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

Oxygen radicals are considered as an important regulator in the pathogenesi s of Helicobacter pylori (H. pylori)-induced gastric ulceration and carcino genesis. Inflammatory genes including inducible nitric oxide synthase (iNOS ) may be regulated by oxidant-sensitive transcription factor, nuclear facto r-kappaB (NF-kappaB). iNOS induction has been related to gastric apoptosis. We studied the role of NF-kappaB on iNOS expression and apoptosis in H. py lori-stimulated gastric epithelial AGS cells. AGS cells were treated with a ntisense oligonucleotide (AS ODN) for NF-kappaB subunit p50, an antioxidant enzyme catalase, an inhibitor of NF-kappaB activation pyrrolidine dithioca rbamate (PDTC), iNOS inhibitors N-G-nitro-L-arginine-methyl ester (L-NAME) and 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT), a peroxynitrite don or 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 oc curred 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 wa s related to their inhibition on iNOS expression and nitrite production. Th e cells treated with AS ODN had low levels of p50 and NF-kappaB and inhibit ed H. pylori-induced cytotoxicity, apoptosis, iNOS expression, and nitrite production. In conclusion, NF-kappaB plays a novel role in iNOS expression and apoptosis in H. pylori-infected gastric epithelial cells. (C) 2001 Else vier Science Inc.