RRC ID 39513
Author Ko SH, Rho da J, Jeon JI, Kim YJ, Woo HA, Lee YK, Kim JM.
Title Bacteroides fragilis Enterotoxin Upregulates Heme Oxygenase-1 in Intestinal Epithelial Cells via a Mitogen-Activated Protein Kinase- and NF-κB-Dependent Pathway, Leading to Modulation of Apoptosis.
Journal Infect Immun
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 expression of heme oxygenase-1 (HO-1) is associated with regulation of inflammatory responses, little is known about HO-1 induction in ETBF infection. This study was conducted to investigate the effect of BFT on HO-1 expression in intestinal epithelial cells. Stimulation of intestinal epithelial cells with BFT resulted in upregulated expression of HO-1. BFT activated transcription factors such as NF-κB, AP-1, and Nrf2 in intestinal epithelial cells. Upregulation of HO-1 in intestinal epithelial cells was dependent on activated IκB kinase (IKK)-NF-κB signals. However, suppression of Nrf2 or AP-1 signals in intestinal epithelial cells did not result in significant attenuation of BFT-induced HO-1 expression. HO-1 induction via IKK-NF-κB in intestinal epithelial cells was regulated by p38 mitogen-activated protein kinases (MAPKs). Furthermore, suppression of HO-1 activity led to increased apoptosis in BFT-stimulated epithelial cells. These results suggest that a signaling pathway involving p38 MAPK-IKK-NF-κB in intestinal epithelial cells is required for HO-1 induction during exposure to BFT. Following this induction, increased HO-1 expression may regulate the apoptotic process in responses to BFT stimulation.
Volume 84(9)
Pages 2541-54
Published 2016-9-1
DOI 10.1128/IAI.00191-16
PII IAI.00191-16
PMID 27324483
PMC PMC4995915
MeSH Animals Apoptosis / immunology* Bacteroides fragilis / immunology* Enterotoxins / immunology* Epithelial Cells / immunology Epithelial Cells / metabolism Epithelial Cells / microbiology* Heme Oxygenase-1 / metabolism* I-kappa B Proteins / metabolism Intestinal Mucosa / metabolism Intestinal Mucosa / microbiology* Mice Mice, Inbred C57BL Mice, Knockout Mitogen-Activated Protein Kinases / metabolism* NF-E2-Related Factor 2 / metabolism NF-kappa B / metabolism* Signal Transduction / immunology Transcription Factor AP-1 / metabolism Transcriptional Activation / immunology Up-Regulation / immunology p38 Mitogen-Activated Protein Kinases / metabolism
IF 3.201
Times Cited 9
Mice RBRC01390