title: Bacteroides fragilis enterotoxin induces cyclooxygenase-2 and fluid secretion in intestinal epithelial cells through NF-kappaB activation.
abstract: Bacteroides fragilis produces an approximately 20-kDa heat-labile toxin (B. fragilis enterotoxin, BFT) which is known to be associated with diarrhea. To determine whether cyclooxygenase (COX)-2, via NF-kappaB activation, can contribute to BFT-induced diarrhea, the relationship between COX-2 expression and fluid secretion in BFT-stimulated human intestinal epithelial cells was examined. BFT stimulation increased the expression of COX-2, but not COX-1, in human intestinal epithelial cells. Suppression of the NF-kappaB signal significantly decreased COX-2 expression in response to BFT stimulation. Prostaglandin E2 (PGE2) levels were increased in parallel with COX-2 expression, and, conversely, PGE2 production was significantly inhibited when COX-2 or NF-kappaB activities were suppressed using COX-2 small interfering RNA (siRNA), p65 NF-kappaB subunit siRNA, or a retrovirus encoding the IkappaBalpha superrepressor. In addition, a selective COX-2 inhibitor, NS-398, significantly inhibited the increased cAMP level induced by BFT stimulation. Furthermore, a selective COX-2 inhibitor prevented BFT-induced PGE2 production and ileal fluid secretion in a mouse ileal loop model. These results suggest that the secretory response to BFT stimulation may be mediated by the production of PGE2, through NF-kappaB activation and the up-regulation of COX-2 in intestinal epithelial cells.
authors.affiliation: Department of Microbiology and Institute of Biomedical Science, Hanyang University College of Medicine, Seoul, Korea. jungmogg@hanyang.ac.kr
authors.forename: Jung Mogg
authors.initials: JM
authors.lastname: Kim
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Young Mee
authors.initials: YM
authors.lastname: Yoon
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Oh
authors.forename: Ju Seop
authors.initials: JS
authors.lastname: Kang
authors.forename: Yeong-Jeon
authors.initials: YJ
authors.lastname: Kim
authors.forename: Kyoung-Ho
authors.initials: KH
authors.lastname: Kim
mesh_terms: D000818:Animals; D001441:Bacteroides fragilis / Q000276:immunology*; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000187:drug effects; D003967:Diarrhea / Q000209:etiology; D015232:Dinoprostone / Q000096:biosynthesis; D004768:Enterotoxins / Q000009:adverse effects / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D004768:Enterotoxins; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D034741:RNA, Small Interfering; D000242:Cyclic AMP; D051546:Cyclooxygenase 2; D015232:Dinoprostone