Testosterone inhibits tumor necrosis factor-alpha-induced vascular cell adhesion molecule-1 expression in human aortic endothelial cells.
We investigated the effect of testosterone (T) on tumor necrosis factor-alpha (TNF-alpha)-induced expression of vascular cell adhesion molecule-1 (VCAM-1) in human aortic endothelial cells. Incubation of these cells with T resulted in a dose-dependent reduction in the expression, with this reduction completely abolished by a selective androgen receptor blocker. Electrophoretic mobility shift assay demonstrated that T inhibited TNF-alpha-induced activation of the transcriptional nuclear factor-kappaB, which is critical for the inducible expression of VCAM-1, probably through the suppression of the nuclear translocation. Our results may suggest an inhibitory effect of T on atherogenesis, providing a novel insight into the consideration of the pathogenesis of atherosclerosis.
Hatakeyama
Haruhiko
H
Department of Internal Medicine, Division of Endocrinology, Kanazawa Medical University, Ishikawa 920-0293, Japan. hataha@kanazawa-med.ac.jp
Nishizawa
Makoto
M
Nakagawa
Atsushi
A
Nakano
Shigeru
S
Kigoshi
Toshikazu
T
Uchida
Kenzo
K
D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001483:Base Sequence; D015152:Blotting, Northern; D002478:Cells, Cultured; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics
D017931:DNA Primers; D016328:NF-kappa B; D012333:RNA, Messenger; D011944:Receptors, Androgen; D019010:Vascular Cell Adhesion Molecule-1; D013739:Testosterone