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Title :NF-kappaB 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
Issue Date :12-Feb-2009
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 dominant-negative 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.
URL :http://www.biomedcentral.com/1471-2180/9/36
Type Local :雑誌掲載論文
Publisher :BioMed Central Ltd.
URI :http://hdl.handle.net/20.500.12000/10318
Citation :BMC microbiology Vol.9 p.36
Appears in Collections:Peer-reviewed Journal Articles (Faculty of Medicine)

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