Epithelial intestinal cell apoptosis induced by Helicobacter pylori depends on expression of the cag pathogenicity island phenotype.
Helicobacter pylori has been shown to induce chronic active gastritis and peptic ulcer and may contribute to the development of duodenal ulcer. Previous studies have shown that H. pylori mediates apoptosis of gastric epithelial cells via a Fas-dependent pathway. However, evidence for the induction of such a mechanism in intestinal epithelial cells (IEC) by H. pylori infection has not been demonstrated yet. This study was performed (i) to ascertain that H. pylori can induce IEC apoptosis; (ii) to delineate the role of the cag pathogenicity island (PAI), cagE, and vacA gene products in this process; and (iii) to verify whether the Fas-dependent pathway is involved in this phenomenon. When T84 cells were exposed to VacA(+)/cag PAI(+) H. pylori strains (CCUG 17874 and 60190), they exhibited apoptosis hallmarks as assessed by morphological studies, as well as annexin V and 3,3'-dihexyloxacarbocyanine iodide staining. In contrast, few or no apoptotic features could be detected after incubation with an isogenic mutant of strain 60190 in which the cagE gene was disrupted (60190:C(-) strain) or with a VacA(-)/cag PAI(-) H. pylori strain (G21). In addition, activation of caspase-3 during infection with VacA(+)/cag PAI(+) H. pylori strains was inhibited by pretreatment of IEC with an antagonistic anti-Fas antibody (ZB4). Taken together, these findings indicate that H. pylori triggers apoptosis in IEC via a Fas-dependent pathway following a process that depends on the expression of the cag PAI.
Le'Negrate
G
G
INSERM 364, IFR 50, 06107 Nice Cedex 01, France.
Ricci
V
V
Hofman
V
V
Mograbi
B
B
Hofman
P
P
Rossi
B
B
D017209:Apoptosis; D001426:Bacterial Proteins / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000166:cytology / Q000382:microbiology; D005434:Flow Cytometry / Q000379:methods; D016480:Helicobacter pylori / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology* / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010641:Phenotype; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism
D001426:Bacterial Proteins; C103937:PicB protein, Helicobacter pylori; C074689:VacA protein, Helicobacter pylori; D019014:fas Receptor; D020928:Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases