Helicobacter pylori induces antiapoptosis through buclear factor-kappaB activation.
Although Helicobacter pylori is classified as a definite carcinogen, the mechanism underlying gastric carcinogenesis is not yet clear. We previously have shown that H. pylori activates an antiapoptotic gene, the cellular inhibitor of apoptosis protein 2 (c-IAP2), the underlying mechanism of which was investigated in the present study. cDNA array and real-time PCR analyses indicated that H. pylori showed a stimulatory effect on the expression of c-IAP2. Isogenic mutant strains with impaired cag pathogenicity island (cagPAI) expression showed weaker induction. Analyses that used the in situ terminal deoxynucleotide transferase-mediated dUTP nick end-labeling method indicated suppression of antiapoptosis by the antisense c-IAP2 oligonucleotide. Reporter assays with deletion and mutation constructs for the c-IAP2 promoter showed that nuclear factor-kappaB (NF-kappaB) binding sites are indispensable for transactivation. Super-repressor IkappaBalpha or NF-kappaB inhibitor reduced c-IAP2 transactivation by H. pylori, and exogenous expression of c-IAP2 inhibited apoptosis seen with H. pylori. In conclusion, H. pylori induces antiapoptosis through c-IAP2 transactivation following cagPAI-dependent NF-kappaB activation. The interaction of these stimuli may play a role in gastric carcinogenesis.
Yanai
Ayako
A
Department of Gastroenterology, Faculty of Medicine, University of Tokyo, Tokyo 113-8655, Japan. ayanai-gi@umin.ac.jp.
Hirata
Yoshihiro
Y
Mitsuno
Yuzo
Y
Maeda
Shin
S
Shibata
Wataru
W
Akanuma
Masao
M
Yoshida
Haruhiko
H
Kawabe
Takao
T
Omata
Masao
M
D017209:Apoptosis; D045744:Cell Line, Tumor; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics; D013274:Stomach Neoplasms / Q000473:pathology; D015533:Transcriptional Activation
D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; D011506:Proteins