Role of apoptosis and CD95-receptor/ligand system in aspirin- and Helicobacter pylori-induced cell death.
BACKGROUND
Helicobacter pylori and aspirin both induce gastric epithelial apoptosis. However, the apoptosis-inducing mechanism of aspirin is still unknown.


METHODS
Apoptosis induction was measured in several gastric epithelial cell lines after incubation with either aspirin or H. pylori supernatant or with a combination of both. CD95 expression was assessed by FACS analysis and CD95L mRNA was measured by reverse transcription polymerase chain reaction.


RESULTS
It could be demonstrated that aspirin- and H. pylori supernatant-induced apoptosis involves increased CD95 expression in three different gastric epithelial cell lines. The combined exposure of H. pylori supernatant and aspirin had synergistic effects on both apoptotic cell death and CD95 expression. Blockade of CD95 signalling with an antagonistic antibody was partially prevented from H. pylori- but not from aspirin-induced apoptosis. Furthermore, CD95L expression was detected after treatment with H. pylori only.


CONCLUSIONS
These data suggest that although aspirin-mediated CD95 up-regulation is not relevant for its direct apoptotic effect it may sensitize gastric epithelial cells for H. pylori-induced apoptosis. Collectively our data demonstrate the relation of aspirin- and H. pylori-induced apoptosis from a new perspective.
Domhan
S
S
Department of Medicine, University of Heidelberg, Heidelberg, Germany.
Stremmel
W
W
Rudi
J
J
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001241:Aspirin / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D053222:Fas Ligand Protein; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000502:physiology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D017077:Culture Media, Conditioned; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019014:fas Receptor; D001241:Aspirin