title: Helicobacter pylori impedes acid-induced tightening of gastric epithelial junctions.
abstract: Gastric infection by Helicobacter pylori is the most common cause of ulcer disease and gastric cancer. The mechanism of progression from gastritis and inflammation to ulcers and cancer in a fraction of those infected is not definitively known. Significant acidity is unique to the gastric environment and is required for ulcer development. The interplay between gastric acidity and H. pylori pathogenesis is important in progression to advanced disease. The aim of this study was to characterize the impact of acid on gastric epithelial integrity and cytokine release and how H. pylori infection alters these responses. Human gastric epithelial (HGE-20) cells were grown on porous inserts, and survival, barrier function, and cytokine release were studied at various apical pH levels in the presence and absence of H. pylori. With apical acidity, gastric epithelial cells demonstrate increased barrier function, as evidenced by increased transepithelial electrical resistance (TEER) and decreased paracellular permeability. This effect is reduced in the presence of wild-type, but not urease knockout, H. pylori. The epithelial inflammatory response is also modulated by acidity and H. pylori infection. Without H. pylori, epithelial IL-8 release decreases in acid, while IL-6 release increases. In the presence of H. pylori, acidic pH diminishes the magnitude of the previously reported increase in IL-8 and IL-6 release. H. pylori interferes with the gastric epithelial response to acid, contributing to altered barrier function and inflammatory response. H. pylori diminishes acid-induced tightening of cell junctions in a urease-dependent manner, suggesting that local pH elevation promotes barrier compromise and progression to mucosal damage.
authors.affiliation: DGSOM at UCLA, VA GLAHS, 11301 Wilshire Blvd., Bldg. 113, Rm. 324, Los Angeles, CA 90073. dscott@UCLA.edu.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Marcus
authors.forename: Olga
authors.initials: O
authors.lastname: Vagin
authors.forename: Elmira
authors.initials: E
authors.lastname: Tokhtaeva
authors.forename: George
authors.initials: G
authors.lastname: Sachs
authors.forename: David R
authors.initials: DR
authors.lastname: Scott
mesh_terms: D045744:Cell Line, Tumor; D003470:Culture Media / Q000737:chemistry; D017097:Electric Impedance; D055724:Electrophysiological Phenomena; D004847:Epithelial Cells / Q000187:drug effects* / Q000382:microbiology*; D015964:Gene Expression Regulation, Bacterial; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration
chemical_list: D003470:Culture Media
keywords: Helicobacter pylori; apical acidity; gastric epithelium