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

• Published in: 世界胃肠病学杂志（英文版） Vol. 11; no. 39; pp. 6134 - 6143
• Main Authors: Wataru Shibata, Yoshihiro Hirata, Haruhiko Yoshida, Motoyuki Otsuka, Yujin Hoshida, Keiji Ogura, Shin Maeda, Tomoya Ohmae, Ayako Yanai, Yuzo Mitsuno, Naohiko Seki, Takao Kawabe, Masao Omata
• Format: Journal Article
• Language: English
• Published: Department of Gastroenterology,Graduate School of Medicine,University of Tokyo,Japan%Department of Functional Genomics,Graduate School of Medicine,University of Chiba,Japan 21.10.2005
• Subjects: Helicobacter pylori,Cag-pathogenicity islands; Signal transduction; cDNA microarray,Cluster analysis
• ISSN: 1007-9327
• DOI: 10.3748/wjg.v11.i39.6134

R3; AIM: To elucidate the sequential gene expression profile in AGS cells co-cultured with wild-type Helicobacter pylori(H pylori) 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 cagE (△cagE) was used to elucidate the role of cagPAI-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 cagPAIpositive 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 hostbacterial interaction which may associate with H pylorirelated gastro-duodenal diseases.