Medium-dose estrogen ameliorates experimental autoimmune encephalomyelitis in ovariectomized mice
Medium-dose estrogen ameliorates experimental autoimmune encephalomyelitis in ovariectomized mice
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DOI：
10.1080/1547691x.2016.1223768
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发表时间：
2016-01-01
影响因子：
3.3
通讯作者：
Mahmoudi, Mahmoud
中科院分区：
文献类型：
--
作者：
Haghmorad, Dariush;Salehipour, Zohreh;Mahmoudi, Mahmoud
雌激素是一种神经保护激素，在各种中枢神经系统(CNS)疾病中发挥作用。本研究评估了雌激素在实验性自身免疫性脑脊髓炎(EAE)中的作用，剂量选择为模拟孕期激素的任何抑制潜力。在这里，小鼠去卵巢，2周后用MOG抗原处理诱发EAE。同时，小鼠随后接受(皮下)植入的颗粒，以在21天内提供不同数量的雌激素。连续21天每天监测临床评分和其他参数。治疗结束后，行脑/脊髓组织学检查，检测淋巴细胞浸润情况；采用酶联免疫吸附试验、流式细胞仪、实时荧光定量聚合酶链式反应等方法检测T细胞亚群。用实时定量聚合酶链式反应检测中枢神经系统转录因子的表达水平；用流式细胞仪检测T细胞分化程度。结果表明，雌激素抑制了EAE的发生发展。组织学检查显示中枢神经系统内有少量的白细胞渗入。高、中剂量雌激素可增加T(H)2和T-reg细胞产生IL-4、IL-10和转化生长因子(TGF)-α，但同时显著减少干扰素(IFN)-、IL-17和IL-6的产生。流式细胞仪检测显示T(H)1和T(H)17细胞百分率显著降低，T-reg和T(H)2细胞百分率显著升高。实时荧光定量聚合酶链式反应结果显示，高、中剂量雌激素处理降低了T-bet和ROR-t因子的表达，但增强了Foxp3和GATA3的表达。总而言之，这些结果表明，中等剂量的雌激素--类似于怀孕时的雌激素水平--可以潜在地降低自身免疫性EAE以及可能的其他自身免疫性病理的发生率和严重性。
Estrogen is a neuro-protective hormone in various central nervous system (CNS) disorders. The present study evaluated the role of estrogen during experimental autoimmune encephalomyelitis (EAE) at doses selected to mimic any suppressive potential from the hormone during pregnancy. Here, mice were ovariectomized and then 2 weeks later treated with MOG antigen to induce EAE. Concurrently, mice then received (subcutaneously) an implanted pellet to deliver varying estrogen amounts over a 21-day period. Clinical scores and other parameters were monitored daily for the 21 days. At the end of the period, brain/spinal cord histology was performed to measure lymphocyte infiltration; T-cell profiles were determined through ELISA, flow cytometry, and real-time PCR. Transcription factor expression levels in the CNS were assessed using real-time PCR; T-cell differentiation was evaluated via flow cytometry. The results demonstrated that estrogen inhibited development of EAE. Histological studies revealed limited leukocyte infiltration into the CNS. High and medium dose of estrogen increased T(H)2 and T-reg cell production of interleukin (IL)-4, IL-10, and transforming growth factor (TGF)-, but concurrently resulted in a significant reduction in production of interferon (IFN)-, IL-17, and IL-6. Flow cytometry revealed there were also significant decreases in the percentages of T(H)1 and T(H)17 cells, as well as significant increase in percentages of T-reg and T(H)2 cells in the spleen and lymph nodes. Real-time PCR results indicated that high- and medium-dose estrogen treatments reduced T-bet and ROR-t factor expression, but enhanced Foxp3 and GATA3 expression. Collectively, these results demonstrated that a medium dose of estrogen - similar to a pregnancy level of estrogen - could potentially reduce the incidence and severity of autoimmune EAE and possibly other autoimmune pathologies.