NF-kappaB, inducible nitric oxide synthase and apoptosis by Helicobacter pylori infection.
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-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. pylori-stimulated gastric epithelial AGS cells. AGS cells were treated with antisense oligonucleotide (AS ODN) for NF-kappaB subunit p50, an antioxidant enzyme catalase, an inhibitor of NF-kappaB activation pyrrolidine dithiocarbamate (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 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-kappaB and inhibited 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.
Lim
J W
JW
Department of Pharmacology and Institute of Gastroenterology, Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul 120-752, South Korea.
Kim
H
H
Kim
K H
KH
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D002374:Catalase / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004790:Enzyme Induction; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000382:microbiology* / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D016481:Helicobacter Infections / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D016480:Helicobacter pylori; D006801:Humans; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D009603:Nitroso Compounds / Q000494:pharmacology; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D011837:Radiation-Protective Agents / Q000494:pharmacology; D013843:Thiazines / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology
D000975:Antioxidants; D016328:NF-kappa B; C093285:NOC 18; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D020319:Oligodeoxyribonucleotides, Antisense; D011759:Pyrrolidines; D011837:Radiation-Protective Agents; D013843:Thiazines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; C018450:2-amino-5,6-dihydro-4H-1,3-thiazine; C002385:linsidomine; D008981:Molsidomine; D002374:Catalase; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D019331:NG-Nitroarginine Methyl Ester