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Testosterone inhibits tumor necrosis factor-alpha-induced vascular cell adhesion molecule-1 expression in human
Haruhiko Hatakeyama1, Makoto Nishizawa, Atsushi Nakagawa
1Department of Internal Medicine, Division of Endocrinology, Kanazawa Medical University, Ishikawa 920-0293, Japan. hataha@kanazawa-med.ac.jp
Abstract:
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.