Intestinal Epithelial Cells Exposed to Bacteroides fragilis Enterotoxin Regulate NF-κB Activation and Inflammatory Responses through β-Catenin Expression

Abstract

The Bacteroides fragilis enterotoxin (BFT), a virulence factor of enterotoxigenic B. fragilis (ETBF), interacts with intestinal epithelial cells and can provoke signals that induce mucosal inflammation. Although beta-catenin signaling is reported to be associated with inflammatory responses and BFT is known to cleave E-cadherin linked with beta-catenin, little is known about the beta-catenin-mediated regulation of inflammation in ETBF infection. This study was conducted to investigate the role of beta-catenin as a cellular signaling intermediate in the induction of proinflammatory responses to stimulation of intestinal epithelial cells with BFT. Expression of beta-catenin in intestinal epithelial cells was reduced relatively early after stimulation with BFT and then recovered to normal levels relatively late after stimulation. In contrast, phosphorylation of beta-catenin in BFT-exposed cells occurred at high levels early in stimulation and decreased as time passed. Concurrently, late after stimulation the nuclear levels of beta-catenin were relatively higher than those early after stimulation. Suppression of beta-catenin resulted in increased NF-kappa B activity and interleukin-8 (IL-8) expression in BFT-stimulated cells. However, suppression or enhancement of beta-catenin expression neither altered the phosphorylated I kappa B kinase alpha/beta complex nor activated activator protein 1 signals. Furthermore, inhibition of glycogen synthase kinase 3 beta was associated with increased beta-catenin expression and attenuated NF-kappa B activity and IL-8 expression in BFT-exposed cells. These findings suggest the negative regulation of NF-kappa B-mediated inflammatory responses by beta-catenin in intestinal epithelial cells stimulated with BFT, resulting in attenuation of acute inflammation in ETBF infection.