Macrophages stimulated with IFN-gamma activate NF-kappa B and induce MCP-1 gene expression in primary human endothelial cells.
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 interactions occurring in the process of cardiovascular diseases. The coculture of macrophages grown on filters 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 monocytes into the subendothelial space could affect redox-sensitive transcription factors and gene expression in the endothelium, thereby possibly leading to endothelial dysfunction.
Rimbach
G
G
Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California, USA.
Valacchi
G
G
Canali
R
R
Virgili
F
F
D000818:Animals; D001324:Autoantigens / Q000235:genetics*; D002478:Cells, Cultured; D018932:Chemokine CCL2; D018920:Coculture Techniques; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D017930:Genes, Reporter; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects*
D001324:Autoantigens; C111835:CCL2 protein, human; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D007371:Interferon-gamma; D004247:DNA