DOP012. Overexpression of Suppressor of Cytokine Signaling-3 reduces the role of IL22 in mucosal healing and defense
A.T. Xu, Y. Li, Z.H. Ran, J. Shen, X.T. Xu, M.M. Zhu, Y.Q. Qiao, Z.H. Dai, T.R. Wang, Q. Zheng, D. Zhao, School of Medicine, Shanghai Jiao-Tong University, Department of Gastroenterology, Renji hospital, Shanghai, China
Our previous studies shows that SOCS3 IEC expression predicts mucosal relapse in UC patients in clinical remission [1,3]. Since IL22 promotes mucosal healing and defense through activation of STAT3 and SOCS3 inhibits STAT3 signaling, we investigated whether overexpression of SOCS3 reduced the role of IL22 in mucosal healing and defense .
IL22 expression was accessed with biopsies from patients with active UC, inactive UC and healthy controls by immunohistochemistry. In vitro, impact of SOCS3 overexpression on expression of antimicrobial molecules and mucins were performed by RT-qPCR, cell proliferation was analyzed by CCK8 and cell counting and IEC migration by wounding assays. Signal transduction was analyzed by western blot experiments.
Patients with active UC and inactive UC had significantly more IL22 positive immune cells than healthy controls. SOCS3 overexpression reduced IL22 induced expression of antimicrobial molecules and mucins, inhibited cell proliferation and IL22 promoted IEC migration. SOCS3 overexpression abrogated IL22 induced STAT3 activation and reduced activation of ERK1/2.
SOCS3 overexpression reduced effects of IL22 on mucosal healing and defense. These data strengthen our hypothesis that SOCS3 enhanced vulnerability of IEC during remission may partly due to its counterregulation of protective effects of IL22.
1. Li, Y, Nuij VJ, Baars JE, et al. (2012), Increased suppressor of cytokine signaling-3 expression predicts mucosal relapse in ulcerative colitis.
2. Pickert, G, Neufert C, Leppkes M, et al. (2009), STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing.
3. Li, Y, de Haar C, Chen M, et al, (2010), Disease-related expression of the IL6/STAT3/SOCS3 signalling pathway in ulcerative colitis and ulcerative colitis-related carcinogenesis.