Proteolytic activity of the Bacteroides fragilis enterotoxin causes fluid secretion and intestinal damage in vivo

Obiso, Richard J.; Lyerly, David M.; Tassell, Roger L. Van; Wilkins, Tracy D.

doi:10.1128/iai.63.10.3820-3826.1995

Cited by 90 publications

(57 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since the infiltration of neutrophils occurs in vivo in response to enterotoxigenic B. fragilis [6,7], we investigated whether this phenomenon could be mediated by NF-kB activation in BFTstimulated intestinal epithelial cells. Our results revealed that BFT stimulation of the apical membrane of intestinal epithelial cells induced neutrophil transmigration.…”

Section: Discussionmentioning

confidence: 99%

“…Intestinal epithelial cells are structurally and functionally polarized in vivo. Since a significant infiltration of neutrophils occurs in vivo in response to enterotoxigenic B. fragilis infection [6,7], we investigated whether this phenomenon could be mediated by NF-kB activation using a polarized intestinal epithelial T84 cell line. By using an inverted monolayer system [26,27], the apical surface of the cultured monolayers was stimulated with BFT and…”

Section: Inhibition Of Nf-kb Signals Decreases Neutrophil Transepithementioning

confidence: 99%

“…The inflammatory response to ETBF is attributed to the expression of a ~20 kD heat-labile metalloprotease toxin (B. fragilis enterotoxin, or BFT). BFT was reported to induce morphological changes of intestinal epithelial cells [3][4][5][6]. Histological examination revealed that the inoculation of ETBF or BFT to intestinal lumen caused mucosal inflammation characterized by the infiltration of neutrophils [6,7].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A bibliometric analysis of publications by the Chemistry Department, Seoul National University, Korea, 1992-1998

Kim

2000

Journal of Information Science

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Section: Inhibition Of Nf-kb Signals Decreases Neutrophil Transepithementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A bibliometric analysis of publications by the Chemistry Department, Seoul National University, Korea, 1992-1998

Kim

2000

Journal of Information Science

View full text Add to dashboard Cite

“…BFT stimulates intestinal epithelial cell morphologic changes [3,5,6]. Histological examination revealed that the inoculation of ETBF or BFT to intestinal lumen caused mucosal inflammation characterized by the infiltration of neutrophils [6,7].…”

Section: Introductionmentioning

confidence: 98%

Polarized secretion of CXC chemokines by human intestinal epithelial cells in response toBacteroides fragilisenterotoxin: NF-κB plays a major role in the regulation of IL-8 expression

Kim

et al. 2001

Clinical and Experimental Immunology

157

View full text Add to dashboard Cite

SUMMARYEnterotoxigenic B. fragilis, which produces a ,20 kD heat-labile toxin (BFT), has been associated with diarrhoeal diseases and mucosal inflammation. To determine if epithelial cells can contribute to BFTinduced inflammation, we assessed the expression of CXC chemokines by BFT-stimulated human intestinal epithelial cells. BFT stimulation increased expression of the neutrophil chemoattractant and activators ENA-78, GRO-a , and IL-8. Up-regulated chemokine mRNA expression was paralleled by increased protein levels. Activation of the IL-8 and NF-kB transcriptional reporters was inhibited in cells cotransfected with the IkB kinase b and IkBa superrepressor plasmids. Whereas lactate dehydrogenase, which was used to monitor cell lysis, was released predominantly from the apical surface, CXC chemokines were predominantly secreted from the basolateral surface of BFT-treated epithelial cells. The basolateral secretion of CXC chemokines from BFT-stimulated colon epithelial cells suggests that these chemokines can contribute to the inflammatory cell infiltrate in the underlying intestinal mucosa.

show abstract

“…Enterotoxigenic Bacteroides fragilis (ETBF) has been shown to be associated with non-invasive diarrheal diseases in animals and young children [1][2][3][4][5], and B. fragilis enterotoxin (BFT), an approximately 20-kDa heat-labile metalloprotease, is regarded as a virulence factor for this diarrheal disease. BFT stimulates NF-jB activation and IL-8 secretion [6][7][8][9], which is predicted to lead to mucosal transmigration of neutrophils with release of prostaglandins (PG).…”

Section: Introductionmentioning

confidence: 99%

Bacteroides fragilisenterotoxin induces cyclooxygenase‐2 and fluid secretion in intestinal epithelial cells through NF‐κB activation

et al. 2006

View full text Add to dashboard Cite

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-jB 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-jB signal significantly decreased COX-2 expression in response to BFT stimulation. Prostaglandin E 2 (PGE 2 ) levels were increased in parallel with COX-2 expression, and, conversely, PGE 2 production was significantly inhibited when COX-2 or NF-jB activities were suppressed using COX-2 small interfering RNA (siRNA), p65 NF-jB subunit siRNA, or a retrovirus encoding the IjBa 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 BFTinduced PGE 2 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 PGE 2 , through NF-jB activation and the up-regulation of COX-2 in intestinal epithelial cells. IntroductionEnterotoxigenic Bacteroides fragilis (ETBF) has been shown to be associated with non-invasive diarrheal diseases in animals and young children [1][2][3][4][5], and B. fragilis enterotoxin (BFT), an approximately 20-kDa heat-labile metalloprotease, is regarded as a virulence factor for this diarrheal disease. BFT stimulates NF-jB activation and IL-8 secretion [6][7][8][9], which is predicted to lead to mucosal transmigration of neutrophils with release of prostaglandins (PG). In addition, animal loop experiments and gnotobiotic piglet infection indicate that BFT is proinflammatory and BFT stimulates a brief chloride current and a loss of barrier function in vitro [3,10], suggesting that these findings are potential mechanisms accounting for ETBF-induced diarrhea. Several studies have shown that secretion of PG from intestinal mucosal epithelial cells is closely associated with diarrheal diseases [11,12], and administration of PG analogues, such as PGE 2 , causes increased fluid secretion in human subjects [13,14]. In addition, the roles of PG in the secretory response to cholera toxin and enterotoxigenic Escherichia coli have been demonstrated [15][16][17]. These results suggest the hypothesis that the diarrhea associated with ETBF may be PG-derived. PGE 2 is a metabolite of arachidonic acid and is synthesized by cyclooxygenase (COX). There are two isoforms of this enzyme [18]: COX-1, which is constitutively expressed in crypt epithelial cells, and COX-2, which can be induced in a variety of cell types, including epithelial cells, macrophages and fibroblasts. COX-2 is induced by proinflammatory cytokines, lipopolysaccharide and infectious agents [19]. The expr...

show abstract

Proteolytic activity of the Bacteroides fragilis enterotoxin causes fluid secretion and intestinal damage in vivo

Cited by 90 publications

References 32 publications

A bibliometric analysis of publications by the Chemistry Department, Seoul National University, Korea, 1992-1998

A bibliometric analysis of publications by the Chemistry Department, Seoul National University, Korea, 1992-1998

Polarized secretion of CXC chemokines by human intestinal epithelial cells in response toBacteroides fragilisenterotoxin: NF-κB plays a major role in the regulation of IL-8 expression

Bacteroides fragilisenterotoxin induces cyclooxygenase‐2 and fluid secretion in intestinal epithelial cells through NF‐κB activation

Contact Info

Product

Resources

About