Omentin plays an anti-inflammatory role through inhibition of TNF-α-induced superoxide production in vascular smooth muscle cells
Omentin plays an anti-inflammatory role through inhibition of TNF-α-induced superoxide production in vascular smooth muscle cells
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DOI：
10.1016/j.ejphar.2012.04.033
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发表时间：
2012-07-05
影响因子：
5
通讯作者：
Yamawaki, Hideyuki
中科院分区：
文献类型：
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作者：
Kazama, Kyosuke;Usui, Tatsuya;Yamawaki, Hideyuki
网膜素是最近发现的一种脂肪细胞因子，其在脉管系统中的作用很大程度上未知。在这里，我们研究了网膜素对平滑肌细胞（SMC）炎症状态的影响。进行蛋白质印迹分析培养的 SMC 中的炎症信号转导。大网膜蛋白（50-300 ng/ml，20 分钟或 24 小时）不会诱导核因子 kappa B (NF-kappa B)、p38 和 JNK 的磷酸化以及血管细胞粘附分子 (VCAM)-1 和环氧合酶-2 的表达。另一方面，肿瘤坏死因子-α（TNF-α；10 ng/ml，20 分钟）诱导的 p38 和 JNK 磷酸化被网膜素预处理以浓度依赖性方式（50-300 ng/ml，30 分钟）显着抑制。 TNF-α（24小时）诱导的VCAM-1表达也被网膜素预处理以浓度依赖性方式显着抑制。 p38 (SB203580) 和 JNK (SP600125) 抑制剂均显着抑制 TNF-α 诱导的 VCAM-1 表达。通过光泽精测定确定，Omentin（300 ng/ml，30 分钟）抑制 TNF-α（1 小时）诱导的烟酰胺腺嘌呤二核苷酸磷酸氧化酶活性。 N-乙酰基-L-半胱氨酸是一种抗氧化剂药物，可显着抑制 TNF-α 诱导的 p38 和 JNK 磷酸化。此外，网膜素（300 ng/ml，30 分钟）显着抑制 TNF-α（24 小时）诱导的单核细胞与 SMC 的粘附。在大鼠离体胸主动脉中，网膜素（300 ng/ml，30 分钟）抑制 TNF-α（24 小时）诱导的 VCAM-1 表达。目前的结果首次证明网膜素通过阻止 SMC 中 TNF-α 诱导的 VCAM-1 表达来发挥抗炎作用。表明网膜素至少部分通过抑制超氧化物产生来阻止 p38 和 JNK 的激活，从而抑制 TNF-α 诱导的 VCAM-1 表达。 (C) 2012 Elsevier B.V. 保留所有权利。
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.