Nitric oxide regulates interleukin-8 gene expression in activated endothelium by inhibiting NF-κB binding to DNA:: effects on endothelial function

被引:33
作者
Fowler, AA
Fisher, BJ
Sweeney, LB
Wallace, TJ
Natarajan, R
Ghosh, SS
Ghosh, S
机构
[1] Virginia Commonwealth Univ, Sch Med, Div Pulm & Crit Care Med, Dept Internal Med, Richmond, VA 23298 USA
[2] Virginia Commonwealth Univ, Sch Med, Dept Biochem & Mol Biophys, Richmond, VA 23298 USA
来源
BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE | 1999年 / 77卷 / 03期
关键词
interleukin-8; nuclear factor kappa B; transendothelial migration; nitric oxide;
D O I
10.1139/bcb-77-3-201
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Nuclear factor-kappa B (NF-kappa B) binds to nucleotide sequences between -80 and -70 bp upstream of the transcriptional start site in the interleukin-8 (IL-8) promoter and is crucial for transcription of the IL-8 gene, We showed that exogenous nitric oxide in the form of a-nitric oxide donor significantly reduced IL-8 mRNA in cytokine-activated ECV304. Similarly, nitric oxide significantly:reduced migration of polymorphonuclear neutrophils through cytokine-activated ECV304 monolayers, an IL-8-dependent process. Using a luciferase reporter construct containing the NF-kappa B site of the IL-8 gene, we showed that exposing cytokine-activated ECV304 to exogenous nitric oxide resulted in significant reduction of NF-kappa B binding. Follow-up studies using a luciferase reporter construct possessing a mutated NF-kappa B site confirmed that the luciferase activity observed in the NF-kappa B reporter resulted from NF-kappa B binding. These studies demonstrate that nitric oxide, supplied exogenously into reactions containing activated endothelium, downregulates pro-inflammatory activity, such as the secretion of chemokines, and functional activity, such as transendothelial migration of neutrophils.
引用
收藏
页码:201 / 208
页数:8
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