Epithelial Nuclear Factor-κB Activation in Inflammatory Bowel Diseases and Colitis-Associated Carcinogenesis

Prolonged inflammatory bowel diseases (IBD) may lead to colitis-associated carcinogenesis (CAC). Previous studies had shown that nuclear factor-κB (NF-κB) activation in both macrophages and epithelia in inflamed colonic tissue is associated with CAC development. However, the mechanism by which epithelial NF-κB activation leading to CAC development had not previously been rigorously studied. We and others had observed the increased expression of the type 2 receptor for tumor necrosis factor (TNFR2/TNFRSF1b/p75) in IBD models. Myosin light chain kinase (MLCK) is suggested to be associated with epithelial permeability via TNF signaling. Therefore, the relationship between epithelial MLCK expression and NF-κB activation via TNFR2 signaling on CAC development was investigated. Pro-tumorigenic cytokines such as interleukin (IL)-1β, IL-6 and macrophage inflammaPublished online: January 14, 2016 Takashi Nagaishi, MD, PhD Department of Gastroenterology and Hepatology Graduate School of Medical Science , Tokyo Medical and Dental University 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 (Japan) E-Mail tnagaishi.gast @ tmd.ac.jp © 2016 S. Karger AG, Basel 0012–2823/16/0931–0040$39.50/0