The effect of rebamipide on Helicobacter pylori extract-mediated changes of gene expression in gastric epithelial cells.
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-kappaB (NF-kappaB).


OBJECTIVE
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 down-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-2beta, 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.
Yoshida
N
N
Molecular Gastroenterology and Hepatology and Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. nyoshida@koto-m.ac.jp
Ishikawa
T
T
Ichiishi
E
E
Yoshida
Y
Y
Hanashiro
K
K
Kuchide
M
M
Uchiyama
K
K
Kokura
S
S
Ichikawa
H
H
Naito
Y
Y
Yamamura
Y
Y
Okanoue
T
T
Yoshikawa
T
T
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D018946:Chemokine CCL5 / Q000235:genetics; D054426:Chemokine CXCL2; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D005753:Gastric Mucosa / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D015846:Monokines / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D015363:Quinolones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism / Q000382:microbiology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000897:Anti-Ulcer Agents; D018946:Chemokine CCL5; D054426:Chemokine CXCL2; D015846:Monokines; D016328:NF-kappa B; D015363:Quinolones; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; C052785:rebamipide; D000409:Alanine