Rebamipide inhibits ceramide-induced interleukin-8 production in Kato III human gastric cancer cells

Atsushi Masamune, Masayoshi Yoshida, Yoshitaka Sakai, Toru Shimosegawa

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Helicobacter pylori adheres to gastric epithelial cells and stimulates interleukin-8 production. Ceramide, a lipid second messenger, has become known as an important mediator of some actions of several cytokines. We have recently reported that H. pylori-dependent ceramide production may activate nuclear factor-κB and mediate interleukin-8 expression in human gastric cancer cell lines. In this study, we evaluated the effect of rebamipide, an antigastritis and antiulcer agent, on H. pylori-dependent ceramide production and subsequent interleukin-8 expression in Kato III cells. Rebamipide inhibited ceramide-Induced interleukin-8 expression In a dose-dependent manner. Rebamipide decreased the ceramide-induced increase of the interleukin-8 mRNA level as assessed by Northern blottings. Rebamipide suppressed interleukin-8 gene transcription and nuclear factor-κB-dependent transcriptional activity as assessed by luciferase assay. Rebamipide inhibited the ceramide-induced degradation of IκB-α (a major cytoplasmic inhibitor of nuclear factor-κB), further supporting that rebamipide inhibits the activation of nuclear factor-κB. Rebamipide also inhibited the ceramide-dependent activation of mitogen-activated protein kinases. Furthermore, rebamipide significantly attenuated the H. pylori-dependent increase in the intracellular ceramide level. These results suggest a novel mechanism by which rebamipide may protect against the mucosal inflammation associated with H. pylori infection.

Original languageEnglish
Pages (from-to)485-492
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume298
Issue number2
Publication statusPublished - 2001 Aug 2

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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