Tissue-Dependent Expression of Estrogen Receptor β in 17β-Estradiol-Mediated Attenuation of Autoimmune CNS Inflammation.
Tissue-Dependent Expression of Estrogen Receptor β in 17β-Estradiol-Mediated Attenuation of Autoimmune CNS Inflammation.
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DOI：
10.2174/1876894601002010197
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发表时间：
2010-01-01
期刊：
影响因子：
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通讯作者：
Offner H
中科院分区：
文献类型：
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作者：
Jones RE;Kaler L;Murphy S;Offner H
使用治疗性雌激素的治疗策略正在开发中，并正在测试多发性硬化症(MS)。MS是一种自身免疫性炎症性疾病，攻击中枢神经系统，损害髓鞘，并产生神经退行性变化，与周期性和慢性进展的功能性神经功能障碍有关。17-雌二醇(17β-estadiol，E_2)处理的嵌合骨髓移植小鼠的实验研究表明，雌激素受体-1(ESR-1，或-α)仅在非造血组织中表达，足以在T淋巴细胞或其他骨髓来源细胞上缺乏ESR-1表达的小鼠中介导有益的神经保护性治疗反应。关于雌激素受体-2(ESR-2，或-β)在E2介导的治疗中的表达要求，我们知之甚少。在这里，我们测试和比较了骨髓移植小鼠不同组织间对ESR-2表达的需求。我们的研究支持ESR-1在E2治疗中的关键作用，并证明非骨髓来源细胞表达的ESR-2在维持ESR-1介导的神经保护反应中发挥作用。
Treatment strategies using therapeutic estrogen are being developed and tested for multiple sclerosis (MS). MS is an autoimmune inflammatory disease that attacks the central nervous system, damages myelin and produces neurode-generative changes associated with periodic and chronic progression of functional neurological deficit. Experimental studies in chimeric bone marrow transplant mice treated with 17β-estradiol (E2) have revealed that the estrogen receptor-1 (Esr-1, or -alpha) expressed exclusively within the non-hematopoietic tissue compartment is sufficient for mediating a beneficial neuroprotective therapeutic response in mice lacking Esr-1 expression on T lymphocytes or other bone marrow-derived cells. Less is known regarding requirements for estrogen receptor-2 (Esr-2, or -beta) expression in E2-mediated therapy. Here, we tested and compared requirements for Esr-2 expression within distinct tissue compartments in bone marrow transplant mice. Our studies support a crucial role for Esr-1 in E2 treatment and demonstrate that Esr-2 expressed by non-bone marrow-derived cells plays a role in sustaining the neuroprotective response mediated through Esr-1.