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

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

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

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 (Δ 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 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.

Original languageEnglish (US)
Pages (from-to)6134-6143
Number of pages10
JournalWorld Journal of Gastroenterology
Volume11
Issue number39
DOIs
StatePublished - Oct 21 2005

Keywords

  • Cag-pathogenicity islands
  • Cluster analysis
  • Helicobacter pylori
  • Signal transduction
  • cDNA microarray

ASJC Scopus subject areas

  • Gastroenterology

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  • Cite this

    Shibata, W., Hirata, Y., Yoshida, H., Otsuka, M., Hoshida, Y., Ogura, K., Maeda, S., Ohmae, T., Yanai, A., Mitsuno, Y., Seki, N., Kawabe, T., & Omata, M. (2005). NF-Κ and ERK-signaling pathways contribute to the gene expression induced by cag PAI-postive-Helicobacter pylori infection. World Journal of Gastroenterology, 11(39), 6134-6143. https://doi.org/10.3748/wjg.v11.i39.6134