Regulation of gastric epithelial cell growth by Helicobacter pylori: Evidence for a major role of apoptosis

Background & Aims: Helicobacter pylori may affect the normal balance between gastric epithelial cell proliferation and epithelial cell death, thus interfering with the maintenance of gastric mucosal integrity. The aim of this study was to investigate the effect of H. pylori on cell growth, DNA synthesis, induction of apoptosis, and viability of human gastric epithelial cells in vitro. Methods: H. pylori was incubated with a differentiated human gastric cancer cell line for up to 72 hours, and the effects on cell numbers (cell counts and WST-1 assay), DNA synthesis (5-bromo-2'-deoxyuridine assay and [H-3]thymidine incorporation), and DNA fragmentation (DNA fluorochrome staining, transmission electron microscopy, and histone enzyme-linked immunosorbent assay) were assessed. Results: Incubation of gastric epithelial cells with H. pylori led to a time-and concentration-dependent reduction of epithelial cell growth and a concomitant induction of DNA fragmentation. At high bacteria-cell ratios (>100), inhibition of cell growth was associated with a reduction in DNA synthesis. Treatment of gastric cells with tumor necrosis factor alpha, a receptor-activating CD95/APO-1/Fas antibody, and interferon gamma markedly potentiated H. pylori-induced DNA fragmentation. Conclusions: H. pylori affects gastric epithelial cell growth by direct induction of apoptosis and inhibition of DNA synthesis and indirectly by sensitization of epithelial cells for apoptosis induced by proinflammatory stimuli.