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

Chang Hee Jung,Yu Mi Kang,Hae Kyeong Yoon,Min Jung Lee,Yoo La Lee,Joong-Yeol Park,Sang-Wook Kang,Woo Je Lee

doi:10.1186/1475-2840-13-41

Abstract

BackgroundVaspin 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.MethodsWe 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.ResultsTreatment 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.ConclusionsVaspin might attenuate the cytokine-induced expression of adhesion molecule genes by inhibiting NF-κB following AMPK activation.

Highlights

Vascular inflammation is a primary event in the pathogenesis of many human diseases, including atherosclerosis, hypertension, and restenosis [1,2,3]
We examined the effects of vaspin on nuclear factor-κB (NF-κB) activation, as well as on the expression of the NF-κB-mediated genes intracellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), E-selectin, and monocyte chemoattractant protein-1 (MCP-1) in vascular endothelial cells
Dose-response studies demonstrated that levels of phosphorylated AMP-activated kinase (AMPK) and Acetyl-CoA carboxylase (ACC) were significantly higher in cells treated with a concentration of vaspin of 50 ng/mL or higher than in control cells (Figure 1C and D)

Summary

Introduction

Vascular inflammation is a primary event in the pathogenesis of many human diseases, including atherosclerosis, hypertension, and restenosis [1,2,3]. The vascular inflammatory reaction is mediated by complex interactions between circulating leukocytes and the endothelium. Activation of endothelial cells by proinflammatory molecules, including tumor necrosis factor α (TNFα), increases the expression of adhesion molecules and the adhesion of leukocytes to the vascular endothelium, which. Various leukocyte adhesion molecules, such as intracellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and E-selectin, as well as various chemokines such as monocyte chemoattractant protein-1 (MCP-1) and IL-8 have been reported to promote atherosclerosis through the NF-κB-dependent coordinated induction [9,10,11,12]. 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

Methods

Results

Conclusion