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Eur J Immunol. 2006 Sep;36(9):2446-56.

Bacteroides fragilis enterotoxin induces cyclooxygenase-2 and fluid secretion in intestinal epithelial cells through NF-kappaB activation.

Author information

1
Department of Microbiology and Institute of Biomedical Science, Hanyang University College of Medicine, Seoul, Korea. jungmogg@hanyang.ac.kr

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.

PMID:
16892182
DOI:
10.1002/eji.200535808
[Indexed for MEDLINE]
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