Vacuolating cytotoxin of Helicobacter pylori induces apoptosis in the human gastric epithelial cell line AGS

Helicobacter pylori induces cell death by apoptosis. However, the apoptosis -inducing factor is still unknown. The virulence factor vacuolating cytotox in A (VacA) is a potential candidate, and thus its role in apoptosis induct ion was investigated in the human gastric epithelial cell line AGS. The sup ernatant from the vacA wild-type strain P12 was able to induce apoptotic ce ll death, whereas the supernatant from its isogenic mutant strain P14 could not. That VacA was indeed the apoptosis-inducing factor was demonstrated f urther by substantial reduction of apoptosis upon treatment of AGS cells wi th a supernatant specifically depleted of native VacA. Furthermore, a recom binant VacA produced in Escherichia coli was also able to induce apoptosis in AGS cells but failed to induce cellular vacuolation. These findings demo nstrate that the vacuolating cytototoxin of H. pylori is a bacterial factor capable of inducing apoptosis in gastric epithelial cells.