Estrogen receptor alpha mediates estrogen's immune protection in autoimmune disease.
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 (ERalpha). The presence of a functional ER was demonstrated in secondary lymphoid tissues, then ERalpha expression was shown at both the RNA and protein levels in these tissues. Use of ERalpha knockout mice revealed that both the estrogen-induced disease protection and the estrogen-induced reduction in proinflammatory cytokines were dependent upon ERalpha 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.
Liu
Hong-biao
HB
Department of Neurology, Reed Neurological Research Center, University of California, Los Angeles, CA 90095, USA.
Loo
Kyi Kyi
KK
Palaszynski
Karen
K
Ashouri
Judith
J
Lubahn
Dennis B
DB
Voskuhl
Rhonda R
RR
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control*; D004964:Estriol / Q000008:administration & dosage; D047628:Estrogen Receptor alpha; D004967:Estrogens / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D016207:Cytokines; D047628:Estrogen Receptor alpha; D004967:Estrogens; D018836:Inflammation Mediators; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D004964:Estriol