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 p eptic ulcer and may contribute to the development of duodenal ulcer. Previo us studies have shown that H. pylori mediates apoptosis of gastric epitheli al cells via a Fas-dependent pathway. However, evidence for the induction o f such a mechanism in intestinal epithelial cells (IEC) by H. pylori infect ion has not been demonstrated yet. This study was performed (i) to ascertai n that H. pylori can induce IEC apoptosis; (ii) to delineate the role of th e cag pathogenicity island (PAI), cagE, and vacA gene products in this proc ess; and (iii) to verify whether the Fas-dependent pathway is involved in t his phenomenon. When T84 cells were exposed to VacA(+)/cag PAI(+) H. pylori strains (CCUG 17874 and 60190), they exhibited apoptosis hallmarks as asse ssed by morphological studies, as well as annexin V and 3,3'-dihexyloxacarb ocyanine iodide staining. In contrast, few or no apoptotic features could b e detected after incubation with an isogenic mutant of strain 60190 in whic h 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 infec tion with VacA(+)/cag PAI(+) H. pylori strains was inhibited by pretreatmen t of IEC with an antagonistic anti-Fas antibody (ZB4). Taken together, thes e findings indicate that H. pylori triggers apoptosis in IEC via a Fas-depe ndent pathway following a process that depends on the expression of the cag PAI.