Linoleic acid induces MCP-1 gene expression in human microvascular endothelial cells through an oxidative mechanism

Linoleic acid is a dietary fatty acid that appears to play an important role in activation of the vascular endothelium under a variety of pathological conditions, including development of atherosclerosis or cancer metastasis. Evidence indicates that inflammatory responses may be an underlying cause of endothelial cell pathology induced by linoleic acid. However, the profile of inflammatory mediators and the potential mechanisms involved in inflammatory reactions stimulated by the exposure to linoleic acid are not fully understood. The present study focused on the mechanisms of linoleic acid-induced expression of monocyte chemoattractant protein-1 (MCP-1) gene in human microvascular endothelial cells (HMEC-1). Treatment of HMEC-1 with increasing doses of linoleic acid markedly activated an oxidative stress-responsive transcription factor, nuclear factor-kappaB (NF-kappaB). In addition, exposure to linoleic acid induced a time- and concentration-dependent overexpression of the MCP-1 gene. Increased MCP-1 mRNA levels were observed in HMEC-1 treated with linoleic acid at doses as low as 10 &mgr;M. Linoleic acid-induced overexpression of the MCP-1 gene was associated with a significant elevation of MCP-1 protein levels. Most importantly, preexposure of HMEC-1 to antioxidants, such as pyrrolidine dithiocarbamate (PDTC) or N-acetylcysteine (NAC), attenuated linoleic acid-induced MCP-1 mRNA expression. The obtained results indicate that linoleic acid triggers MCP-1 gene expression in human microvascular endothelial cells through oxidative stress/redox-related mechanisms.