Macrophages Stimulated with IFN-#gamma# Activate NF-#kappa#B and Induce MCP-1 Gene Expression in Primary Human Endothelial Cells

摘要

A novel coculture model was established to study the effects of reactive oxygen (ROS) and reactive nitrogen species (RNS) generated by RAW 264.7 macrophages on NF-#kappa#B activation and monocyte chemoattractant protein (MCP-1) gene expression in primary human endothelial cells (HUVEC).This model simulates free radical-mediated interctions occurring in the process of cardiovascular diseases.The coculture of macrophages grown on filers and stimulated by IFN-#gamma#-induced a pro-oxidant environment and resulted in increased DNA binding and NF-#kappa#B transactivation in HUVEC.Activation of NF-#kappa#B in endothelial cells was accompanied by an evident increase in the expression of the mRNA encoding for the MCP-1 protein,which stimulates the recruitment of monocytes into the arterial wall.Present data suggest that the influx of stimulated moncytes into the subendothelial space could affect redox-sensitive transcription factors and gene expression in the endothelium,thereby possibly leading to endothelial dysfunction.