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Citrobacter rodentium increases intestinal permeability and disrupts epithelial tight junctions in vivo and in vitro: the role of Rho kinase
Author(s) -
Flynn Andrew N,
Vergnolle Nathalie,
Sharkey Keith,
Buret Andre G
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a201-a
Subject(s) - citrobacter rodentium , tight junction , in vivo , claudin , intestinal epithelium , intestinal mucosa , microbiology and biotechnology , apoptosis , in vitro , biology , paracellular transport , chemistry , permeability (electromagnetism) , epithelium , immunology , biochemistry , medicine , colitis , membrane , genetics
The aim of this study was to identify mechanisms of Citrobacter rodentium ‐induced epithelial permeability defects. RESULTS C. rodentium increased intestinal permeability to 51 Cr‐labeled EDTA and disrupted tight junctional ZO‐1, claudin‐4, and claudin‐5 in vivo. C. rodentium induced apoptotic nucleosome formation and PARP cleavage in CMT‐93 colorectal epithelial cells. Infected monolayers also displayed increased paracellular permeability to a FITC‐dextran probe. This effect was dependent on Rho kinase, but did not require caspase‐3 activity. Immunocytochemistry and Western blotting confirmed the caspase‐3‐independent disruption of ZO‐1, claudin‐4, and claudin‐5 by C. rodentium in vitro . CONCLUSIONS C. rodentium increases intestinal epithelial permeability in vivo and in vitro . This effect is associated with disruptions of ZO‐1, claudin‐4, and claudin‐5. Rho kinase plays a role in C. rodentium ‐induced increases in epithelial permeability. Although C. rodentium induces intestinal epithelial cell apoptosis, its effects on permeability are not dependent on caspase‐3. We postulate that loss of epithelial barrier function is implicated in the pathogenesis of EPEC‐induced intestinal disease.