosphorylations). Clarifying the novel regulatory mechanisms of fibrosis by the cytokine IL-17 may lead to a new therapeutic approach for progressive renal disease and fibrosis