Submitted on November 25, 2002
Accepted on June 24, 2003
Helicobacter pylori infection activates the NF-
B signaling pathway to induce iNOS and protect human gastric epithelial cells from apoptosis
JUNG MOGG KIM1, JOO SUNG KIM2, HYUN CHAE JUNG2*, YU-KYOUNG OH3, HEE-YOUNG CHUNG1, CHUL-HOON LEE4, and IN SUNG SONG2
1 Department of Microbiology and Institute of Biomedical Science, Hanyang University College of Medicine, Seoul, Korea, Republic of
2 Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea, Republic of
3 Department of Microbiology, Pochon CHA University College of Medicine, Kyunggi-do, Korea, Republic of
4 Department of Medical Genetics, Hanyang University College of Medicine, Seoul, Korea, Republic of
* To whom correspondence should be addressed. E-mail: hyunchae{at}plaza.snu.ac.kr.
Helicobacter pylori infection induces apoptosis and inducible nitric oxide synthase (iNOS) expression in gastric epithelial cells. In this study, we investigated the effects of NF-
B activation and iNOS expression on apoptosis in H. pylori-infected gastric epithelial cells. The suppression of NF-B significantly increased caspase-3 activity and apoptosis in H. pylori-infected MKN-45 and Hs746T gastric epithelial cell lines as well as primary gastric epithelial cells. An NF-B signaling pathway via NF-B-inducing kinase (NIK) and IB kinase (IKK)
activation was found to be involved in the inhibition of apoptosis in H. pylori-infected gastric epithelial cells. In gastric epithelial cells transfected with retrovirus containing IB
superrepressor, iNOS mRNA and protein levels were reduced, indicating that H. pylori infection induced the expression of iNOS by activating NF-B. Moreover, an NO donor, S-nitroso-N-acetylpenicillamine (100 µM), decreased caspase-3 activity and apoptosis in NF-B-suppressed cells infected with H. pylori. These results suggest that NF-B activation may play a role in protecting gastric epithelial cells from H. pylori-induced apoptosis by up-regulating endogenous iNOS.
