Chronic Helicobacter pylori
infection is associated with alterations in gastric mucosal cell proliferation. Despite the recognition that bacterial
lipopolysaccharide (LPS) is present in biologically active quantities in the gastric mucosa, the mechanisms by which it stimulates cells are largely unknown. We have previously established a gastric enterochromaffin-like (ECL) cell
neoplasia model in the African rodent species Mastomys and identified that
tumor ECL cell proliferation is associated with
polyamine biosynthesis and
ornithine decarboxylase (ODC) activity. In addition, we have shown that H. pylori LPS exhibits a specific mitogenic effect on naive ECL cells in vitro. The aim of this study was to evaluate whether H. pylori has a direct effect on
tumor ECL cell proliferation in vitro and further to evaluate the possible molecular mechanisms for this effect. ECL cell
neoplasia was generated in Mastomys by endogenous hypergastrinemia induced by H(2) blockade (
loxtidine 1 g/kg/day) and
tumor ECL cells prepared. The
DNA synthesis in 24-hour cultured tumor cells was measured by
bromodeoxyuridine uptake and ODC activity by (14)CO(2) formation from (14)C-ornithine. The putative
LPS receptor, CD14, was evaluated by reverse-transcription polymerase chain reaction. Our results demonstrated: (1) H. pylori LPS (10(-12) to 10(-7) M) stimulated basal
DNA synthesis (2.2-fold) with an estimated EC(50) of 10(-10) M; (2) this proliferative response correlated with an increase in ODC activity (1.4-fold, EC(50) approximately 10(-10) M) which could be inhibited by a specific ODC inhibitor, difluoromethyl
ornithine,
at 10(-9) M; (3) the CD14 receptor was identified in both naive and transformed ECL cells by reverse-transcription polymerase chain reaction, and (4) the effects of LPS were inhibited by blocking the CD14 receptor with its specific
monoclonal antibody (1:100). Thus, H. pylori LPS appears to influence
tumor ECL cell proliferation by activation of the intracellular
polyamine pathway and ODC activity via a CD14 receptor on the ECL cell.