Insulin inhibits the pro-inflammatory transcription factor early growth response gene-1 (Egr)-1 expression in mononuclear cells (MNC) and reduces plasma tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) concentrations

We have recently demonstrated that an infusion of a low dose of insulin reduces the intranuclear NF-κB (a pro-inflammatory transcription factor) content in MNC while also reducing the plasma concentration of NFκB dependent pro-inflammatory cytokines and adhesion molecules. We have now tested the effect of insulin on the pro-inflammatory transcription factor, early growth response-1 (Egr-1) and plasma concentration of tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1), two major proteins whose expression is modulated by Egr-1. Insulin was infused at the rate of 2 IU/h in 5 % dextrose (100 mL/h) and KCl (8 mmol/h) for 4 h in the fasting state in ten obese subjects. Blood samples were obtained at 0, 2, 4 and 6 h. MNC were isolated and their total homogenates and nuclear fractions were prepared and Egr-1 was measured by electrophoretic mobility shift assay (EMSA). Plasma TF and PAI-1 were assayed by ELISA. There was a significant fall in Egr-1 at 2 (66 ± 14% of basal level) and 4h (47 ± 17 % of the basal level; P<0.01). PAI-1 levels (basal = 100 %) decreased significantly after insulin infusion at 2 h (57 ± 6.7 % of the basal level) and at 4 h (58 ± 8.3 % of the basal level; P<0.001). Plasma TF levels (basal = 100 %) decreased to 76 ± 7.7 % of the basal level at 2h and to 85 ± 10.4 % of the basal level at 4 h (P<0.05). Thus, insulin reduces intranuclear Egr-1 and the expression of TF and PAI-1. These data provide further evidence that insulin has an anti-inflammatory effect including the inhibition of TF and PAI-1 expression. These effects suggest a potential beneficial effect of insulin in thrombin formation and fibrinolysis in atherothrombosis.