GPR30, but not estrogen receptor-alpha, is crucial in the treatment of experimental autoimmune encephalomyelitis by oral ethinyl estradiol.
GPR30, but not estrogen receptor-alpha, is crucial in the treatment of experimental autoimmune encephalomyelitis by oral ethinyl estradiol.
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DOI：
10.1186/1471-2172-11-20
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发表时间：
2010-04-19
期刊：
影响因子：
3
通讯作者：
Offner H
中科院分区：
文献类型：
--
作者：
Yates MA;Li Y;Chlebeck PJ;Offner H
在卵巢激素高分泌期（如怀孕）多发性硬化症的缓解引起了人们对雌激素治疗自身免疫性疾病的潜力的极大兴趣。先前的工作已经确定，17β-雌二醇可以抑制实验性自身免疫性脑脊髓炎（EAE）的发作，而炔雌醇（EE）可以减轻已建立的疾病的严重程度。本研究探讨了雌激素受体α（ERα）和G蛋白偶联雌激素受体（GPR 30或GPER）对EE治疗EAE能力的影响。EE降低了野生型和ERα敲除（ERKO）小鼠的疾病严重程度，但没有改变GPR 30 KO组的疾病。抗炎IL-10的产生在EE-ERKO小鼠（其显示疾病减轻）中增加，但在EE-GPR 30 KO小鼠（其没有改善疾病）中没有增加。在ERKO和GPR 30 KO动物中EE治疗后IL-10的差异产生可能是对疾病严重程度的明显不同影响的原因。与ERKO对照相比，ERKO-EE中IL-10的增加可能是减少已确诊疾病的重要因素。EE不能减少GPR 30 KO小鼠的疾病，表明GPR 30在调节免疫反应性方面具有重要但尚未确定的作用。
Remission of multiple sclerosis during periods of high ovarian hormone secretion (such as pregnancy) has led to a great deal of interest in the potential for estrogens to treat autoimmune disease. Previous work has established that 17β-estradiol can inhibit onset of experimental autoimmune encephalomyelitis (EAE), while ethinyl estradiol (EE) can reduce the severity of established disease. In the current study, the influence of estrogen receptor-α (ERα) and the G-protein coupled estrogen receptor (GPR30 or GPER) on EE's ability to treat EAE was explored. EE reduced disease severity in wild-type and ERα knockout (ERKO) mice, but did not alter disease in the GPR30KO group. Production of anti-inflammatory IL-10 increased in EE-ERKO mice (which showed reduced disease) but not in EE-GPR30KO mice (who did not have improved disease). Differential production of IL-10 following EE treatment in ERKO and GPR30KO animals may be responsible for the distinctly different effects on disease severity. Increased IL-10 in ERKO-EE compared to ERKO-Controls is likely to be an important factor in reducing established disease. The inability of EE to reduce disease in GPR30KO mice indicates an important but still undefined role for GPR30 in regulating immune reactivity.
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影响因子：
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作者：
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