Contribution of GPR30 for 1,25 dihydroxyvitamin D 3 protection in EAE

Sandhya Subramanian; Lisa M. Miller; Marjorie R. Grafe; Arthur A. Vandenbark; Halina Offner

doi:10.1007/s11011-011-9266-6

Contribution of GPR30 for 1,25 dihydroxyvitamin D ₃ protection in EAE

Sandhya Subramanian, Lisa M. Miller, Marjorie R. Grafe, Arthur A. Vandenbark, Halina Offner

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

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 D ₃) 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 D ₃-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 D ₃ 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 D ₃-mediated protection in EAE.

Original language	English (US)
Pages (from-to)	29-35
Number of pages	7
Journal	Metabolic brain disease
Volume	27
Issue number	1
DOIs	https://doi.org/10.1007/s11011-011-9266-6
State	Published - Mar 2012

Keywords

1,25 dihydroxyvitamin D
EAE
Estrogen
GPR30

ASJC Scopus subject areas

Biochemistry
Clinical Neurology
Cellular and Molecular Neuroscience

Access to Document

10.1007/s11011-011-9266-6

Cite this

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title = "Contribution of GPR30 for 1,25 dihydroxyvitamin D 3 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 D 3) 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 D 3-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 D 3 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 D 3-mediated protection in EAE.",

keywords = "1,25 dihydroxyvitamin D, EAE, Estrogen, GPR30",

author = "Sandhya Subramanian and Miller, {Lisa M.} and Grafe, {Marjorie R.} and Vandenbark, {Arthur A.} and Halina Offner",

note = "Funding Information: Acknowledgements The authors wish to thank Ms. Eva Niehaus for assistance in preparing the manuscript. This work was supported by National Multiple Sclerosis Society grant RG3107-D-6. This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. The contents do not represent the views of the Department of Veterans Affairs or the United States Government.",

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AU - Offner, Halina

N1 - Funding Information: Acknowledgements The authors wish to thank Ms. Eva Niehaus for assistance in preparing the manuscript. This work was supported by National Multiple Sclerosis Society grant RG3107-D-6. This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. The contents do not represent the views of the Department of Veterans Affairs or the United States Government.

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N2 - 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 D 3) 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 D 3-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 D 3 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 D 3-mediated protection in EAE.

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