Effects of IL-1β on the proliferation and apoptosis of gastric epithelial cells and acid secretion from isolated rabbit parietal cells

The aim of the present study was to explore the effects of IL-1 beta on the proliferation and apoptosis of gastric epithelial cells and acid secretion from isolated rabbit parietal cells. The mechanisms by which these effects are mediated were also investigated. Parietal cells were isolated from rabbit gastric mucosa by elutriation. The AGS human gastric cancer cell line, the GES-1 human gastric epithelial cell line and parietal cells were treated with interleukin (IL)-1 beta in the presence or absence of Helicobacter pylori (H. pylori) for the times indicated. MTT assay and flow cytometry (FCM) were used to determine the levels of proliferation and apoptosis. The expression levels of cyclooxygenase-2 (COX-2) mRNA and protein were examined by RT-PCR and FCM. Acid secretion by parietal cells was examined using C-14-aminopyrine (C-14-AP) accumulation. H+/K(+)ATPase alpha subunit mRNA expression was assessed by RT-PCR. The results demonstrated that IL-1 beta (10 ng/ml) stimulated cellular proliferation and inhibited H. pylori-induced apoptosis in GES-1 and AGS cell lines. IL-1 beta (10 ng/ml) upregulated the mRNA and protein expression of COX-2 in GES-1 and AGS cells. Acid secretion stimulated by histamine was identified as significantly inhibited and mRNA expression of H+/K(+)ATPase alpha subunit was downregulated by treatment with IL-1 beta (10 ng/ml) for 30 min and 16 h compared with the control in isolated rabbit parietal cells. The present study demonstrates that IL-1 beta plays a significant role in H. pylori-induced gastric carcinogenesis through 2 main mechanisms: i) IL-1 beta may interfere in gastric epithelial cell growth by upregulating COX-2 expression; ii) IL-1 beta may inhibit the acid secretion from parietal cells by downregulating H+/K(+)ATPase expression.