Antiinflammatory effects of estrogen on microglial activation
Antiinflammatory effects of estrogen on microglial activation
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DOI：
10.1210/en.141.10.3646
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发表时间：
2000-10-01
期刊：
影响因子：
4.8
通讯作者：
Mattson, MP
中科院分区：
文献类型：
--
作者：
Bruce-Keller, AJ;Keeling, JL;Mattson, MP
在本研究中，描述了17 β-雌二醇对小胶质细胞活化的影响。雌激素替代疗法与年龄相关的神经退行性疾病（如阿尔茨海默病）的严重程度降低有关，雌激素在脑外具有强效的免疫抑制特性。为了确定小胶质细胞在雌激素介导的神经保护中可能发挥的作用，在脂多糖、佛波酯或干扰素免疫刺激之前或期间，用增加剂量的17 β-雌二醇处理原代大鼠小胶质细胞和N9小胶质细胞系。-γ。用17 β-雌二醇预处理，而不是17 α-雌二醇或孕酮，剂量依赖性衰减小胶质细胞超氧化物释放和吞噬活性。此外，17 β-雌二醇减弱诱导型一氧化氮合酶蛋白表达的增加，但不改变核因子-κ B活化。抗雌激素ICI 182，780可阻断17 β-雌二醇的抗雌激素作用。此外，17 β-雌二醇诱导p42/p44丝裂原活化蛋白激酶（MAP激酶）的快速磷酸化，MAP激酶抑制剂PD 98059阻断了17 β-雌二醇的抑制作用。总体而言，这些结果表明MAP激酶的雌激素受体依赖性激活参与小胶质细胞中雌激素介导的抗炎途径。这些结果描述了一种新的机制，雌激素可以减轻神经退行性疾病的进展，并提出了新的途径，在临床环境中的治疗干预。
In the present study the effects of 17 beta-estradiol on microglial activation are described. Estrogen replacement therapy has been associated with decreased severity of age-related neurodegenerative diseases such as Alzheimer's disease, and estrogens have potent immunosuppressive properties outside of the brain. To determine the role that microglial cells might play in estrogen-mediated neuroprotection, primary rat microglia and N9 microglial cell lines were treated with increasing doses of 17 beta-estradiol before or during immunostimulation by lipopolysaccharide, phorbol ester, or interferon-gamma. Pretreatment with 17 beta-estradiol, but not 17 alpha-estradiol or progesterone, dose dependently attenuated microglial superoxide release and phagocytic activity. Additionally, 17 beta-estradiol attenuated increases in inducible nitric oxide synthase protein expression, but did not alter nuclear factor-kappa B activation. The antiinflammatory effects of 17 beta-estradiol were blocked by the antiestrogen ICI 182,780. Additionally, 17 beta-estradiol induced rapid phosphorylation of the p42/p44 mitogen-activated protein kinase (MAP kinase), and the MAP kinase inhibitor PD 98059 blocked the antiinflammatory effects of 17 beta-estradiol. Overall, these results suggest that estrogen receptor-dependent activation of MAP kinase is involved in estrogen-mediated antiinflammatory pathways in microglial cells. These results describe a novel mechanism by which estrogen may attenuate the progression of neurodegenerative disease and suggest new pathways for therapeutic intervention in clinical settings.