title: NF-kappaB activation by Helicobacter pylori requires Akt-mediated phosphorylation of p65.
abstract: BACKGROUND
  The inflammatory response in Helicobacter pylori-infected gastric tissue is mediated by cag pathogenicity island (PAI)-dependent activation of nuclear factor-kappaB (NF-kappaB). Phosphatidylinositol 3-kinase (PI3K)/Akt signaling is known to play a role in NF-kappaB 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-kappaB 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-kappaB transactivation, as well as interleukin-8 expression. Furthermore, transfection with a dominant-negative Akt inhibited H. pylori-induced NF-kappaB transactivation. Transfection with small interference RNAs for p65 and Akt also inhibited H. pylori-induced interleukin-8 expression.
  
  
  CONCLUSIONS
  The results suggest that cag PAI-positive H. pylori activates Akt in gastric epithelial cells and this may contribute to H. pylori-mediated NF-kappaB activation associated with mucosal inflammation and carcinogenesis.
authors.affiliation: Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan. erichinai@yahoo.co.jp
authors.forename: Eriko
authors.initials: E
authors.lastname: Takeshima
authors.forename: Koh
authors.initials: K
authors.lastname: Tomimori
authors.forename: Hirochika
authors.initials: H
authors.lastname: Kawakami
authors.forename: Chie
authors.initials: C
authors.lastname: Ishikawa
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sawada
authors.forename: Mariko
authors.initials: M
authors.lastname: Tomita
authors.forename: Masachika
authors.initials: M
authors.lastname: Senba
authors.forename: Fukunori
authors.initials: F
authors.lastname: Kinjo
authors.forename: Hitomi
authors.initials: H
authors.lastname: Mimuro
authors.forename: Chihiro
authors.initials: C
authors.lastname: Sasakawa
authors.forename: Jiro
authors.initials: J
authors.lastname: Fujita
authors.forename: Naoki
authors.initials: N
authors.lastname: Mori
mesh_terms: D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology; D005786:Gene Expression Regulation; D044404:Genomic Islands; D016481:Helicobacter Infections / Q000378:metabolism; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D016328:NF-kappa B / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: D016209:Interleukin-8; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051996:Transcription Factor RelA