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Helicobacter pylori disrupts gastric epithelial barrier structure and function in an MLCK and ROCK dependent fashion
Author(s) -
Lapointe Tamia Kateri,
O'Connor Pamela M.,
Fedwick Jason P.,
Meddings Jon,
Menard Daniel,
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.20.5.a1095
Subject(s) - myosin light chain kinase , paracellular transport , barrier function , tight junction , helicobacter pylori , permeability (electromagnetism) , epithelium , foveolar cell , claudin , chemistry , gastric mucosa , microbiology and biotechnology , biology , stomach , myosin , medicine , pathology , biochemistry , membrane
H. pylori (Hp) causes gastritis, gastroduodenal ulcers, and gastric cancer in humans. The ability of Hp strains to disrupt epithelial barrier function may influence the clinical outcome of infection. The effects of Hp on gastric epithelial permeability remain incompletely understood. AIM The aim of this study was to characterize the effects of Hp on gastric permeability in vivo and in vitro . RESULTS Infection with Hp strain SS1 increased gastric permeability to an oral sucrose probe in mice. Direct effects of Hp SS1 on epithelial permeability were assessed on human gastric epithelial (HGE‐20) monolayers. Immunocytochemistry, western blotting, and apical‐to‐basolateral fluxes of FITC‐dextran revealed that Hp SS1 disrupts claudin‐4 and ‐5 and increases paracellular permeability. Hp SS1 induced the tight junction‐to‐cytosol translocation of claudin‐4 and ‐5. Inhibition of myosin light chain kinase (MLCK) or Rho‐kinase (ROCK) prevented these defects. CONCLUSION These data suggest that Hp may directly increase gastric epithelial permeability. Mechanistically, Hp‐induced disruption of claudin‐4 and ‐5, and loss of epithelial barrier function, are mediated in part by MLCK and ROCK.