Regulation of gastric epithelial cell growth by Helicobacter pylori: offdence for a major role of apoptosis.
OBJECTIVE
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 [3H]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.
Wagner
S
S
Department of Gastroenterology, Medizinische Hochschule Hannover, Germany. Wagner.Siegfried@MH-Hannover
Beil
W
W
Westermann
J
J
Logan
R P
RP
Bock
C T
CT
Trautwein
C
C
Bleck
J S
JS
Manns
M P
MP
D017304:Annexin A5; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D006690:Bisbenzimidazole; D002455:Cell Division / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000037:antagonists & inhibitors / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D007211:Indoles; D018836:Inflammation Mediators / Q000494:pharmacology; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D010718:Phosphatidylserines / Q000378:metabolism; D014407:Tumor Cells, Cultured
D017304:Annexin A5; D005456:Fluorescent Dyes; D007211:Indoles; D018836:Inflammation Mediators; D010718:Phosphatidylserines; C007293:DAPI; D004247:DNA; D016650:Fluorescein-5-isothiocyanate; D006690:Bisbenzimidazole