Sex hormone modulation of proinflammatory cytokine and C-reactive protein expression in macrophages from older men and postmenopausal women.
Sex hormone modulation of proinflammatory cytokine and C-reactive protein expression in macrophages from older men and postmenopausal women.
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DOI：
10.1677/joe-10-0057
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发表时间：
2010-08
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影响因子：
--
通讯作者：
Lamon-Fava S
中科院分区：
文献类型：
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作者：
Corcoran MP;Meydani M;Lichtenstein AH;Schaefer EJ;Dillard A;Lamon-Fava S
炎症在冠心病（CHD）的发生和发展中起着核心作用。性激素雌激素和睾酮已被证明可以通过影响来自年轻个体的人巨噬细胞中细胞因子的表达来调节炎症反应。尚未研究这些激素对从CHD年龄相关人群获得的巨噬细胞中促炎标志物表达的影响。人单核细胞衍生的巨噬细胞（HMDM）获自健康的血脂正常的男性和绝经后女性（年龄50-70岁），并在自体血清中与生理和超生理浓度的雌激素或睾酮一起沿着培养。用氧化低密度脂蛋白（oxLDL）刺激HMDM，并测定细胞因子TNF-α、IL-6和IL-1β以及急性时相蛋白CRP的表达。生理和超生理浓度的睾酮均能降低TNF-α的表达和分泌，降低IL-1β的表达，但对IL-6和CRP的表达无影响。雌激素不改变TNF-α、IL-6和IL-1β的表达。雌激素引起CRP表达的可变反应，与供体血浆小而密LDL胆固醇浓度呈正相关。观察到的任何效应均无性别差异。我们的研究结果表明，睾酮可能通过降低巨噬细胞TNF-α表达发挥抗炎作用，而雌激素对巨噬细胞CRP表达的影响可能取决于细胞外脂质环境。
Inflammation plays a central role in the development and progression of coronary heart disease (CHD). The sex hormones estrogen and testosterone have been shown to modify the inflammatory response by influencing cytokine expression in human macrophage cells obtained from younger individuals. The effect of these hormones on the expression of proinflammatory markers in macrophages obtained from a CHD-age relevant population has not been studied. Human monocyte-derived macrophage cells (HMDM) were obtained from healthy normolipidemic men and postmenopausal women (age 50-70 years), and cultured in autologous serum along with both physiological and supraphysiological concentrations of estrogen or testosterone. HMDM were stimulated with oxidized low density lipoproteins (oxLDL) and the expression of the cytokines TNF-α, IL-6, and IL-1β, and of the acute-phase protein CRP was measured. Both physiological and supraphysiological concentrations of testosterone reduced the expression and secretion of TNF-α and reduced the expression of IL-1β, but did not affect IL-6 or CRP expression. Estrogen did not modify the expression of TNF-α, IL-6, and IL-1β. Estrogen caused a variable response in CRP expression that was positively associated with the donor’s plasma small dense LDL cholesterol concentration. There were no gender differences in any of the observed effects. Our results indicate that testosterone may exert anti-inflammatory effects by reducing macrophage TNF-α expression while the effects of estrogen on macrophage CRP expression may depend upon the extracellular lipid environment.