Citrobacter rodentium infection causes iNOS-independent intestinal epithelial dysfunction in mice

Can J Physiol Pharmacol. 2006 Dec;84(12):1301-12. doi: 10.1139/y06-086.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Translocation
  • Carbachol / pharmacology
  • Cell Membrane Permeability
  • Cholinergic Agonists / pharmacology
  • Citrobacter rodentium*
  • Colitis / metabolism*
  • Colitis / microbiology
  • Colitis / pathology
  • Colitis / physiopathology
  • Colon / drug effects
  • Colon / metabolism*
  • Colon / microbiology
  • Colon / pathology
  • Colon / physiopathology
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Enterobacteriaceae Infections / complications
  • Enterobacteriaceae Infections / metabolism*
  • Enterobacteriaceae Infections / microbiology
  • Enterobacteriaceae Infections / pathology
  • Enterobacteriaceae Infections / physiopathology
  • Hyperplasia
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / physiopathology
  • Intestinal Secretions / metabolism
  • Ion Transport
  • Lactones / pharmacology
  • Lymph Nodes / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nitric Oxide Synthase Type II / deficiency
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism*
  • Peroxidase / metabolism
  • Sulfones / pharmacology
  • Time Factors

Substances

  • Cholinergic Agonists
  • Cyclooxygenase 2 Inhibitors
  • Lactones
  • Sulfones
  • rofecoxib
  • Carbachol
  • Peroxidase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2