NF-kappaB activation by Helicobacter pylori requires Akt-mediated phosphorylation of p65.
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.
Takeshima
Eriko
E
Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan. erichinai@yahoo.co.jp
Tomimori
Koh
K
Kawakami
Hirochika
H
Ishikawa
Chie
C
Sawada
Shigeki
S
Tomita
Mariko
M
Senba
Masachika
M
Kinjo
Fukunori
F
Mimuro
Hitomi
H
Sasakawa
Chihiro
C
Fujita
Jiro
J
Mori
Naoki
N
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*
D016209:Interleukin-8; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051996:Transcription Factor RelA