Insulin inhibits NFkappaB 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 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.
Aljada
A
A
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo and Kaleida Health, Buffalo, New York 14209, USA.
Ghanim
H
H
Saadeh
R
R
Dandona
P
P
D001011:Aorta / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*
D018932:Chemokine CCL2; D007328:Insulin; D016328:NF-kappa B