Intestinal epithelial cells exposed to bacteroides fragilis enterotoxin regulate NF-ĸB activation and inflammatory responses through β-catenin expression

Jong Ik Jeon, Su Hyuk Ko, Jung Mogg Kim

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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 β-catenin signaling is reported to be associated with inflammatory responses and BFT is known to cleave E-cadherin linked with β-catenin, little is known about the β-catenin-mediated regulation of inflammation in ETBF infection. This study was conducted to investigate the role of β-catenin as a cellular signaling intermediate in the induction of proinflammatory responses to stimulation of intestinal epithelial cells with BFT. Expression of β-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 β-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 β-catenin were relatively higher than those early after stimulation. Suppression of β-catenin resulted in increased NF-ĸB activity and interleukin-8 (IL-8) expression in BFT-stimulated cells. However, suppression or enhancement of β-catenin expression neither altered the phosphorylated IĸB kinase α/β complex nor activated activator protein 1 signals. Furthermore, inhibition of glycogen synthase kinase 3β was associated with increased β-catenin expression and attenuated NF-ĸB activity and IL-8 expression in BFT-exposed cells. These findings suggest the negative regulation of NF-ĸB-mediated inflammatory responses by β-catenin in intestinal epithelial cells stimulated with BFT, resulting in attenuation of acute inflammation in ETBF infection.

Original languageEnglish (US)
Article numbere00312-19
JournalInfection and immunity
Volume87
Issue number11
DOIs
StatePublished - 2019
Externally publishedYes

Keywords

  • Bacteroides fragilis
  • Enterotoxin
  • Intestinal epithelial cells
  • NK-ĸB
  • β-catenin

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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