Bacteroides fragilis Enterotoxin Upregulates Intercellular Adhesion Molecule-1 in Endothelial Cells via an Aldose Reductase-, MAPK-, and NF-kappa B-Dependent Pathway, Leading to Monocyte Adhesion to Endothelial Cells
- Authors
- Roh, Hyun Cheol; Yoo, Do Young; Ko, Su Hyuk; Kim, Young-Jeon; Kim, Jung Mogg
- Issue Date
- Aug-2011
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Citation
- JOURNAL OF IMMUNOLOGY, v.187, no.4, pp.1931 - 1941
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Volume
- 187
- Number
- 4
- Start Page
- 1931
- End Page
- 1941
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/167896
- DOI
- 10.4049/jimmunol.1101226
- ISSN
- 0022-1767
- Abstract
- Enterotoxigenic Bacteroides fragilis (ETBF) produces a similar to 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 I kappa B kinase (IKK) and NF-kappa B signaling. In contrast, suppression of AP-1 did not affect ICAM-1 expression in BFT-stimulated cells. Suppression of NF-kappa B 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-kappa B activation, ICAM-1 expression, and adhesion of monocytes to HUVECs. These results suggest that a signaling pathway involving aldose reductase, JNK, IKK, and NF-kappa B is required for ICAM-1 induction in ECs exposed to BFT, and may be involved in the leukocyte-adhesion cascade following infection with ETBF. The Journal of Immunology, 2011, 187: 1931-1941.
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