Effects of Helicobacter pylori on proliferation of gastric epithelial cells in vitro

OBJECTIVE: H. pylori infection of the gastric mucosa has been associated with an increase in gastric epithelial cell proliferation. However, in vitro adherence of H. pylori to gastric epithelial cells is associated with reduced cell proliferation. Reduction of epithelial cell proliferation may contribute to ulcer formation and delay ulcer healing. The following study was undertaken to elucidate the ability of cagA-positive and -negative strains to impede gastric epithelial cell proliferation. METHODS: A human gastric adenocarcinoma cell line (AGS) was overlaid with either cagA-positive or cagA-negative H. pylori strains suspended in cell culture medium. Proliferation of AGS cells was analyzed by performing direct cell counts and by measuring metabolism of a soluble tetrazolium compound (MTS), after exposure to H. pylori for 24 h. RESULTS: When compared with control cells cultured in medium alone, AGS cell proliferation was reduced by 45.6% and 28.5% due to exposure to cagA-negative and cagA-positive strains, respectively. When bacterial-induced cytotoxicity was assessed by measuring release of lactose dehydrogenase (LDH) into the culture medium, cagA-positive strains were shown to induce significantly more cytotoxicity than cagA- negative strains. CONCLUSIONS: These experiments demonstrate that H. pylori exposure to AGS cells significantly reduces cell proliferation. However, cagA-positive strains that induce more cell injury reduce cell proliferation to a lesser extent than cagA-negative strains. Persistent replication of gastric epithelial cells injured by exposure to cagA-positive strains may be partially responsible for the stronger association with gastric cancer in persons infected with cagA-positive H. pylori strains.