オオツキ ミチオ   Ootsuki Michio
  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 RU486 antagonizes the inhibitory effect of peroxisome proliferator-activated receptor alpha on interleukin-6 production in vascular endothelial cells
掲載誌名 正式名:The Journal of steroid biochemistry and molecular biology
略  称:J Steroid Biochem Mol Biol
ISSNコード:09600760 (Print)09600760 (Linking)
掲載区分国外
巻・号・頁 81(2),pp.141-146
著者・共著者 Xu, X. Otsuki, M. Sumitani, S. Saito, H. Kouhara, H. Kasayama, S.
担当区分 2nd著者
発行年月 2002
概要 Peroxisome proliferator-acitivated receptor alpha (PPARalpha) is a member of nuclear receptor superfamily. Recent studies have shown that the activators for PPARalpha inhibit the expression of some inflammatory molecules in vascular endothelial cells (ECs) and vascular smooth muscle cells, indicating the anti-inflammatory roles of PPARalpha on vascular walls. In this investigation, we showed that RU486, already proved to be an active anti-glucocorticoid and anti-progesterone agent, blocked the inhibition of tumor necrosis factor (TNF)-alpha-stimulated interleukin-6 (IL-6) production by the PPARalpha activator fenofibrate in human umbilical vein ECs. Transient transfection of bovine aortic ECs with an IL-6 promoter construct demonstrated that RU486 blocked the inhibitory effect of fenofibrate on TNF-alpha-induced IL-6 promoter activity. By fluorescence microscopy, RU486 was found to prevent fenofibrate-induced nuclear translocation of PPARalpha. Thus, RU486 has an antagonizing effect on PPARalpha-mediated down-regulation of IL-6 in vascular ECs. This effect may be exerted by its interference with the nuclear translocation of PPARalpha.
DOI 10.1016/s0960-0760(02)00055-9.
文献番号 12137803