TY - JOUR
T1 - Contribution of GPR30 for 1,25 dihydroxyvitamin D 3 protection in EAE
AU - Subramanian, Sandhya
AU - Miller, Lisa M.
AU - Grafe, Marjorie
AU - Vandenbark, Arthur A.
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.
PY - 2012/3
Y1 - 2012/3
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.
AB - 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.
KW - 1,25 dihydroxyvitamin D
KW - EAE
KW - Estrogen
KW - GPR30
UR - http://www.scopus.com/inward/record.url?scp=84861821689&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84861821689&partnerID=8YFLogxK
U2 - 10.1007/s11011-011-9266-6
DO - 10.1007/s11011-011-9266-6
M3 - Article
C2 - 21994003
AN - SCOPUS:84861821689
VL - 27
SP - 29
EP - 35
JO - Metabolic Brain Disease
JF - Metabolic Brain Disease
SN - 0885-7490
IS - 1
ER -