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 R.
AU - Vandenbark, Arthur A.
AU - Offner, Halina
PY - 2012/3/1
Y1 - 2012/3/1
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 -