TY - JOUR T1 - Involvement of interleukin-17A-induced expression of heat shock protein 47 in intestinal fibrosis in Crohn's disease JF - Gut JO - Gut SP - 1902 LP - 1912 DO - 10.1136/gutjnl-2013-305632 VL - 63 IS - 12 AU - Yusuke Honzawa AU - Hiroshi Nakase AU - Masahiro Shiokawa AU - Takuya Yoshino AU - Hirotsugu Imaeda AU - Minoru Matsuura AU - Yuzo Kodama AU - Hiroki Ikeuchi AU - Akira Andoh AU - Yoshiharu Sakai AU - Kazuhiro Nagata AU - Tsutomu Chiba Y1 - 2014/12/01 UR - http://gut.bmj.com/content/63/12/1902.abstract N2 - Objective Intestinal fibrosis is a clinically important issue in Crohn's disease (CD). Heat shock protein (HSP) 47 is a collagen-specific molecular chaperone involved in fibrotic diseases. The molecular mechanisms of HSP47 induction in intestinal fibrosis related to CD, however, remain unclear. Here we investigated the role of interleukin (IL)-17A-induced HSP47 expression in intestinal fibrosis in CD. Design Expressions of HSP47 and IL-17A in the intestinal tissues of patients with IBD were determined. HSP47 and collagen I expressions were assessed in intestinal subepithelial myofibroblasts (ISEMFs) isolated from patients with IBD and CCD-18Co cells treated with IL-17A. We examined the role of HSP47 in IL-17A-induced collagen I expression by administration of short hairpin RNA (shRNA) to HSP47 and investigated signalling pathways of IL-17A-induced HSP47 expression using specific inhibitors in CCD-18Co cells. Results Gene expressions of HSP47 and IL-17A were significantly elevated in the intestinal tissues of patients with active CD. Immunohistochemistry revealed HSP47 was expressed in α-smooth muscle actin (α-SMA)-positive cells and the number of HSP47-positive cells was significantly increased in the intestinal tissues of patients with active CD. IL-17A enhanced HSP47 and collagen I expressions in ISEMFs and CCD-18Co cells. Knockdown of HSP47 in these cells resulted in the inhibition of IL-17A-induced collagen I expression, and analysis of IL-17A signalling pathways revealed the involvement of c-Jun N-terminal kinase in IL-17A-induced HSP47 expression. Conclusions IL-17A-induced HSP47 expression is involved in collagen I expression in ISEMFs, which might contribute to intestinal fibrosis in CD. ER -