Omentin plays an anti-inflammatory role through inhibition of TNF-α-induced superoxide production in vascular smooth muscle cells

Omentin is a recently identified adipocytokine and its effect in vasculature is largely unknown. Here we examined the effects of omentin on smooth muscle cells (SMCs) inflammatory states. Western blotting was performed to analyze inflammatory signal transduction in cultured SMCs. Phosphorylation of nuclear factor-kappa B (NF-kappa B), p38 and JNK, and expression of vascular cell adhesion molecule (VCAM)-1 and cyclooxygenase-2 were not induced by omentin (50-300 ng/ml, 20 min or 24 h). On the other hand, tumor necrosis factor-alpha (TNF-alpha; 10 ng/ml, 20 min)-induced phosphorylation of p38 and JNK was significantly inhibited by omentin pretreatment in a concentration-dependent manner (50-300 ng/ml, 30 min). TNF-alpha (24 h)-induced expression of VCAM-1 was also significantly inhibited by omentin pretreatment in a concentration-dependent manner. Both inhibitor of p38 (SB203580) and JNK (SP600125) significantly inhibited TNF-alpha-induced VCAM-1 expression. Omentin (300 ng/ml, 30 min) inhibited TNF-alpha (1 h)-induced nicotinamide adenine dinucleotide phosphate oxidase activity as determined by lucigenin assay. An antioxidant drug, N-acetyl-L-cysteine significantly inhibited TNF-alpha-induced phosphorylation of p38 and JNK. Furthermore, omentin (300 ng/ml, 30 min) significantly inhibited TNF-alpha (24 h)-induced monocytic cells adhesion to SMCs. In rat isolated thoracic aorta, omentin (300 ng/ml, 30 min) inhibited TNF-alpha (24 h)-induced VCAM-1 expression. The present results demonstrate for the first time that omentin plays an anti-inflammatory role by preventing the TNF-alpha-induced VCAM-1 expression in SMCs. It is suggested that omentin inhibits TNF-alpha-induced VCAM-1 expression via preventing the activation of p38 and JNK at least in part through inhibition of superoxide production. (C) 2012 Elsevier B.V. All rights reserved.