Epithelial: Helicobacter pylori interactions
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AbstractThe dynamic and selective barrier formed by the epithelial cells of the human gastric mucosa is crucial in the protection against microbial pathogens. Peptides produced by the human host such as epidermal growth factor (EGF) are important in maintaining mucosal integrity and protecting the host from bacterial colonization. This study investigated the effect of H. pylori, a human gastric pathogen implicated in the development of gastroduodenal ulcers and gastric cancers, on epithelial barrier structure and function in vivo and in vitro. In addition, the effect of EGF on H. pylori colonization and viability was also examined. Bacterial load and gastritis increased over 14, 70 and 100 days in C57Bl/6 mice infected with H. pylori strain SS1. Infected mice also had a transient increase in gastric, but not duodenal, permeability on day 73 of the infection. Confluent, non-transformed intestinal epithelial cells (SCBN) grown on Transwells and exposed to H. pylori strain SS1 (VacA+/CagA+) had an increase in the passage of 3000MW Dextran. In contrast, H. pylori strains LC11 (VacA+/CagA+) and LC20 (VacA-/CagA-) did not change the permeability of SCBN cells to 3000MW Dextran. By immunohistochemistry and western blotting, H. pylori strain SS 1 disrupted tight junction (TJ) occludin, claudin-4 and claudin-5 in SCBN cells. The addition of a specific inhibitor of MLCK prevented the increase in epithelial permeability and disruption of tight junctional claudin-4 and claudin-5. Oral, daily administration of human recombinant EGF (100Jµg/kg) to infected mice 10 days prior to sacrifice significantly lowered the number of H. pylori recovered from gastric tissues. However, co-culture of H. pylori and EGF (100µM) had no effect on bacterial growth or metabolism. Stomach sections from infected-EGF treated animals had a different pattern of surface carbohydrate expression compared to infected animals. Disruptions of the tight junction observed in this study implicate previously unrecognized host cell signaling pathways, including the regulation of tight junctional claudin-4, claudin-5 and the phosphorylation of myosin light chain, in the pathogenesis of H. pylori infection. In addition, oral administration of EGF, independent of a direct microbiocidal action, can decrease the colonization of the stomach by H. pylori.
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