Helicobacter pylori inhibits gastric cell cycle progression

Helicobacter pylori infection of the gastric mucosa is associated with chan ges in gastric epithelial cell proliferation. In vitro studies have shown t hat exposure to H. pylori inhibits proliferation of gastric cells. This stu dy sought to investigate the cell cycle progression of gastric epithelial c ell lines in the presence and absence of H. pylori. Unsynchronized and sync hronized gastric epithelial cell lines AGS and KatoIII were exposed to H. p ylori over a 24-h period. Cell cycle progression was determined by flow cyt ometry using propidium iodide (PI), and by analysis of cyclin E, p21, and p 53 protein expression using Western blots. In the absence of H. pylori 40, 45, and 15 % of unsynchronized AGS cells were in G(0)-G(1), S, and G(2)-M p hases, respectively, by flow cytometry analysis. When AGS cells were cultur ed in the presence of H. pylori, the S phase decreased 10% and the G(0)-G(1 ) phase increased 17% after 24 h compared with the controls. KatoIII cells, which have a deleted p53 gene, showed little or no response to H. pylori. When G1/S synchronized AGS cells were incubated with media containing H. py lori, the G(1) phase increased significantly (25%, P < 0.05) compared with controls after 24 h. In contrast, the control cells were able to pass throu gh S phase. The inhibitory effects of H. pylori on the cell cycle of AGS ce lls were associated with a significant increase in p53 and p21 expression a fter 24 h. The expression of cyclin E was downregulated in AGS cells follow ing exposure of AGS cells to H. pylori for 24 h. This study shows that H. p ylori-induced growth inhibition in vitro is predominately at the G(0)-G(1) checkpoint. Our results suggest that p53 may be important in H. pylori-indu ced cell cycle arrest. These results support: a role for cyclin-dependent k inase inhibitors in the G(2) cell cycle arrest exerted by fi. pylori and it s involvement in changing the regulatory proteins, p53, p21, and cyclin E i n the cell cycle. (C) 2000 Editions scientifiques et medicales Elsevier SAS .