Macrophages stimulated with IFN-gamma activate NF-kappa B and induce MCP-1 gene expression in primary human endothelial cells

Mol Cell Biol Res Commun. 2000 Apr;3(4):238-42. doi: 10.1006/mcbr.2000.0219.

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-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantigens / genetics*
  • Cells, Cultured
  • Chemokine CCL2*
  • Coculture Techniques
  • DNA / genetics
  • DNA / metabolism
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Genes, Reporter
  • Humans
  • Interferon-gamma / pharmacology*
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Mice
  • NF-kappa B / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / metabolism
  • Transcriptional Activation / drug effects*

Substances

  • Autoantigens
  • CCL2 protein, human
  • Ccl2 protein, mouse
  • Chemokine CCL2
  • NF-kappa B
  • RNA, Messenger
  • Reactive Oxygen Species
  • Interferon-gamma
  • DNA