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  • Title: Molecular analysis of suppression of interleukin-8 production by rebamipide in Helicobacter pylori-stimulated gastric cancer cell lines.
    Author: Aihara M, Azuma A, Takizawa H, Tsuchimoto D, Funakoshi Y, Shindo Y, Ohmoto Y, Imagawa K, Kikuchi M, Mukaida N, Matsushima K.
    Journal: Dig Dis Sci; 1998 Sep; 43(9 Suppl):174S-180S. PubMed ID: 9753246.
    Abstract:
    Interleukin-8 (IL-8) may play an important role in Helicobacter pylori infection-associated chronic active gastritis and peptic ulcer disease 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-kappaB as well as AP-1, leading to IL-8 gene transcription. In this study, we evaluated the effect of rebamipide, an antigastritis and antiulcer agent, on H. pylori-induced IL-8 production. Rebamipide inhibited the production of IL-8 in several gastric cancer cell lines infected with H. pylori. In addition, rebamipide suppressed H. pylori-induced IL-8 gene expression 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 suppressed the NF-kappaB activation by H. pylori infection. These results suggest that rebamipide may protect against the mucosal inflammation associated with H. pylori infection through inhibition of a proinflammatory cytokine, IL-8.
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