MOLECULAR ANALYSIS OF SUPPRESSION OF INTERLEUKIN-8 PRODUCTION BY REBAMIPIDE IN HELICOBACTER PYLORI-STIMULATED GASTRIC-CANCER CELL-LINES

Interleukin-8 (IL-8) may play an important role in Heloicobacter pylor i infection-associated chronic active,gastritis and peptic ulcer disea se in human. We have recently reported that a gastric cancer cell line , MKN45, produced a massive amount of IL-8 upon coculture with live H. pylori. Moreover, H. pylori induced the activation of NF-kappa B as w ell as AP-1, leading to IL-8 gene transcription. In this study, we eva luated the effect of rebamipide, an antigastritis and antiulcer agent, on H. pylori-induced IL-8 production. Rebamipide inhibited the produc tion of IL-8 in several gastric cancer cell lines infected with H. pyl ori. In addition, rebamipide suppressed H. pylori-induced IL-S gene ex pression at the transcriptional level as revealed by northern blotting analysis and luciferase activity in cells that were transfected with a luciferase expression vector linked with a 5'-flanking region of the IL-8 gene (bp -133 to +44). Furthermore, rebamipide significantly sup pressed the NF-kappa B activation by H, pylori infection. These result s suggest that rebamipide may protect against the mucosal inflammation associated with H. pylori infection through inhibition of a proinflam matory cytokine, IL-8.