AMPLIFICATION OF NITRIC-OXIDE SYNTHASE EXPRESSION BY NITRIC-OXIDE IN INTERLEUKIN 1-BETA-STIMULATED RAT MESANGIAL CELLS

被引:79
作者
MUHL, H [1 ]
PFEILSCHIFTER, J [1 ]
机构
[1] UNIV BASEL,BIOZENTRUM,DEPT PHARMACOL,CH-4056 BASEL,SWITZERLAND
关键词
NITRIC OXIDE; NITRIC OXIDE SYNTHASE; INTERLEUKIN; 1; MESANGIAL CELLS; NITRIC OXIDE DONORS;
D O I
10.1172/JCI117876
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Nitric oxide (NO) plays an important role in immunological reactions as a host defense mechanism against tumor cells and invasive microorganisms, but it may also damage healthy tissue, The excessive formation of NO in IL-1 beta-stimulated renal mesangial cells not only alters glomerular filtration, but it may also cause tissue injury and thus contribute to the pathogenesis of certain forms of glomerulonephritis, We report here that, although NO alone has no evident effect on NO synthase expression, it potently augments IL-1 beta-stimulated NO synthase expression in mesangial cells, NO donors such as sodium nitroprusside and S-nitroso-N-acetyl-D,L-penicillamine markedly increase IL-1 beta-induced NO synthase mRNA and protein levels as well as enzyme activity, Nuclear run-on experiments suggest that NO acts to increase IL-1 beta-induced NO synthase gene expression at the transcriptional level. Furthermore, inhibition of NO synthesis by different pharmacological approaches reduces IL-1 beta-induced NO synthase expression, thus suggesting that NO functions in a positive feedback loop that speeds up and strengthens its own biosynthesis. We suggest that this potent amplification mechanism forms the basis for the excessive formation df NO in acute and chronic inflammatory diseases.
引用
收藏
页码:1941 / 1946
页数:6
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