title: Bacteroides fragilis enterotoxin upregulates intercellular adhesion molecule-1 in endothelial cells via an aldose reductase-, MAPK-, and NF-κB-dependent pathway, leading to monocyte adhesion to endothelial cells.
abstract: Enterotoxigenic Bacteroides fragilis (ETBF) produces a ∼ 20-kDa heat-labile enterotoxin (BFT) that plays an essential role in mucosal inflammation. Although a variety of inflammatory cells is found at ETBF-infected sites, little is known about leukocyte adhesion in response to BFT stimulation. We investigated whether BFT affected the expression of ICAM-1 and monocytic adhesion to endothelial cells (ECs). Stimulation of HUVECs and rat aortic ECs with BFT resulted in the induction of ICAM-1 expression. Upregulation of ICAM-1 was dependent on the activation of IκB kinase (IKK) and NF-κB signaling. In contrast, suppression of AP-1 did not affect ICAM-1 expression in BFT-stimulated cells. Suppression of NF-κB activity in HUVECs significantly reduced monocytic adhesion, indicating that ICAM-1 expression is indispensable for BFT-induced adhesion of monocytes to the endothelium. Inhibition of JNK resulted in a significant attenuation of BFT-induced ICAM-1 expression in ECs. Moreover, inhibition of aldose reductase significantly reduced JNK-dependent IKK/NF-κB activation, ICAM-1 expression, and adhesion of monocytes to HUVECs. These results suggest that a signaling pathway involving aldose reductase, JNK, IKK, and NF-κB is required for ICAM-1 induction in ECs exposed to BFT, and may be involved in the leukocyte-adhesion cascade following infection with ETBF.
authors: Department of Microbiology, Hanyang University College of Medicine, Seoul 133-791, Korea.
authors: Hyun Cheol
authors: HC
authors: Roh
authors: Do Young
authors: do Y
authors: Yoo
authors: Su Hyuk
authors: SH
authors: Ko
authors: Young-Jeon
authors: YJ
authors: Kim
authors: Jung Mogg
authors: JM
authors: Kim
mesh_terms: D000449:Aldehyde Reductase / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D001442:Bacteroides Infections / Q000276:immunology* / Q000378:metabolism; D001441:Bacteroides fragilis / Q000276:immunology* / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D002460:Cell Line; D042783:Endothelial Cells / Q000276:immunology* / Q000378:metabolism; D004768:Enterotoxins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000276:immunology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000276:immunology* / Q000378:metabolism; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology*
chemical_list: D004768:Enterotoxins; D016328:NF-kappa B; D018799:Intercellular Adhesion Molecule-1; D000449:Aldehyde Reductase; D020929:Mitogen-Activated Protein Kinase Kinases