Macrophages Stimulated with IFN-γ Activate NF-κB and Induce MCP-1 Gene Expression in Primary Human Endothelial Cells

Abstract 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-κB activation and monocyte chemoattractant protein (MCP-1) gene expression in primary human endothelial cells (HUVEC). This model simulates free radical-mediated interactions occurring in the process of cardiovascular diseases. The coculture of macrophages grown on filters and stimulated by IFN-γ-induced a pro-oxidant environment and resulted in increased DNA binding and NF-κB transactivation in HUVEC. Activation of NF-κB 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 monocytes into the subendothelial space could affect redox-sensitive transcription factors and gene expression in the endothelium, thereby possibly leading to endothelial dysfunction.