S100A4 contributes to colitis development by increasing the adherence of Citrobacter rodentium in intestinal epithelial cells.

S100A4 has been implicated in cancer and several inflammatory diseases, but its role in inflammatory bowel disease has not been well investigated. Here, upon infection with Citrobacter rodentium, a model for enteropathogenic Escherichia coli infection in humans, induced the infiltration of a large number of S100A4(+) cells into the colon in wild type (WT) mice. Deficiency of S100A4 reduced weight loss, bacterial colonization and colonic pathology. Furthermore, the expression of inflammatory cytokines and the recruitment of macrophages and neutrophils also decreased significantly in S100A4 knock out (S100A4 (-/-)) mice. In vitro, soluble S100A4 directly up-regulated expression of integrin β-1 in intestinal epithelial cells and significantly increased the adherence of C. rodentium to intestinal epithelial cells. Additionally, the effects of S100A4 on the adherence of C. rodentium to epithelial cells could be abolished by a receptor for advanced glycation end products (RAGE)-specific inhibitor (FPS-ZM1). Therefore, these data indicate a novel mechanism for S100A4 that promotes colitis development by enhancing host adhesion and colonization of Citrobacter rodentium through the S100A4-mediated host inflammatory responses.