Insulin inhibits NF kappa B and MCP-1 expression in human aortic endothelial cells

In view of our recent demonstration that insulin inhibits the expression of intercellular adhesion molecule-1 (ICAM-1) and the fact that ICAM-1 expres sion is known to be modulated by nuclear factor-kappaB (NF kappaB), We have now investigated whether insulin inhibits intranuclear NF kappaB binding a ctivity. We have also investigated whether insulin inhibits the pro-inflamm atory chemokine, monocyte chemoattractant protein-1 (MCP-1), which attracts leucocytes to the inflamed sites and is also regulated by NF kappaB. insul in was incubated with cultured human aortic endothelial cells (HAEC) at 0, 100 and 1000 muU/mL. Intranuclear NF kappaB binding activity was suppressed by approximately 45 % at 100 muU/mL and by 60 % at 1000 muU/mL (p<0.05). M CP-1 mRNA expression was also suppressed by 47% at 100 <mu>U/mL and by 79 % at 1000 muU/mL (p<0.05). We conclude that insulin at physiologically relev ant concentrations exerts an inhibitory effect on the cardinal pro-inflamma tory transcription factor NF<kappa>B and the pro-inflammatory chemokine MCP -1; these effects suggest an anti-inflammatory and potential anti-atherogen ic affects of insulin.