GPR30, but not estrogen receptor-alpha, is crucial in the treatment of experimental autoimmune encephalomyelitis by oral ethinyl estradiol.
BACKGROUND
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 17beta-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-alpha (ERalpha) and the G-protein coupled estrogen receptor (GPR30 or GPER) on EE's ability to treat EAE was explored.


RESULTS
EE reduced disease severity in wild-type and ERalpha 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).


CONCLUSIONS
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.
Yates
Melissa A
MA
Neuroimmunology Research, Portland VA Medical Center, Portland, OR, USA.
Li
Yuexin
Y
Chlebeck
Peter J
PJ
Offner
Halina
H
D000284:Administration, Oral; D000818:Animals; D002469:Cell Separation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000096:biosynthesis; D004967:Estrogens / Q000008:administration & dosage*; D004997:Ethinyl Estradiol / Q000008:administration & dosage*; D005260:Female; D005434:Flow Cytometry; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis*
D047628:Estrogen Receptor alpha; D004967:Estrogens; C532507:GPER1 protein, mouse; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D016753:Interleukin-10; D004997:Ethinyl Estradiol
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