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
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
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DOI：
10.1210/jc.87.3.1419
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发表时间：
2002-03-01
影响因子：
5.8
通讯作者：
Dandona, P
中科院分区：
文献类型：
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作者：
Aljada, A;Ghanim, H;Dandona, P
我们最近证明，输注低剂量胰岛素可降低 MNC 中核内 NF-κB（一种促炎转录因子）含量，同时还降低 NF-κB 依赖性促炎细胞因子和粘附分子的血浆浓度。我们现在测试了胰岛素对促炎转录因子、早期生长反应 1 (Egr-1) 以及组织因子 (TF) 和纤溶酶原激活剂抑制剂 1 (PAI-1) 血浆浓度的影响，这两种主要蛋白质的表达受 Egr-1 调节。 10 名肥胖受试者在空腹状态下以 2 IU/h 的速度输注含 5% 葡萄糖 (100 mL/h) 和 KCl (8 mmol/h) 的胰岛素 4 小时。在0、2、4和6小时时获取血样。分离 MNC，制备其总匀浆和核级分，并通过电泳迁移率变动测定 (EMSA) 测量 Egr-1。通过ELISA测定血浆TF和PAI-1。 Egr-1 在 2 小时（基础水平的 66 +/- 14%）和 4 小时（基础水平的 47 +/- 17%；P < 0.01）显着下降。胰岛素输注后 2 小时（基础水平的 57 +/- 6.7%）和 4 小时（基础水平的 5 8 +/- 8.3%；P < 0.001），PAI-1 水平（基础 = 100%）显着下降。血浆 IF 水平（基础 = 1001%）在 2 小时时降至基础水平的 76 +/- 7.7%，在 4 小时时降至基础水平的 85 +/- 10.4%（P < 0.05）。因此，胰岛素减少核内Egr-1以及TF和PAI-1的表达。这些数据进一步证明胰岛素具有抗炎作用，包括抑制 TF 和 PAI-1 表达。这些作用表明胰岛素对动脉粥样硬化血栓形成中的凝血酶形成和纤维蛋白溶解具有潜在的有益作用。
We have recently demonstrated that an infusion of a low dose of insulin reduces the intranuclear NF-kappaB (a pro-inflammatory transcription factor) content in MNC while also reducing the plasma concentration of NF-kappaB 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 (5 8 +/- 8.3% of the basal level; P < 0.001). Plasma IF levels (basal = 1001%) 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.