NF-κB and ERK-signaling pathways contribute to the gene expression induced by cag PAI-positive-Helicobacter pylori infection

查看全文 作　　者：Wataru [1]Shibata;Yoshihiro [1]Hirata;Haruhiko [1]Yoshida;Motoyuki [1]Otsuka;Yujin [1]Hoshida;Keiji [1]Ogura;Shin [1]Maeda;Tomoya [1]Ohmae;Ayako [1]Yanai;Yuzo [1]Mitsuno;Naohiko [2]Seki;Takao [1]Kawabe;Masao [1]Omata

机构地区：[1]Department of Gastroenterology Graduate School of Medicine,University of Tokyo,Japan;[2]Department of Functional Genomics Graduate School of Medicine,University of Chiba,Japan

出　　处：《World Journal of Gastroenterology》索引2005年第11卷第39期,共10页

基　　金：Supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sport, and Culture of Japan 摘　　要：AIM: To elucidate the sequential gene expression profile in AGS cells co-cultured with wild-type Hellcobacter pylori (Hpylon) as a model of H pylori-infected gastric epithelium, and to further examine the contribution of cag-pathogenicity islands (cagPAI)-coding type Ⅳ secretion system and the two pathways, nuclear factor kappa B (NF-κB) and extracellular signal-regulated kinases (ERK) on wild-type H pylori-induced gene expression. METHODS: Gene expression profiles induced by H pylori were evaluated in AGS gastric epithelial cells using cDNA microarray, which were present in the 4 600 independent clones picked up from the human gastric tissue. We also analyzed the contribution of NF-κB and ERK signaling on H pylori-induced gene expression by using inhibitors of specific signal pathways. The isogenic mutant with disrupted capE (△cagE) was used to elucidate the role of capPAI-encoding type Ⅳ secretion system in the gene expression profile. RESULTS: According to the expression profile, the genes were classified into four clusters. Among them, the clusters characterized by continuous upregulation were most conspicuous, and it contained many signal transducer activity-associated genes. The role of cagPAI on cultured cells was also investigated using isogenic mutant cagE, which carries non-functional cagPAI. Then the upregulation of more than 80% of the induced genes (476/566) was found to depend on cagPAI. Signal transducer pathway through NF-κB or ERK are the major pathways which are known to be activated by cagPAI-positive H pylori. The role of these pathways in the whole signal activation by cagPAI- positive H pylori was analyzed. The specific inhibitors against NF-κB or ERK pathway blocked the activation of gene expression in 65% (367/566) or 76% (429/566) of the genes whose activation appealed to depend on cagPAI. CONCLUSION: These results suggest that more than half of the genes induced by cagPAI-positive H pylori depend on NF-κB and ERK signaling activation, and these pathways may play a role in the gene expression induced by host-bacterial interaction which may associate with H pylori-related gastro-duodenal diseases. 关键词：NF-ΚB 信号路径基因表达十二指肠疾病信号转导

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NF-κB and ERK-signaling pathways contribute to the gene expression induced by cag PAI-positive-Helicobacter pylori infection

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