Insulin inhibits NFkappaB and MCP-1 expression in human aortic endothelial cells

J Clin Endocrinol Metab. 2001 Jan;86(1):450-3. doi: 10.1210/jcem.86.1.7278.

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-kappaB (NFkappaB), we have now investigated whether insulin inhibits intranuclear NFkappaB 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 NFkappaB. Insulin was incubated with cultured human aortic endothelial cells (HAEC) at 0, 100 and 1000 microU/mL. Intranuclear NFkappaB binding activity was suppressed by approximately 45% at 100 microU/mL and by 60% at 1000 microU/mL (p < 0.05). MCP-1 mRNA expression was also suppressed by 47% at 100 microU/mL and by 79% at 1000 microU/mL (p < 0.05). We conclude that insulin at physiologically relevant concentrations exerts an inhibitory effect on the cardinal pro-inflammatory transcription factor NFkappaB and the pro-inflammatory chemokine MCP-1; these effects suggest an anti-inflammatory and potential anti-atherogenic effects of insulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aorta / cytology
  • Aorta / metabolism*
  • Cells, Cultured
  • Chemokine CCL2 / antagonists & inhibitors*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Humans
  • Insulin / pharmacology*
  • NF-kappa B / antagonists & inhibitors*

Substances

  • Chemokine CCL2
  • Insulin
  • NF-kappa B