Yoshida N, Ishikawa T, Ichiishi E, Yoshida Y, Hanashiro K, Kuchide M, Uchiyama K, Kokura S, Ichikawa H, Naito Y, Yamamura Y, Okanoue T, Yoshikawa T
Molecular Gastroenterology and Hepatology and Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Aliment Pharmacol Ther. 2003 Jul;18 Suppl 1:63-75. doi: 10.1046/j.1365-2036.18.s1.7.x.
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).
In this study, we investigated the effects of rebamipide on gene expression in H. pylori-stimulated epithelial cells using DNA chip.
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.
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.
These findings suggest that rebamipide could inhibit inflammatory reactions and tumour progression by modifying H. pylori infection-induced gene expression in gastric epithelial cells.
近期研究表明，幽门螺杆菌会影响宿主细胞内的信号转导，从而导致转录因子的激活及促炎细胞因子的诱导。另一方面，瑞巴派特作为一种抗胃炎和抗溃疡药物，可清除活性氧，并通过减弱核因子-κB（NF-κB）的激活来降低幽门螺杆菌刺激诱导的胃上皮细胞中白细胞介素-8（IL-8）的表达。
在本研究中，我们使用DNA芯片研究了瑞巴派特对幽门螺杆菌刺激的上皮细胞基因表达的影响。
幽门螺杆菌水提取物（HPE）由幽门螺杆菌标准菌株NCTC11637制备。在用或不用瑞巴派特对人胃癌细胞系MKN45细胞进行HPE刺激3小时后，提取总RNA，并使用基因芯片和人类6800探针阵列观察基因表达谱的差异。
基因芯片分析表明，在幽门螺杆菌刺激后3小时的MKN45细胞中检测到132个上调基因和873个下调基因，如生长因子、趋化因子和转录因子。其中，包括碱性成纤维细胞生长因子（bFGF）、调节激活正常T细胞表达和分泌因子（RANTES）和巨噬细胞炎性蛋白-2β（MIP-2β）在内的几个基因，此前未知在幽门螺杆菌刺激的人胃细胞中表达。瑞巴派特降低了119个编码细胞因子、生长因子及其受体和转录因子的基因的表达。
这些发现表明，瑞巴派特可通过改变幽门螺杆菌感染诱导的胃上皮细胞基因表达来抑制炎症反应和肿瘤进展。
