Testosterone alleviates tumor necrosis factor-alpha-mediated tissue factor pathway inhibitor downregulation via suppression of nuclear factor-kappa B in endothelial cells
Testosterone alleviates tumor necrosis factor-alpha-mediated tissue factor pathway inhibitor downregulation via suppression of nuclear factor-kappa B in endothelial cells
复制标题
睾酮通过抑制内皮细胞中的核因子-κ B 减轻肿瘤坏死因子-α 介导的组织因子途径抑制剂下调
DOI：
10.1038/aja.2008.12
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发表时间：
2009-03-01
影响因子：
2.9
通讯作者：
Tan, Xue-Rui
中科院分区：
文献类型：
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作者：
Jin, Hong;Qiu, Wen-Bing;Tan, Xue-Rui
我们先前已经观察到生理浓度的睾酮可以通过内皮细胞中的雄激素受体刺激组织因子途径抑制物（TFPI）基因的表达。本研究进一步研究了睾酮对TFPI水平的影响，以响应炎症细胞因子肿瘤坏死因子-α（TNF-α）。在存在或不存在睾酮或TNF-α的情况下孵育培养的人脐静脉内皮细胞。TFPI蛋白和mRNA水平进行了评估，通过酶联免疫吸附试验和定量实时逆转录聚合酶链反应。为了研究睾酮作用的细胞机制，采用电泳迁移率变动分析法证实核因子-κ B（NF-κ B）易位。结果发现，TNF-α激活NF-κ B后，TFPI蛋白水平较对照组显著下降37.3%（P < 0.001），TFPI mRNA水平也显著下降（P < 0.001）。与TNF-α治疗组相比，30 nmol L-1睾酮浓度增加TFPI的分泌。睾酮显著抑制NF-κ B B DNA结合活性（P < 0.05）。这表明生理睾酮浓度可能通过下调NF-κ B活性对炎症期间TFPI表达发挥其抗血栓形成作用。
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-alpha). Cultured human umbilical vein endothelial cells were incubated in the presence or absence of testosterone or TNF-alpha. 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-kappa B) translocation was confirmed by electrophoretic mobility shift assays. We found that after NF-kappa B was activated by TNF-alpha, 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-alpha-treated group. NF-kappa B 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-kappa B activity.