title: Nitric oxide modulates the expression of monocyte chemoattractant protein 1 in cultured human endothelial cells.
abstract: The recruitment of monocytes into the arterial wall is one of the earliest events in the pathogenesis of atherosclerosis. Since monocyte chemoattractant protein 1 (MCP-1) plays a key role in the subendothelial recruitment of monocytes, we tested whether nitric oxide (NO) modulates the expression of MCP-1 in cultured human endothelial cells. Inhibition of basal NO production by NG-nitro-L-arginine (L-NAG) upregulates endothelial MCP-1 mRNA expression (250 +/- 20%) and protein secretion. Exogenous addition of NO dose-dependently decreased MCP-1 mRNA expression and secretion. Changes in MCP-1 mRNA expression and protein secretion were paralleled by corresponding changes in chemotactic activity of cell-conditioned media for monocytes. An MCP-1 antibody reduced monocyte chemotactic activity by 85% and completely abolished the increased monocyte chemotactic activity induced by the inhibition of NO production. Elevation of endothelial cGMP levels had no significant effect on MCP-1 mRNA expression. Inhibition of basal endothelial NO production by L-NAG increased binding activity of a nuclear factor kappa B (NF-kappa B)-like transcriptional regulatory factor, whereas exogenous addition of NO decreased NF-kappa B-like binding activity during stimulation with tumor necrosis factor-alpha. Thus, NO modulates MCP-1 expression and monocyte chemotactic activity secreted by human umbilical vein endothelial cells (HUVECs) in culture. The activation of NF-kappa B-like transcriptional regulatory proteins by inhibition of NO suggests a molecular link between an oxidant-sensitive transcriptional regulatory mechanism and NO synthesis in HUVECs.
authors.affiliation: Department of Internal Medicine IV, University of Frankfurt, Germany.
authors.forename: A M
authors.initials: AM
authors.lastname: Zeiher
authors.forename: B
authors.initials: B
authors.lastname: Fisslthaler
authors.forename: B
authors.initials: B
authors.lastname: Schray-Utz
authors.forename: R
authors.initials: R
authors.lastname: Busse
mesh_terms: D001161:Arteriosclerosis / Q000209:etiology; D001665:Binding Sites; D015152:Blotting, Northern; D002478:Cells, Cultured; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000235:genetics* / Q000378:metabolism; D002633:Chemotaxis; D016207:Cytokines / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology*; D014158:Transcription, Genetic; D014471:Umbilical Veins; D015854:Up-Regulation
chemical_list: D018932:Chemokine CCL2; D002630:Chemotactic Factors; D016207:Cytokines; D004268:DNA-Binding Proteins; D009569:Nitric Oxide