Helicobacter pylori infection activates NF-kappaB signaling pathway to induce iNOS and protect human gastric epithelial cells from apoptosis.
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-kappaB activation and iNOS expression on apoptosis in H. pylori-infected gastric epithelial cells. The suppression of NF-kappaB 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-kappaB signaling pathway via NF-kappaB-inducing kinase and IkappaB kinase-beta 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 IkappaBalpha superrepressor, iNOS mRNA and protein levels were reduced, indicating that H. pylori infection induced the expression of iNOS by activating NF-kappaB. Moreover, a NO donor, S-nitroso-N-acetylpenicillamine (100 microM), decreased caspase-3 activity and apoptosis in NF-kappaB-suppressed cells infected with H. pylori. These results suggest that NF-kappaB activation may play a role in protecting gastric epithelial cells from H. pylori-induced apoptosis by upregulating endogenous iNOS.
Kim
Jung Mogg
JM
Department of Microbiology and Institute of Biomedical Science, Hanyang University College of Medicine, Seoul, Korea.
Kim
Joo Sung
JS
Jung
Hyun Chae
HC
Oh
Yu-Kyoung
YK
Chung
Hee-Young
HY
Lee
Chul-Hoon
CH
Song
In Sung
IS
D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation; D004790:Enzyme Induction; D004847:Epithelial Cells; D005753:Gastric Mucosa / Q000503:physiopathology*; D016481:Helicobacter Infections / Q000378:metabolism / Q000503:physiopathology*; D016480:Helicobacter pylori; D006801:Humans; D051550:I-kappa B Kinase; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D000097782:NF-kappaB-Inducing Kinase
D053148:Caspase 3; D020169:Caspases; D051550:I-kappa B Kinase; D016328:NF-kappa B; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D017346:Protein Serine-Threonine Kinases; D000097782:NF-kappaB-Inducing Kinase; C496319:NOS2 protein, human; C496559:CHUK protein, human; C496560:IKBKB protein, human; C496565:IKBKE protein, human; C505407:CASP3 protein, human