Michio Otsuki    Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine    Position   Professor and Division head
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	RU486 antagonizes the inhibitory effect of peroxisome proliferator-activated receptor alpha on interleukin-6 production in vascular endothelial cells
Journal	Formal name：The Journal of steroid biochemistry and molecular biology Abbreviation：J Steroid Biochem Mol Biol ISSN code：09600760 (Print)09600760 (Linking)
Domestic / Foregin	Foregin
Volume, Issue, Page	81(2),pp.141-146
Author and coauthor	Xu, X. Otsuki, M. Sumitani, S. Saito, H. Kouhara, H. Kasayama, S.
Authorship	2nd author
Publication date	2002
Summary	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.
Document No.	12137803