Document Detail


Expression of vitamin D receptor and metabolizing enzymes in multiple sclerosis-affected brain tissue.
MedLine Citation:
PMID:  23334593     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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-1α-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-γ 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.
Authors:
Joost Smolders; Karianne G Schuurman; Miriam E van Strien; Jeroen Melief; Debbie Hendrickx; Elly M Hol; Corbert van Eden; Sabina Luchetti; Inge Huitinga
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neuropathology and experimental neurology     Volume:  72     ISSN:  1554-6578     ISO Abbreviation:  J. Neuropathol. Exp. Neurol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-21     Completed Date:  2013-03-11     Revised Date:  2014-01-13    
Medline Journal Info:
Nlm Unique ID:  2985192R     Medline TA:  J Neuropathol Exp Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  91-105     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics,  metabolism*
Adult
Aged
Aged, 80 and over
Astrocytes / drug effects,  metabolism
Astrocytoma / pathology
Brain / metabolism*,  pathology
Cells, Cultured
Cohort Studies
Corpus Callosum / pathology
Female
Gene Expression Regulation* / drug effects
Glial Fibrillary Acidic Protein / metabolism
Humans
Interferon-gamma / pharmacology
Kidney / metabolism
Liver / metabolism
Male
Middle Aged
Multiple Sclerosis / enzymology,  genetics,  metabolism*,  pathology*
Nerve Fibers, Myelinated / metabolism,  pathology
Netherlands
Neuroblastoma / pathology
Neurons / drug effects,  metabolism
RNA, Messenger
Receptors, Calcitriol / metabolism*
Statistics, Nonparametric
Steroid Hydroxylases / genetics,  metabolism*
Tumor Necrosis Factor-alpha / pharmacology
Up-Regulation / drug effects
Vitamin D / pharmacology
Chemical
Reg. No./Substance:
0/Glial Fibrillary Acidic Protein; 0/RNA, Messenger; 0/Receptors, Calcitriol; 0/Tumor Necrosis Factor-alpha; 1406-16-2/Vitamin D; 82115-62-6/Interferon-gamma; EC 1.14.-/25-Hydroxyvitamin D3 1-alpha-Hydroxylase; EC 1.14.-/Steroid Hydroxylases; EC 1.14.13.126/vitamin D 24-hydroxylase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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