Effects of 17 beta-estradiol on cytokine-induced endothelial cell adhesion molecule expression
Effects of 17 beta-estradiol on cytokine-induced endothelial cell adhesion molecule expression
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DOI：
10.1172/jci118774
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发表时间：
1996-07-01
影响因子：
15.9
通讯作者：
Bender, JR
中科院分区：
文献类型：
--
作者：
CaulinGlaser, T;Watson, CA;Bender, JR
动脉粥样硬化的最早期事件之一是循环单核白细胞和内皮细胞的相互作用。内皮细胞（EC）被细胞因子激活导致粘附分子的表达和趋化因子的产生，分别增加白细胞粘附和募集。绝经前女性动脉粥样硬化的发病率显著低于具有相似风险特征的年龄匹配男性，因为雌激素具有基因调节作用，我们研究了17 β-雌二醇（E（2））是否能抑制精氨酸介导的EC粘附分子转录激活。（雌激素受体阳性）在无性腺激素的培养基中繁殖，并在IL-1活化前用E（2）预处理48小时，通过FACS（R）分析检测，E（2）强烈地（60-80%）抑制IL-1介导的膜E-选择素和血管细胞粘附分子-1的诱导，以及细胞间粘附分子-1的过度诱导，17 α-雌二醇（一种无活性的E（2）立体异构体）没有影响。这种抑制与稳态诱导的E-选择素mRNA水平的类似降低相关，并被E（2）拮抗剂ICI 164，384所消除，证明了一种特异性的雌激素受体介导的效应。核径流证实了在转录水平上的抑制。
One of the earliest events in atherosclerosis is interaction of circulating mononuclear leukocytes and the endothelium. Endothelial cell (EC) activation by cytokines results in expression of adhesion molecules and production of chemotactic factors, augmenting leukocyte adhesion and recruitment, respectively, The incidence of atherosclerosis in premenopausal women is significantly less than that observed in age-matched males with similar risk profiles, Because estrogen has gene regulatory effects, we investigated whether 17 beta-estradiol (E(2)) can inhibit cytokine-mediated EC adhesion molecule transcriptional activation, Cultured human umbilical vein EC (estrogen receptor-positive) were propagated in gonadal hormone-free medium and were E(2)-pretreated for 48 h before IL-1 activation, Detected by FACS(R) analysis, E(2) strongly (60-80%) inhibited IL-l-mediated membrane E-selectin and vascular cell adhesion molecule-1 induction, and intercellular adhesion molecule-1 hyperinduction, 17 alpha-estradiol (an inactive E(2) stereoisomer) had no effect. This inhibition correlated with similar reductions in steady state-induced E-selectin mRNA levels, and was abrogated by the E(2) antagonist ICI 164,384, demonstrating a specific, estrogen receptor-mediated effect, Nuclear run-offs confirmed suppression at the transcriptional level, The implications of these results for the cardiovascular protective role of estrogen are discussed.