NF-κB, inducible nitric oxide synthase and apoptosis by Helicobacter pylori infection

Abstract

Oxygen radicals are considered as an important regulator in the pathogenesis of Helicobacter pylori (H. pylori)-induced gastric ulceration and carcinogenesis. Inflammatory genes including inducible nitric oxide synthase (iNOS) may be regulated by oxidant-sensitive transcription factor, nuclear factor-κB (NF-κB). iNOS induction has been related to gastric apoptosis. We studied the role of NF-κB on iNOS expression and apoptosis in H. pylori-stimulated gastric epithelial AGS cells. AGS cells were treated with antisense oligonucleotide (AS ODN) for NF-κB subunit p50, an antioxidant enzyme catalase, an inhibitor of NF-κB activation pyrrolidine dithiocarbamate (PDTC), iNOS inhibitors NG-nitro-L-arginine-methyl ester (L-NAME) and 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT), a peroxynitrite donor SIN-1, and a nitric oxide donor NOC-18 in the presence or absence of H. pylori. H. pylori induced cytotocixity time- and dose-dependently, which occurred with induction in iNOS expression and nitrite production. SIN-1 and NOC-18 induced dose-dependent cytotoxicity in AGS cells. Catalase, PDTC, L-NAME, and AMT prevented H. pylori-induced cytotoxicity and apoptosis. It was related to their inhibition on iNOS expression and nitrite production. The cells treated with AS ODN had low levels of p50 and NF-κB and inhibited H. pylori-induced cytotoxicity, apoptosis, iNOS expression, and nitrite production. In conclusion, NF-κB plays a novel role in iNOS expression and apoptosis in H. pylori-infected gastric epithelial cells.