Nitric Oxide Inhibits Macrophage-Colony Stimulating Factor Gene Transcription in Vascular Endothelial Cells
Open Access
- 1 July 1995
- journal article
- Published by Elsevier BV in Journal of Biological Chemistry
- Vol. 270 (28), 17050-17055
- https://doi.org/10.1074/jbc.270.28.17050
Abstract
Macrophage-colony stimulating factor (M-CSF) contributes to atherogenesis by regulating macrophage-derived foam cells in atherosclerotic lesions. Here we report that nitric oxide (NO) inhibits the expression of M-CSF in human vascular endothelial cells independent of guanylyl cyclase activation. The induction of M-CSF mRNA expression by either oxidized low density lipoprotein (ox-LDL) or tumor necrosis factor-α (TNFα) was attenuated by NO donors, S-nitrosoglutathione (GSNO), sodium nitroprusside (SNP), and 3-morpholinosydnonimine, but not by cGMP analogues, glutathione, or nitrite. Inhibition of endogenous NO production by N-monomethyl-L-arginine (L-NMA) also increased M-CSF expression in control and TNFα-stimulated cells. Nuclear run-on assays and transfection studies using M-CSF promoter constructs linked to chloramphenicol acetyltransferase reporter gene indicated that NO repressed M-CSF gene transcription through nuclear factor-κB (NF-κB). Electrophoretic mobility shift assays demonstrated that activation of NF-κB by L-NMA, ox-LDL, and TNFα was attenuated by GSNO and SNP, but not by glutathione or cGMP analogues. Since the induction of M-CSF expression depends upon NF-κB activation, the ability of NO to inhibit NF-κB activation and M-CSF expression may contribute to some of NO's antiatherogenic properties.Keywords
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