Contribution of GPR30 for 1,25 dihydroxyvitamin D3 protection in EAE |
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| Authors: | Sandhya Subramanian Lisa M. Miller Marjorie R. Grafe Arthur A. Vandenbark Halina Offner |
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| Affiliation: | (1) Neuroimmunology Research, R&D-31, Portland Veterans Affairs Medical Center, 3710 SW US Veterans Hospital Rd, Portland, OR 97239, USA;(2) Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA;(3) Department of Pathology, Oregon Health & Science University, Portland, OR 97239, USA;(4) Sr. Research Career Scientist, Research Service, Department of Veterans Affairs Medical Center, Portland, OR 97239, USA;(5) Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR 97239, USA;(6) Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, Portland, OR 97239, USA; |
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| 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. |
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