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Pharmacol Res. 2011 Nov;64(5):493-500. doi: 10.1016/j.phrs.2011.06.001. Epub 2011 Jun 12.

Vaspin prevents TNF-α-induced intracellular adhesion molecule-1 via inhibiting reactive oxygen species-dependent NF-κB and PKCθ activation in cultured rat vascular smooth muscle cells.

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Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034-8628, Japan.


Vaspin (visceral adipose tissue-derived serine protease inhibitor) was recently identified as a novel adipocytokine with insulin-sensitizing effects. We hypothesized that vaspin could play a role in vascular inflammation. To test the hypothesis, we investigated the effects of vaspin on TNF-α-stimulated vascular smooth muscle cells (SMCs) focusing on inflammatory signal transduction. Vascular SMCs from mesenteric artery of male Wistar rats were treated with TNF-α (5-10 ng/ml, 20 min-6 h) in the absence or presence of vaspin (1-300 ng/ml, pretreatment for 24 h). Western blotting was performed to analyze the cellular signal. Reactive oxygen species (ROS) generation was fluorometrically measured using 2',7'-diclorofluorescein diacetate. Vaspin alone treatment had no effect on vascular SMCs morphology and cellular signal. Vaspin significantly decreased the TNF-α-induced monocyte adhesion to SMCs. Vaspin significantly inhibited the protein expression of intracellular adhesion molecule (ICAM)-1 and the phosphorylation of NF-κB and protein kinase C (PKC)θ induced by TNF-α. Both of NF-κB and novel PKC inhibitors significantly attenuated the TNF-α-induced ICAM-1 expression. Moreover, vaspin inhibited TNF-α-induced ROS generation. An anti-oxidant, N-acetyl-L-cysteine blocked the TNF-α-induced activation of NF-κB, PKCθ and expression of ICAM-1. The present results demonstrated for the first time that vaspin inhibits TNF-α-induced expression of ICAM-1 via preventing the ROS generation and subsequent activation of NF-κB and PKCθ. Consequently, vaspin could play inhibitory roles on inflammatory states of vascular SMCs.

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