NF-κB activation by <it>Helicobacter pylori </it>requires Akt-mediated phosphorylation of p65

• Main Authors: Tomita Mariko, Sawada Shigeki, Ishikawa Chie, Kawakami Hirochika, Tomimori Koh, Takeshima Eriko, Senba Masachika, Kinjo Fukunori, Mimuro Hitomi, Sasakawa Chihiro, Fujita Jiro, Mori Naoki
• Format: Article
• Language: English
• Published: BMC 2009-02-01
• Series: BMC Microbiology
• Online Access: http://www.biomedcentral.com/1471-2180/9/36

<p>Abstract</p> <p>Background</p> <p>The inflammatory response in <it>Helicobacter pylori</it>-infected gastric tissue is mediated by <it>cag </it>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 <it>H. pylori </it>and PI3K/Akt signaling in gastric epithelial cells. We examined whether <it>H. pylori </it>activates Akt in gastric epithelial cells, the role of <it>cag </it>PAI in this process and the role of Akt in regulating <it>H. pylori</it>-induced NF-κB activation.</p> <p>Results</p> <p>Phosphorylated Akt was detected in epithelial cells of <it>H. pylori</it>-positive gastric tissues. Although Akt was activated in MKN45 and AGS cells by coculture with <it>cag </it>PAI-positive <it>H. pylori </it>strains, a <it>cag </it>PAI-negative mutant showed no activation of Akt. <it>H. pylori </it>also induced p65 phosphorylation. PI3K inhibitor suppressed <it>H. pylori</it>-induced p65 phosphorylation and NF-κB transactivation, as well as interleukin-8 expression. Furthermore, transfection with a dominant-negative Akt inhibited <it>H. pylori</it>-induced NF-κB transactivation. Transfection with small interference RNAs for p65 and Akt also inhibited <it>H. pylori</it>-induced interleukin-8 expression.</p> <p>Conclusion</p> <p>The results suggest that <it>cag </it>PAI-positive <it>H. pylori </it>activates Akt in gastric epithelial cells and this may contribute to <it>H. pylori</it>-mediated NF-κB activation associated with mucosal inflammation and carcinogenesis.</p>