Open AccessInterleukin‐1 receptor phosphorylation activates Rho kinase to disrupt human gastric tight junctional claudin‐4 during Helicobacter pylori infection
Author(s) -
Lapointe Tamia K.,
O'Connor Pamela M.,
Jones Nicola L.,
Menard Daniel,
Buret Andre G.
Publication year - 2010
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2010.01429.x
Subject(s) - tight junction , biology , claudin , helicobacter pylori , caga , phosphorylation , secretion , microbiology and biotechnology , pathogenesis , gastric mucosa , kinase , immunology , stomach , virulence , endocrinology , biochemistry , gene , genetics
Summary Helicobacter pylori infects more than half of the human population worldwide. In the absence of treatment, this persistent infection leads to asymptomatic gastritis, which in some cases can progress into gastric ulcers and adenocarcinomas. The host–microbial interactions that govern the clinical outcome of infection remain incompletely understood. H. pylori is known to disrupt gastric epithelial tight junctions, which may represent a significant component of disease pathogenesis. The present study demonstrates that H. pylori disrupt epithelial tight junctional claudin‐4 in a Rho kinase (ROCK)‐dependent manner in human gastric epithelial (HGE‐20) cell monolayers, independently of the virulence factors CagA and VacA, and without altering claudin‐4 transcription. In the same epithelial cell model, interleukin (IL)‐1β, mediated a similar ROCK‐dependent pattern of tight junction disruption. Further experiments revealed that H. pylori infection induced IL‐1 receptor type I (IL‐1RI) phosphorylation, independently of epithelial secretion of its endogenous ligands IL‐1α, IL‐1β or IL‐18. Finally, inhibition of IL‐1RI activation prevented H. pylori ‐induced ROCK activation and claudin‐4 disruption. Taken together, these findings identify a novel pathophysiological mechanism by which H. pylori disrupts gastric epithelial barrier structure via IL‐1RI‐dependent activation of ROCK, which in turn mediates tight junctional claudin‐4 disruption.