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- Title
NF-κB activation by Helicobacter pylori requires Akt-mediated phosphorylation of p65.
- Authors
Takeshima, Eriko; Tomimori, Koh; Kawakami, Hirochika; Ishikawa, Chie; Sawada, Shigeki; Tomita, Mariko; Senba, Masachika; Kinjo, Fukunori; Mimuro, Hitomi; Sasakawa, Chihiro; Fujita, Jiro; Mori, Naoki
- Abstract
Background: The inflammatory response in Helicobacter pylori-infected gastric tissue is mediated by cag pathogenicity island (PAI)-dependent activation of nuclear factor-κB (NF-κB). Phosphatidylinositol 3-kinase (PI3K)/Akt signaling is known to play a role in NF-κB activation, but little information is available on the relationship between H. pylori and PI3K/Akt signaling in gastric epithelial cells. We examined whether H. pylori activates Akt in gastric epithelial cells, the role of cag PAI in this process and the role of Akt in regulating H. pylori-induced NF-κB activation. Results: Phosphorylated Akt was detected in epithelial cells of H. pylori-positive gastric tissues. Although Akt was activated in MKN45 and AGS cells by coculture with cag PAI-positive H. pylori strains, a cag PAI-negative mutant showed no activation of Akt. H. pylori also induced p65 phosphorylation. PI3K inhibitor suppressed H. pylori-induced p65 phosphorylation and NF-κB transactivation, as well as interleukin-8 expression. Furthermore, transfection with a dominantnegative Akt inhibited H. pylori-induced NF-κB transactivation. Transfection with small interference RNAs for p65 and Akt also inhibited H. pylori-induced interleukin-8 expression. Conclusion: The results suggest that cag PAI-positive H. pylori activates Akt in gastric epithelial cells and this may contribute to H. pylori-mediated NF-κB activation associated with mucosal inflammation and carcinogenesis.
- Subjects
HELICOBACTER pylori; PHOSPHORYLATION; NF-kappa B; DNA-binding proteins; TRANSCRIPTION factors
- Publication
BMC Microbiology, 2009, Vol 9, p1
- ISSN
1471-2180
- Publication type
Article
- DOI
10.1186/1471-2180-9-36