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- Title
Citrobacter rodentium infection causes iNOS-independent intestinal epithelial dysfunction in mice.
- Authors
Skinn, Andrew C.; Vergnolle, Nathalie; Zamuner, Stella R.; Wallace, John L.; Cellars, Laurie; MacNaughton, Wallace K.; Sherman, Philip M.
- Abstract
Attaching-effacing bacteria are major causes of infectious diarrhea in humans worldwide. Citrobacter rodentium is an attaching-effacing enteric pathogen that causes transmissible murine colonic mucosal hyperplasia. We characterized colonic inflammation and ion transport at 3, 7, 10, 30, and 60 d after infection of C57Bl/6 mice with C. rodentium. Macroscopic damage score was significantly increased 7 and 10 d after infection. Colonic wall thickness was increased at 7, 10, 30, and 60 d. Myeloperoxidase (MPO) activity was significantly increased at 3, 7, and 10 d and returned to control levels by days 30 and 60. The expressions of inducible nitric oxide synthase and cyclooxygenase-2 were increased by C. rodentium infection. Significant reductions in the epithelial secretory response to carbachol, but not to electrical field stimulation or forskolin, were observed at 3 and 10 d of infection. Translocation of enteric bacteria into the mesenteric lymph nodes was observed 10 d following infection. There was no difference in response to infection between animals deficient in inducible nitric oxide synthase and wild-type controls. The COX-2 inhibitor rofecoxib caused decreased wall thickness and MPO activity at day 10. However, COX-2 inhibition did not alter infection-induced changes in ion transport. Citrobacter rodentium infection causes colonic inflammation, mucosal hyperplasia, and nitric-oxide-independent epithelial dysfunction in association with increased permeability to luminal bacteria.
- Subjects
DIARRHEA; PATHOGENIC microorganisms; HYPERPLASIA; INTESTINAL diseases; FORSKOLIN; ROFECOXIB; CYCLOOXYGENASE 2
- Publication
Canadian Journal of Physiology & Pharmacology, 2006, Vol 84, Issue 12, p1301
- ISSN
0008-4212
- Publication type
Article
- DOI
10.1139/Y06-086