Volume 11, Issue 2 (March 2009) 11, 266–271; 10.1038/aja.2008.12
Testosterone alleviates tumor necrosis factor-alpha-mediated tissue factor pathway inhibitor downregulation via suppression of nuclear factor-kappa B in endothelial cells
Hong Jin1, Wen-Bing Qiu1, Yi-Fang Mei2, Dong-Ming Wang1, Yu-Guang Li1 and Xue-Rui Tan1
1 The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, China 2 The First Affiliated Hospital of Harbin Medical University, Harbin 150081, China
Correspondence: Dr Xue-Rui Tan, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, China. Fax: +86-754-8825-9850 E-mail: Tanxuerui@vip.sina.com
Received 23 June 2008; Revised 3 August 2008; Accepted 21 August 2008; Published online 26 January 2009
Abstract |
We have observed earlier that testosterone at physiological concentrations can stimulate tissue factor pathway inhibitor (TFPI) gene expression through the androgen receptor in endothelial cells. This study further investigated the impact of testosterone on TFPI levels in response to inflammatory cytokine tumor necrosis factor-alpha (TNF-α). Cultured human umbilical vein endothelial cells were incubated in the presence or absence of testosterone or TNF-α. TFPI protein and mRNA levels were assessed by enzyme-linked immunosorbent assay and quantitative real-time reverse transcription polymerase chain reaction. To study the cellular mechanism of testosterone's action, nuclear factor-kappa B (NF-κB) translocation was confirmed by electrophoretic mobility shift assays. We found that after NF-κB was activated by TNF-α, TFPI protein levels declined significantly by 37.3% compared with controls (P < 0.001), and the mRNA levels of TFPI also decreased greatly (P < 0.001). A concentration of 30 nmol L-1 testosterone increased the secretion of TFPI compared with the TNF-α-treated group. NF-κB DNA-binding activity was significantly suppressed by testosterone (P < 0.05). This suggests that physiological testosterone concentrations may exert their antithrombotic effects on TFPI expression during inflammation by downregulating NF-κB activity.
Keywords: nuclear factor-kappa B, testosterone, tissue factor pathway inhibitor
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