Molecular analysis of suppression of interleukin-8 production by rebamipide in Helicobacter pylori-stimulated gastric cancer cell lines

M. Aihara, A. Azuma, H. Takizawa, D. Tsuchimoto, Y. Funakoshi, Y. Shindo, Y. Ohmoto, K. Imagawa, M. Kikuchi, N. Mukaida, K. Matsushima

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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-κB 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-κB 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.

Original languageEnglish
Pages (from-to)174S-180S
JournalDigestive Diseases and Sciences
Volume43
Issue number9 SUPPL.
Publication statusPublished - Oct 3 1998
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Physiology
  • Gastroenterology

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