Effect of Interlukin-1β on proliferation of gastric epithelial cells in culture

Background: Helicobacter pylori is the main risk factor for the development of non-cardia gastric cancer. Increased proliferation of the gastric mucosa is a feature of H. pylori infection. Mucosal interkeukin-1 beta production is increased in H. pylori infection and IL-1 beta genotypes associated with increased pro-inflammatory activity are risk factors for the development of gastric cancer. The effect of IL-1 beta on gastric epithelial cell proliferation has been examined in this study. Methods: AGS cells were cultured with IL-1 beta . DNA synthesis was assed by [ super(3)H]thymidine incorporation and total viable cell numbers by MTT assay. Results: IL-1 beta dose dependently increased DNA synthesis and cell numbers. The enhanced proliferation was blocked by interleukin-1 receptor antagonist. Addition of neutralising antibody to GM- CSF reduced IL-1 beta -stimulated proliferation by 31 plus or minus 4 %. GM-CSF alone significantly stimulated proliferation. Addition or neutralisation of IL-8 had no effect on basal or IL-1 beta -stimulated proliferation. The tyrosine kinase inhibitor genistein completely blocked IL-1 beta -stimulated proliferation and inhibition of the extracellular signal related kinase pathway with PD 98059 inhibited IL-1 beta stimulated proliferation by 58 plus or minus 5 %. Conclusions: IL-1 beta stimulates proliferation in gastric epithelial cells. Autocrine stimulation by GM-CSF contributes to this proliferative response. Signalling via tyrosine kinase activity is essential to the mitogenic response to IL-1 beta . The extracellular signal related kinase pathway is involved in, but not essential to downstream signalling. IL-1 beta may contribute to the hyperproliferation seen in H. pylori- infected gastric mucosa, and be involved in the carcinogenic process.