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The Journal of Immunology, 2003, 171: 6936-6940.
Copyright © 2003 by The American Association of Immunologists

Estrogen Receptor {alpha} Mediates Estrogen’s Immune Protection in Autoimmune Disease

Hong-biao Liu*, Kyi Kyi Loo*, Karen Palaszynski*, Judith Ashouri*, Dennis B. Lubahn{dagger} and Rhonda R. Voskuhl1,*

* Department of Neurology, Reed Neurological Research Center, University of California, Los Angeles, CA 90095; and {dagger} Department of Biochemistry, Child Health and Animal Sciences, University of Missouri, Columbia, MO 65211

Estrogens are known to influence a variety of autoimmune diseases, but it is not known whether their actions are mediated through classic estrogen receptor {alpha} (ER{alpha}). The presence of a functional ER was demonstrated in secondary lymphoid tissues, then ER{alpha} expression was shown at both the RNA and protein levels in these tissues. Use of ER{alpha} knockout mice revealed that both the estrogen-induced disease protection and the estrogen-induced reduction in proinflammatory cytokines were dependent upon ER{alpha} in the prototypic Th1-mediated autoimmune disease experimental autoimmune encephalomyelitis. These findings are central to the design of selective ER modifiers which aim to target biologic responses in specific organ systems.




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