IL-17 Promotes HSP47 Expression and Intestinal Fibrosis in Crohn's Disease

Abstract

investigate the role of IL-17 in HSP47 expression and the potential for IL-17 as a new therapeutic target for intestinal fibrosis in CD. Methods: In Vivo study, serum levels of HSP47 in CD, UC and normal subjects were measured by enzyme-linked immunosorbent assay (ELISA). Localization of HSP47 positive cells in the intestine were evaluated by immunohistochemistry (IHC) using intestinal surgical specimens of patients with CD and UC. Gene expressions of HSP47, TGF-β-1, IL-13, HSP70 and IL-17 in the intestinal tissues were examined by quantitative real-time PCR (qRT-PCR). In Vitro study, gene expression of HSP47 in NIH3T3 cells after stimulation with TGF-β-1 or IL-17 was determined by qRT-PCR. Results: (1) Serum levels of HSP47 in patients with CD were significantly higher than in patients with UC and normal subjects. (2) IHC study revealed that HSP47 positive cells were mainly observed in mesenchymal site, submucosa and fibrostenotic site, and that the number of HSP47 positive cells were greater in the intestinal tissues of patients with CD than those with UC. (3) Gene expressions of HSP47, TGF-β-1 and IL-17 were significantly higher in the intestinal tissues of patients with CD than those with UC, while there were no significant differences of HSP70 and IL-13 gene expressions in the intestinal tissues between patients with CD and UC. (4) Gene expression of HSP47 in NIH3T3 cells were up-regulated by IL-17 stimulation as well as TGF-β-1. In addition, p38MAPK inhibitor suppressed HSP47 gene expression in NIH3T3 cells stimulated with IL-17. Conclusion: Our data suggest that IL-17 might be involved in intestinal fibrosis of CD by up-regulation of HSP47 expression in intestinal fibroblasts through p38MAPK pathway. IL-17 could be a new therapeutic target for not only intestinal inflammation but also intestinal fibrosis in CD.