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Insulin Inhibits NFB and MCP-1 Expression in Human Aortic Endothelial Cells

Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo and Kaleida Health, Buffalo, New York 14209

Abstract

In view of our recent demonstration that insulin inhibits the expression of intercellular adhesion molecule-1 (ICAM-1) and the fact that ICAM-1 expression is known to be modulated by nuclear factor-B (NFB), we have now investigated whether insulin inhibits intranuclear NFB binding activity. We have also investigated whether insulin inhibits the pro-inflammatory chemokine, monocyte chemoattractant protein-1 (MCP-1), which attracts leucocytes to the inflamed sites and is also regulated by NFB. Insulin was incubated with cultured human aortic endothelial cells (HAEC) at 0, 100 and 1000 µU/mL. Intranuclear NFB binding activity was suppressed by approximately 45% at 100 µU/mL and by 60% at 1000 µU/mL (p < 0.05). MCP-1 mRNA expression was also suppressed by 47% at 100 µU/mL and by 79% at 1000 µU/mL (p < 0.05). We conclude that insulin at physiologically relevant concentrations exerts an inhibitory effect on the cardinal pro-inflammatory transcription factor NFB and the pro-inflammatory chemokine MCP-1; these effects suggest an anti-inflammatory and potential anti-atherogenic effects of insulin.

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