Nitric oxide-induced IL-8 expression is mediated by NF-kappaB and AP-1 in gastric epithelial AGS cells.

Abstract

UNLABELLED: 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. CONCLUSION: 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.