Sex steroid regulation of microglial cell activation - Relevance to multiple sclerosis
Sex steroid regulation of microglial cell activation - Relevance to multiple sclerosis
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DOI：
10.1196/annals.1286.031
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发表时间：
2003-01-01
期刊：
影响因子：
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通讯作者：
Bhatt, R
中科院分区：
文献类型：
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作者：
Drew, PD;Chavis, JA;Bhatt, R
多发性硬化症（MS）在女性中比男性更常见。然而，导致MS性别差异的机制尚不清楚。一些研究表明，性类固醇影响MS的发展和严重程度。例如，妊娠影响MS症状，在妊娠晚期缓解，然后在产后期间加重。此外，含有女性性类固醇的口服避孕药与MS的风险降低和残疾减少有关。实验性自身免疫性脑脊髓炎（EAE）是一种由T细胞对中枢神经系统（CNS）抗原反应引发的自身免疫性疾病。EAE的特点是炎症和脱髓鞘的中枢神经系统，并通过缓解性麻痹的功能一致的MS。最近的研究表明，女性性类固醇可能调制EAE，至少部分地，通过对T细胞的影响。例如，性类固醇在体外将T细胞向Th 2表型转变，并且由Th 2细胞产生的细胞因子通常抑制EAE。活化的小胶质细胞也被认为有助于MS病理学;可能部分是由于产生一氧化氮（NO）和TNF-α分子，其对CNS细胞（包括少突胶质细胞）具有毒性。我们目前正在研究性类固醇在调节与MS相关的小胶质细胞功能中的作用。希望阐明性类固醇调节CNS炎症的机制将为MS的治疗提供未来的治疗方法。
Multiple sclerosis (MS) occurs more commonly in females than males. However, the mechanisms resulting in gender differences in MS are unknown. Several studies have suggested that sex steroids influence the development and severity of MS. For example, pregnancy influences MS symptoms, with remission in the third trimester of gestation, followed by exacerbation in the postpartum period. In addition, oral contraceptives containing female sex steroids have been associated with a lower risk of developing MS and decreased disability. Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disorder initiated by T cells reactive against central nervous system (CNS) antigens. EAE is characterized by inflammation and demyelination of the CNS, and by remittent paralysis-features consistent with MS. Recent studies have suggested that female sex steroids may modulate EAE, at least in part, through effects on T cells. For example, sex steroids shift T cells toward a Th2 phenotype in vitro, and cytokines produced by Th2 cells generally suppress EAE. Activated microglia also are believed to contribute to MS pathology; perhaps due in part to production of nitric oxide (NO) and TNF-alpha molecules which can be toxic to CNS cells, including oligodendrocytes. We are currently investigating the role of sex steroids in modulating microglial cell function in relation to MS. It is hoped that elucidation of the mechanisms by which sex steroids modulate CNS inflammation will lead to future therapies in the treatment of MS.