オオツキ　ミチオ   Michio Otsuki   大月　道夫    所属   医学部 医学科（東京女子医科大学病院）    職種   教授・基幹分野長
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Cilostazol represses vascular cell adhesion molecule-1 gene transcription via inhibiting NF-kappaB binding to its recognition sequence
掲載誌名	正式名：Atherosclerosis 略　 称：Atherosclerosis ISSNコード：00219150 (Print)00219150 (Linking)
掲載区分	国外
巻・号・頁	158(1),pp.121-128
著者・共著者	Otsuki, M. Saito, H. Xu, X. Sumitani, S. Kouhara, H. Kurabayashi, M. Kasayama, S.
担当区分	筆頭著者
発行年月	2001
概要	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 TNF-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.
DOI	10.1016/s0021-9150(01)00431-2.
文献番号	11500182