PMID- 23334593
OWN - NLM
STAT- MEDLINE
DCOM- 20130311
LR  - 20220321
IS  - 1554-6578 (Electronic)
IS  - 0022-3069 (Linking)
VI  - 72
IP  - 2
DP  - 2013 Feb
TI  - Expression of vitamin D receptor and metabolizing enzymes in multiple 
      sclerosis-affected brain tissue.
PG  - 91-105
LID - 10.1097/NEN.0b013e31827f4fcc [doi]
AB  - Vitamin D deficiency has been implicated as a risk factor for multiple sclerosis 
      (MS), but how vitamin D metabolism affects MS pathophysiology is not understood. 
      We studied the expression of vitamin D receptor (VDR) and related enzymes, 
      including 1,25(OH)(2)D-24-hydroxylase (24-OHase; CYP24A1) and 
      25(OH)D-1alpha-hydroxylase (CYP27B1), in CNS tissues of 39 MS patients and 20 
      controls and in primary human glial cells in vitro. In control and MS 
      normal-appearing white matter (NAWM), nuclear VDR immunostaining was observed in 
      oligodendrocyte-like cells, human leukocyte antigen (HLA)-positive microglia, and 
      glial fibrillary acidic protein-positive astrocytes. There was a 2-fold increase 
      in VDR transcripts in MS NAWM versus control white matter (p = 0.03). In chronic 
      active MS lesions, HLA-positive microglia/macrophages showed nuclear VDR 
      staining; astrocytes showed nuclear and cytoplasmic VDR staining. Staining for 
      24-OHase was restricted to astrocytes.VDR and CYP27B1 mRNA expressions were 
      increased in active MS lesions versus NAWM (p < 0.01, p = 0.04, respectively). In 
      primary human astrocytes in vitro, the active form of vitamin D, 1,25(OH)(2)D(3), 
      induced upregulation of VDR and CYP24A1. Tumor necrosis factor and interferon-gamma 
      upregulated CYP27B1 mRNA in primary human microglia and astrocytes. Increased VDR 
      expression in MS NAWM and inflammatory cytokine-induced amplified expression of 
      VDR and CYP27B1 in chronic active MS lesions suggest increased sensitivity to 
      vitamin D in NAWM and a possible endogenous role for vitamin D metabolism in the 
      suppression of active MS lesions.
FAU - Smolders, Joost
AU  - Smolders J
AD  - Neuroimmunology Research Group, Netherlands Institute for Neuroscience, 
      Amsterdam, The Netherlands. smolders@gmail.com
FAU - Schuurman, Karianne G
AU  - Schuurman KG
FAU - van Strien, Miriam E
AU  - van Strien ME
FAU - Melief, Jeroen
AU  - Melief J
FAU - Hendrickx, Debbie
AU  - Hendrickx D
FAU - Hol, Elly M
AU  - Hol EM
FAU - van Eden, Corbert
AU  - van Eden C
FAU - Luchetti, Sabina
AU  - Luchetti S
FAU - Huitinga, Inge
AU  - Huitinga I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neuropathol Exp Neurol
JT  - Journal of neuropathology and experimental neurology
JID - 2985192R
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 1406-16-2 (Vitamin D)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 1.14.- (Steroid Hydroxylases)
RN  - EC 1.14.15.16 (CYP24A1 protein, human)
RN  - EC 1.14.15.16 (Vitamin D3 24-Hydroxylase)
RN  - EC 1.14.15.18 (25-Hydroxyvitamin D3 1-alpha-Hydroxylase)
SB  - IM
MH  - 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics/*metabolism
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Astrocytes/drug effects/metabolism
MH  - Astrocytoma/pathology
MH  - Brain/*metabolism/pathology
MH  - Cells, Cultured
MH  - Cohort Studies
MH  - Corpus Callosum/pathology
MH  - Female
MH  - *Gene Expression Regulation/drug effects
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Humans
MH  - Interferon-gamma/pharmacology
MH  - Kidney/metabolism
MH  - Liver/metabolism
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis/enzymology/genetics/*metabolism/*pathology
MH  - Nerve Fibers, Myelinated/metabolism/pathology
MH  - Netherlands
MH  - Neuroblastoma/pathology
MH  - Neurons/drug effects/metabolism
MH  - RNA, Messenger
MH  - Receptors, Calcitriol/*metabolism
MH  - Statistics, Nonparametric
MH  - Steroid Hydroxylases/genetics/*metabolism
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Up-Regulation/drug effects
MH  - Vitamin D/pharmacology
MH  - Vitamin D3 24-Hydroxylase
EDAT- 2013/01/22 06:00
MHDA- 2013/03/12 06:00
CRDT- 2013/01/22 06:00
PHST- 2013/01/22 06:00 [entrez]
PHST- 2013/01/22 06:00 [pubmed]
PHST- 2013/03/12 06:00 [medline]
AID - 00005072-201302000-00003 [pii]
AID - 10.1097/NEN.0b013e31827f4fcc [doi]
PST - ppublish
SO  - J Neuropathol Exp Neurol. 2013 Feb;72(2):91-105. doi: 
      10.1097/NEN.0b013e31827f4fcc.