Nitric oxide-induced IL-8 expression is mediated by NF-kappaB and AP-1 in gastric epithelial AGS cells.
Inducible nitric oxide synthase (iNOS) and interleukin-8 (IL-8) mediate gastric inflammation. Nitric oxide (NO) produced by iNOS may activate oxidant-sensitive transcription factors. There are the binding sites for NF-kappaB, AP-1, and C/EBP (CCAAT/enhancer binding protein) in the promoter regions of IL-8 gene. The present study aims to investigate whether NO donors, SIN-1 and NOC-18, activate oxidant-sensitive transcription factors NF-kappaB and AP-1 as well as C/EBP to induce IL-8 expression in gastric epithelial AGS cells. Gastric epithelial AGS cells were treated with NO donors, SIN-1 and NOC-18. mRNA expression and protein level of IL-8 in the medium were determined. Nitrite level in the medium and DNA binding activities of NF-kappaB, AP-1, and C/EBP were assessed. NO donors induced the increase in the levels of IL-8 and nitrite in the medium as well as mRNA expression of IL-8 in AGS cells time-dependently. The induction of IL-8 by NO donors was accompanied with the activation of NF-kappaB and AP-1 but not C/EBP in AGS cells.


CONCLUSIONS
Large amount of NO, which may be produced by iNOS, may induce the activation of NF-kappaB and AP-1 and the expression of IL-8 in gastric epithelial cells.
Seo
J Y
JY
Department of Food and Nutrition, Brain Korea 21 Project, College of Human Ecology, Yonsei University, Seoul, Korea.
Yu
J-H
JH
Lim
J W
JW
Mukaida
N
N
Kim
H
H
D000897:Anti-Ulcer Agents / Q000494:pharmacology; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D004847:Epithelial Cells; D005753:Gastric Mucosa / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000032:analysis / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D000897:Anti-Ulcer Agents; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D016209:Interleukin-8; D016328:NF-kappa B; C093285:NOC 18; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine