title: Contribution of GPR30 for 1,25 dihydroxyvitamin D₃ protection in EAE.
abstract: Previous studies have demonstrated that vitamin D3-mediated protection in EAE occurs only in females and is dependent on the presence of diestrus levels of 17β-estradiol (E2). To evaluate the role of estrogen receptors in vitamin D3 treatment of EAE, we compared disease severity, CNS histopathology and immunological responses in vehicle and calcitrol (1,25 dihydroxyvitamin D₃) treated WT C57BL/6 mice vs. GPR30 membrane estrogen receptor (MER) knockout mice with MOG-35-55 peptide-induced EAE. Our results demonstrated that vitamin D₃-mediated prevention of clinical signs, CNS cellular lesions and demyelination observed in WT mice was abrogated in GPR30-KO mice with EAE. Regulatory effects of vitamin D₃ treatment that were MER dependent included increased levels of IL-10 and IL-6 secreted by MOG peptide-reactive splenocytes and increased expression of CCL5, CCR1 & CCR3 in spleen tissue. These results demonstrate for the first time that the MER is a key contributor to the E2-dependent effects of vitamin D₃-mediated protection in EAE.
authors: Neuroimmunology Research, R&D-31, Portland Veterans Affairs Medical Center, 3710 SW US Veterans Hospital Rd, Portland, OR 97239, USA.
authors: Sandhya
authors: S
authors: Subramanian
authors: Lisa M
authors: LM
authors: Miller
authors: Marjorie R
authors: MR
authors: Grafe
authors: Arthur A
authors: AA
authors: Vandenbark
authors: Halina
authors: H
authors: Offner
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000627:therapeutic use*; D018946:Chemokine CCL5 / Q000378:metabolism; D019610:Cytoprotection; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006023:Glycoproteins / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000009:adverse effects / Q000276:immunology; D054389:Receptors, CCR1 / Q000378:metabolism; D054397:Receptors, CCR3 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism; D011960:Receptors, Estrogen / Q000276:immunology / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000276:immunology / Q000378:metabolism*
chemical_list: C515301:Ccr1 protein, mouse; C515351:Ccr3 protein, mouse; D018946:Chemokine CCL5; C532507:GPER1 protein, mouse; D006023:Glycoproteins; D015850:Interleukin-6; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D054389:Receptors, CCR1; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; C526792:myelin oligodendrocyte glycoprotein (35-50), Ala(37)-; D016753:Interleukin-10; D002117:Calcitriol