Estrogen and brain inflammation: Effects on microglial expression of MHC, costimulatory molecules and cytokines

Estrogen and brain inflammation: Effects on microglial expression of MHC, costimulatory molecules and cytokines
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DOI:
10.1016/j.jneuroim.2004.12.016
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发表时间:
2005-04-01
影响因子:
3.3
通讯作者:
Bruce-Keller, AJ
Bruce-Keller, AJ
中科院分区:
医学4区
文献类型:
--
作者:
Dimayuga, FO;Reed, JL;Bruce-Keller, AJ

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为了模拟雌激素对大脑中获得性免疫的影响,我们研究了17 β-雌二醇对与抗原呈递和T细胞活化相关的小胶质细胞参数的影响。具体地,在N9小胶质细胞中检查17 β-雌二醇对I类和II类MHC以及CD 40、CD 80、CD 86、CD 152、CD 28、CD 8、CD 11b、Fas、FasL以及ER α和ER β的基础和LPS诱导的表面染色的影响。此外,测定了17 β-雌二醇对细胞因子(TNF-α、IFN-γ、IL-2、IL-4和IL-10)的基础和LPS诱导的释放的影响。数据表明,雌激素增加IL-10,同时减少从静息和LPS刺激的N9细胞释放TNF α和IFN γ。此外,LPS诱导的MHC 1类,CD 40和CD 86的表面染色显着减弱雌激素预处理。雌激素暴露显著降低了MHC I类和II类、CD 40和CD 152、Fas和FasL阳性细胞的基础百分比。然而,CD 8,CD 86,CD 11b和CD 28不受雌激素的影响,CD 80细胞表面染色显着增加后,雌激素暴露。两者合计,这些数据表明,雌激素可以显着降低小胶质细胞中的适应性免疫的组件,并突出了多方面的调节作用,雌激素对小胶质细胞参数相关的抗原呈递和T细胞相互作用。(C)2005 Elsevier B.V保留所有权利。
To model the effects of estrogen on adaptive immunity in the brain, we examined the effects of 17 beta-estradiol on microglial parameters related to antigen presentation and T cell activation. Specifically, the effects of 17 beta-estradiol on basal and LPS-induced surface staining of Class I and II MHC, as well as CD40, CD80, CD86, CD 152, CD28, CD8, CD11b, Fas, FasL, and also ER alpha and ER beta, were examined in N9 microglial cells. Additionally, the effects of 17 beta-estradiol on basal and LPS-induced release of cytokines (TNF-alpha, IFN-gamma, IL-2, IL-4, and IL-10) were determined. Data indicate that estrogen increases IL-10 while decreasing TNF alpha and IFN gamma release from resting and LPS-stimulated N9 cells. Additionally, LPS-induced surface staining of MHC Class 1, CD40, and CD86 was significantly attenuated by estrogen pretreatment. The basal percentage of cells positive for MHC Class I and II, CD40, and CD152, Fas, and FasL was significantly decreased by estrogen exposure. However, CD8, CD86, CD11b, and CD28 were unaffected by estrogen, and CD80 cell surface staining significantly increased following estrogen exposure. Taken together, these data indicate that estrogen can significantly decrease components of adaptive immunity in microglial cells, and highlight the multi-faceted regulatory effects of estrogen on microglial parameters related to antigen presentation and T cell interaction. (C) 2005 Elsevier B.V All rights reserved.