Introduction Infection with Helicobacter bacteria leads to a chronic superficial gastritis. In some cases this may progress to atrophic gastritis and subsequently gastric adenocarcinoma. Apoptosis is a type of programmed cell death in multicellular organisms and defects in its regulation may contribute towards carcinogenesis. Bak is a pro-apoptotic member of the bcl-2 family of proteins which has been shown to play important roles in the regulation of γ-radiation induced apoptosis in the stomach1 and colonic carcinogenesis in vivo.2 We therefore hypothesise that bak-regulated apoptosis may influence the development of Helicobacter-induced gastric cancer and have investigated whether H felis-induced gastric apoptosis and gastric atrophy are altered in a bak-null mouse model.

Methods An initial time-course to assess the consequences of H felis infection was performed using groups of 6 adult C57BL/6 male mice sacrificed 2, 4, 6, 9, 12 and 20 weeks after infection. Groups of 7 C57BL/6 male mice and 7 bak-null male mice (on a C57BL/6 genetic background) were subsequently infected with H felis for 6 weeks. Histological and immunohistochemical techniques were used to assess the extent of infection, inflammation, bak expression, atrophy (using anti-H⁺/K⁺ ATPase to label parietal cells), cell proliferation (using anti-Mib-1) and apoptosis (using anti-active caspase-3).

Results H felis infection of C57BL/6 mice resulted in an increase in gastric bak expression at 2 weeks and a significant decrease in the number of parietal cells was observed at 6 weeks, which then returned to control levels by 20 weeks. Cell proliferation and apoptosis both increased with time following H felis infection. 6 weeks following H felis infection, bak-null mice showed significantly less gastric atrophy and apoptosis than C57BL/6 mice, but no significant changes in proliferation were observed.

Conclusion Gastric epithelial bak expression, atrophy, proliferation and apoptosis were increased following H felis infection of wild-type mice. After 6 weeks of H felis infection, bak-null mice showed significantly less atrophy and less apoptosis compared to their wild-type counterparts. These data suggest that bak plays a significant role in modulating the short-term consequences of Helicobacter infection in the murine stomach. Further studies at later timepoints following H felis infection are therefore warranted to investigate whether bak expression also regulates the development of gastric carcinoma.