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 language | English (US) |
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Article number | e00312-19 |
Journal | Infection and immunity |
Volume | 87 |
Issue number | 11 |
DOIs | |
State | Published - 2019 |
Externally published | Yes |
Keywords
- Bacteroides fragilis
- Enterotoxin
- Intestinal epithelial cells
- NK-ĸB
- β-catenin
ASJC Scopus subject areas
- Parasitology
- Microbiology
- Immunology
- Infectious Diseases