雌激素代谢产物17beta-dihydroequilenin通过NF-κB途径抵消白细胞介素-1α诱导的人内皮细胞炎症介质的表达。,Thrombosis and Haemostasis

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雌激素代谢产物17beta-dihydroequilenin通过NF-κB途径抵消白细胞介素-1α诱导的人内皮细胞炎症介质的表达。
Thrombosis and Haemostasis ( IF 5.0 ) Pub Date : 2006-03-18
Svitlana Demyanets ₁ , Stefan Pfaffenberger , Christoph Kaun , Gersina Rega , Walter S Speidl , Stefan P Kastl , Thomas W Weiss , Philipp J Hohensinner , Wolf Dietrich , Walter Tschugguel , Valery N Bochkov , Ezzat M Awad , Gerald Maurer , Kurt Huber , Johann Wojta

Affiliation

在大多数显示雌激素的心脏和血管保护作用的研究中，都使用17β-雌二醇，但几乎没有关于不同雌激素代谢物可能作用的信息。我们调查了特定的雌激素代谢物是否在对抗人类内皮的炎症激活方面有效。将人内皮细胞与17α-二氢海葵宁，17β-二氢海葵宁，δ-8,9-脱氢雌酮，雌酮和17β-雌二醇孵育，并用白介素（IL）-1α刺激。测定IL-6，IL-8和单核细胞趋化蛋白-1（MCP-1）的表达。浓度为1 microM的17beta-dihydroequilenin和17beta-雌二醇减少了IL-1alpha诱导的IL-6，IL-8和MCP-1的上调，接近对照水平。当两种化合物组合使用时，观察到加和作用。17alpha-dihydroequilenin和delta-8,9-dehydroestrone仅在10 microM时显示相似的抗炎作用，而雌酮则无作用。雌激素受体拮抗剂ICI 182,780逆转了17beta-dihydroequilenin对IL-1alpha诱导的IL-6，IL-8和MCP-1产生的影响。17beta-dihydroequilenin还抑制IL-1alpha诱导的p50和p65易位至细胞核。我们已经确定雌激素代谢产物17β-dihydroequilenin，作为人类内皮细胞炎症激活的抑制剂。如我们的研究所示，特定雌激素的表征可以为量身定制的疗法提供基础，这种疗法可能能够实现血管保护作用而无不良副作用。9-脱氢雌酮仅在10 microM时显示相似的抗炎作用，而雌酮则无作用。雌激素受体拮抗剂ICI 182,780逆转了17beta-dihydroequilenin对IL-1alpha诱导的IL-6，IL-8和MCP-1产生的影响。17beta-dihydroequilenin还抑制IL-1alpha诱导的p50和p65易位至细胞核。我们已经确定雌激素代谢产物17β-dihydroequilenin，作为人类内皮细胞炎症激活的抑制剂。如我们的研究所示，特定雌激素的表征可以为量身定制的疗法提供基础，这种疗法可能能够实现血管保护作用而无不良副作用。9-脱氢雌酮仅在10 microM时显示相似的抗炎作用，而雌酮则无作用。雌激素受体拮抗剂ICI 182,780逆转了17beta-dihydroequilenin对IL-1alpha诱导的IL-6，IL-8和MCP-1产生的影响。17beta-dihydroequilenin还抑制IL-1alpha诱导的p50和p65易位至细胞核。我们已经确定雌激素代谢产物17β-dihydroequilenin，作为人类内皮细胞炎症激活的抑制剂。如我们的研究所示，特定雌激素的表征可以为量身定制的疗法提供基础，这种疗法可能能够实现血管保护作用而无不良副作用。IL-8和MCP-1被雌激素受体拮抗剂ICI 182,780逆转。17beta-dihydroequilenin还抑制IL-1alpha诱导的p50和p65易位至细胞核。我们已经确定雌激素代谢产物17β-dihydroequilenin，作为人类内皮细胞炎症激活的抑制剂。如我们的研究所示，特定雌激素的表征可以为量身定制的疗法提供基础，这种疗法可能能够实现血管保护作用而无不良副作用。IL-8和MCP-1被雌激素受体拮抗剂ICI 182,780逆转。17beta-dihydroequilenin还抑制IL-1alpha诱导的p50和p65易位至细胞核。我们已经确定雌激素代谢产物17β-dihydroequilenin，作为人类内皮细胞炎症激活的抑制剂。如我们的研究所示，特定雌激素的表征可以为量身定制的疗法提供基础，这种疗法可能能够实现血管保护作用而无不良副作用。

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The estrogen metabolite 17beta-dihydroequilenin counteracts interleukin-1alpha induced expression of inflammatory mediators in human endothelial cells in vitro via NF-kappaB pathway.

In most studies showing cardio- and vasculoprotective effects of estrogens, 17beta-estradiol was used and little information on possible effects of different estrogen metabolites is yet available. We investigated whether particular estrogen metabolites are effective in counteracting inflammatory activation of human endothelium. Human endothelial cells were incubated with 17alpha-dihydroequilenin, 17beta-dihydroequilenin, delta-8,9-dehydroestrone, estrone and 17beta-estradiol and stimulated with interleukin (IL)-1alpha. The expression of IL-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1) was determined. 17beta-dihydroequilenin and 17beta-estradiol at a concentration of 1 microM reduced IL-1alpha-induced up regulation of IL-6, IL-8 and MCP-1 close to control levels. When both compounds were used in combination an additive effect was observed. 17alpha-dihydroequilenin and delta-8,9-dehydroestrone showed a similar anti-inflammatory effect only when used at 10 microM whereas estrone had no effect. The effect of 17beta-dihydroequilenin on IL-1alpha-induced production of IL-6, IL-8 and MCP-1 was reversed by the estrogen receptor antagonist ICI 182,780. 17beta-dihydroequilenin also inhibited IL-1alpha-induced translocation of p50 and p65 to the nucleus of the cells. We have identified the estrogen metabolite 17beta-dihydroequilenin, as an inhibitor of inflammatory activation of human endothelial cells. Characterization of specific estrogens--as shown in our study--could provide the basis for tailored therapies, which might be able to achieve vasoprotection without adverse side effects.

更新日期：2019-11-01

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