The effect of rebamipide on Helicobacter pylori extract-mediated changes of gene expression in gastric epithelial cells

Abstract

Background: Recent studies have shown that Helicobacter pylori affects intracellular signal transduction in host cells, leading to the activation of transcriptional factors and the induction of pro-inflammatory cytokines. On the other hand, rebamipide, an anti-gastritis and anti-ulcer agent, could scavenge reactive oxygen species and reduce interleukin-8 (IL-8) expression in gastric epithelial cells induced by H. pylori-stimulation through the attenuated activation of nuclear factor-κB (NF-κB). Aims: In this study, we investigated the effects of rebamipide on gene expression in H. pylori-stimulated epithelial cells using DNA chip. Methods: H. pylori water extract (HPE) was prepared from NCTC11637, the type strain of H. pylori. Total RNA was extracted from MKN45 cells, a human gastric cancer cell line, following HPE-stimulation with and without rebamipide for 3 h, and differences in gene expression profiles were observed using GeneChip and Human 6800 probe array. Results: The GeneChip analysis demonstrated that 132 up-regulated genes and 873 clown-regulated genes, such as growth factors, chemokines and transcription factors, were detected in MKN45 cells 3 h after stimulation of H. pylori. Among them, several genes, including bFGF, RANTES and MIP-2β, were previously unknown to be expressed in H. pylori-stimulated human gastric cells. Rebamipide reduced expression of 119 genes encoding cytokines, growth factors and their receptors and transcription factors. Conclusions: These findings suggest that rebamipide could inhibit inflammatory reactions and tumour progression by modifying H. pylori infection-induced gene expression in gastric epithelial cells.