Vaspin inhibits cytokine-induced nuclear factor-kappa B activation and adhesion molecule expression via AMP-activated protein kinase activation in vascular endothelial cells.

Vaspin inhibits cytokine-induced nuclear factor-kappa B activation and adhesion molecule expression via AMP-activated protein kinase activation in vascular endothelial cells.
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DOI:
10.1186/1475-2840-13-41
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发表时间:
2014-02-12
影响因子:
9.3
通讯作者:
Park JY
Park JY
中科院分区:
医学1区
文献类型:
--
作者:
Jung CH;Lee MJ;Kang YM;Lee YL;Yoon HK;Kang SW;Lee WJ;Park JY

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Vaspin是最近在糖尿病大鼠内脏脂肪组织中发现的一种脂肪细胞因子,具有抗糖尿病和抗动脉粥样硬化作用。我们假设vaspin通过激活血管内皮细胞中amp活化蛋白激酶(AMPK)来阻止炎症细胞因子诱导的核因子κB (NF-κB)活化。我们检测了vaspin对NF-κB活化和NF-κB介导的基因细胞间粘附分子-1 (ICAM-1)、血管细胞粘附分子-1 (VCAM-1)、e-选择素和单核细胞趋化蛋白-1 (MCP-1)表达的影响。使用人主动脉内皮细胞(HAECS)。肿瘤坏死因子α (TNFα)作为促炎细胞因子的代表。vaspin处理显著增加AMPK和乙酰辅酶a羧化酶(AMPK的下游靶点)的磷酸化。此外,vaspin显著降低tnf α诱导的NF-κB活化,以及粘附分子ICAM-1、VCAM-1、e -选择素和MCP-1的表达。这些作用在转染ampk α1特异性小干扰RNA后被消除。在THP-1细胞的粘附实验中,vaspin以ampk依赖的方式降低tnf α诱导的单核细胞对HAECS的粘附。Vaspin可能通过抑制AMPK激活后的NF-κB来减弱细胞因子诱导的粘附分子基因的表达。
Vaspin is an adipocytokine that was recently identified in the visceral adipose tissue of diabetic rats and has anti-diabetic and anti-atherogenic effects. We hypothesized that vaspin prevents inflammatory cytokine-induced nuclear factor-kappa B (NF-κB) activation by activating AMP-activated protein kinase (AMPK) in vascular endothelial cells. We examined the effects of vaspin on NF-κB activation and the expression of the NF-κB-mediated genes intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and monocyte chemoattractant protein-1 (MCP-1). Human aortic endothelial cells (HAECS) were used. Tumor necrosis factor alpha (TNFα) was used as a representative proinflammatory cytokine. Treatment with vaspin significantly increased the phosphorylation of AMPK and acetyl-CoA carboxylase, the down-stream target of AMPK. Furthermore, treatment with vaspin significantly decreased TNFα-induced activation of NF-κB, as well as the expression of the adhesion molecules ICAM-1, VCAM-1, E-selectin, and MCP-1. These effects were abolished following transfection of AMPKα1-specific small interfering RNA. In an adhesion assay using THP-1 cells, vaspin reduced TNFα-induced adhesion of monocytes to HAECS in an AMPK-dependent manner. Vaspin might attenuate the cytokine-induced expression of adhesion molecule genes by inhibiting NF-κB following AMPK activation.
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