Dimayuga Filomena O, Reed Janelle L, Carnero Genevieve A, Wang Chunmei, Dimayuga Edgardo R, Dimayuga Vanessa M, Perger Andrea, Wilson Melinda E, Keller Jeffrey N, Bruce-Keller Annadora J
Department of Anatomy and Neurobiology, University of Kentucky, MN 222 Chandler Medical Center, Lexington, KY 40536-0298, USA.
J Neuroimmunol. 2005 Apr;161(1-2):123-36. doi: 10.1016/j.jneuroim.2004.12.016.
To model the effects of estrogen on adaptive immunity in the brain, we examined the effects of 17beta-estradiol on microglial parameters related to antigen presentation and T cell activation. Specifically, the effects of 17beta-estradiol on basal and LPS-induced surface staining of Class I and II MHC, as well as CD40, CD80, CD86, CD152, CD28, CD8, CD11b, Fas, FasL, and also ERalpha and ERbeta, were examined in N9 microglial cells. Additionally, the effects of 17beta-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 TNFalpha and IFNgamma release from resting and LPS-stimulated N9 cells. Additionally, LPS-induced surface staining of MHC Class I, 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.
为模拟雌激素对大脑中适应性免疫的影响，我们研究了17β-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。具体而言，在N9小胶质细胞中检测了17β-雌二醇对I类和II类主要组织相容性复合体（MHC）以及CD40、CD80、CD86、CD152、CD28、CD8、CD11b、Fas、FasL，以及雌激素受体α（ERα）和雌激素受体β（ERβ）的基础水平和脂多糖（LPS）诱导的表面染色的影响。此外，还测定了17β-雌二醇对基础水平和LPS诱导的细胞因子（肿瘤坏死因子-α、干扰素-γ、白细胞介素-2、白细胞介素-4和白细胞介素-10）释放的影响。数据表明，雌激素可增加白细胞介素-10的水平，同时减少静息和LPS刺激的N9细胞中肿瘤坏死因子-α和干扰素-γ的释放。此外，雌激素预处理可显著减弱LPS诱导的I类MHC、CD40和CD86的表面染色。雌激素暴露可显著降低I类和II类MHC、CD40、CD152、Fas和FasL阳性细胞的基础百分比。然而，CD8、CD86、CD11b和CD28不受雌激素影响，雌激素暴露后CD80细胞表面染色显著增加。综上所述，这些数据表明雌激素可显著降低小胶质细胞中适应性免疫的成分，并突出了雌激素对与抗原呈递和T细胞相互作用相关的小胶质细胞参数的多方面调节作用。
