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 b etween 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 ce ll growth, DNA synthesis, induction of apoptosis, and viability of hum an gastric epithelial cells in vitro. Methods: H. pylori was incubated with a differentiated human gastric cancer cell line for up to 72 hou rs, and the effects on cell numbers (cell counts and WST-1 assay), DNA synthesis (5-bromo-2'-deoxyuridine assay and [H-3]thymidine incorpora tion), and DNA fragmentation (DNA fluorochrome staining, transmission electron microscopy, and histone enzyme-linked immunosorbent assay) we re assessed. Results: Incubation of gastric epithelial cells with H. p ylori led to a time-and concentration-dependent reduction of epithelia l cell growth and a concomitant induction of DNA fragmentation. At hig h bacteria-cell ratios (>100), inhibition of cell growth was associate d with a reduction in DNA synthesis. Treatment of gastric cells with t umor necrosis factor alpha, a receptor-activating CD95/APO-1/Fas antib ody, and interferon gamma markedly potentiated H. pylori-induced DNA f ragmentation. Conclusions: H. pylori affects gastric epithelial cell g rowth by direct induction of apoptosis and inhibition of DNA synthesis and indirectly by sensitization of epithelial cells for apoptosis ind uced by proinflammatory stimuli.