Cilostazol represses vascular cell adhesion molecule-1 gene transcription via inhibiting NF-κB binding to its recognition sequence
Cilostazol represses vascular cell adhesion molecule-1 gene transcription via inhibiting NF-κB binding to its recognition sequence
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DOI：
10.1016/s0021-9150(01)00431-2
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发表时间：
2001-09-01
期刊：
影响因子：
5.3
通讯作者：
Kasayama, S
中科院分区：
文献类型：
--
作者：
Otsuki, M;Saito, H;Kasayama, S
西洛他唑是cAMP磷酸二酯酶的特异性抑制剂，用于治疗周围血管疾病的缺血症状。虽然西洛他唑具有抗血小板和血管扩张的特性，但其对血管内皮中粘附分子表达的影响尚不清楚。在本研究中，我们研究了西洛他唑对血管细胞粘附分子-1（VCAM-1）在培养的血管内皮细胞中表达的影响。西洛他唑强烈抑制肿瘤坏死因子（TNF）-α诱导的VCAM-1蛋白及其mRNA的表达。此外，西洛他唑减少TNF-α诱导的U937细胞与血管内皮细胞的粘附。在瞬时转染研究中，西洛他唑抑制TNF-α诱导的VCAM-1启动子的转录激活。电泳迁移率变动分析显示，西洛他唑抑制TNF-α诱导的转录核因子-κ B（NF-κ B）与VCAM-1启动子识别位点结合的增加。然而，西洛他唑未能阻止NF-κ B p65蛋白的核转位。这些数据表明，西洛他唑通过抑制NF-κ B与其识别序列的结合来抑制培养的血管内皮细胞中VCAM-1基因的转录。由于粘附分子的表达是动脉粥样硬化形成过程中最早发生的事件之一，西洛他唑可能至少通过抑制粘附分子的表达而具有预防动脉粥样硬化的潜力。(C)2001爱思唯尔科学爱尔兰有限公司保留所有权利。
Cilostazol is a specific inhibitor of cAMP phosphodiesterase, which is used for treatment of ischemic symptoms of peripheral vascular disease. Although cilostazol has antiplatelet and vasodilator properties, its effect on the expression of adhesion molecules in vascular endothelium is not known. In the present investigation, we examined the effect of cilostazol on the expression of vascular cell adhesion molecule-1 (VCAM-1) in cultured vascular endothelial cells. Cilostazol strongly inhibited tumor necrosis factor (TNF)-alpha -induced expression of VCAM-1 protein and its mRNA. In addition, cilostazol reduced TNF-alpha -induced U937 cell adhesion to the vascular endothelial cells. In transient transfection studies, cilostazol inhibited TNF-alpha -induced transcriptional activation of VCAM-1 promoter. Electrophoretic mobility shift assays revealed that cilostazol repressed TNIF-alpha -induced increase in binding of the transcription nuclear factor-kappaB (NF-kappaB) to its recognition site of VCAM-1 promoter. Cilostazol, however, failed to prevent nuclear translocation of the NF-kappaB p65 protein. These data indicate that cilostazol repressed VCAM-1 gene transcription in cultured vascular endothelial cells, via inhibiting NF-kappaB binding to its recognition sequence. Since the expression of the adhesion molecule is one of the earliest events occurred in atherogenic process, cilostazol might have the potential to prevent atherosclerosis at least via inhibition of the expression of the adhesion molecule. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.