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J Infect Dis. 2004 Jun 1;189(11):2110-9. Epub 2004 Apr 30.

Differential effects of varying concentrations of clostridium difficile toxin A on epithelial barrier function and expression of cytokines.

Author information

1
Division of Gastroenterology, University Hospital, Queen's Medical Centre, Nottingham, United Kingdom.

Abstract

BACKGROUND:

Presentation after Clostridium difficile infection may depend on the level of epithelial exposure to toxins. We investigated epithelial barrier function and expression of interleukin (IL)-8 and transforming growth factor (TGF)-beta in response to varying concentrations of C. difficile toxin A.

METHODS:

T84 cells were either preexposed or continuously exposed to C. difficile toxin A (0.01-1000 ng/mL). Barrier function was assessed by measurements of transepithelial electrical resistance.

RESULTS:

Preexposure to < or =10 ng/mL toxin A led to an increase in the release of TGF-beta 1, but there was no change in the expression of IL-8. In contrast, after preexposure to >10 ng/mL toxin A, there was enhanced expression of IL-8, but release of TGF-beta 1 was similar to that in control monolayers. After preexposure to >10 ng/mL toxin A, there was complete and irreversible loss of electrical resistance. At lower concentrations, loss of resistance across monolayers was followed by recovery, which was enhanced by all 3 recombinant isoforms of TGF-beta. Pretreatment with recombinant isoforms of TGF-beta or coculture with TGF-beta 3-expressing colonic subepithelial myofibroblasts was also protective.

CONCLUSIONS:

In C. difficile infection, the development and severity of colonic inflammation may depend on the exposure of intestinal epithelial cells to toxins and the expression of proinflammatory (IL-8) and protective (TGF-beta) factors.

PMID:
15143480
DOI:
10.1086/386287
[Indexed for MEDLINE]

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