|Expression of vitamin D receptor and metabolizing enzymes in multiple sclerosis-affected brain tissue.|
|PMID: 23334593 Owner: NLM Status: MEDLINE|
|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.|
|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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|Type: Journal Article; Research Support, Non-U.S. Gov't|
|Title: Journal of neuropathology and experimental neurology Volume: 72 ISSN: 1554-6578 ISO Abbreviation: J. Neuropathol. Exp. Neurol. Publication Date: 2013 Feb|
|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|
|Languages: eng Pagination: 91-105 Citation Subset: IM|
|APA/MLA Format Download EndNote Download BibTex|
25-Hydroxyvitamin D3 1-alpha-Hydroxylase
Aged, 80 and over
Astrocytes / drug effects, metabolism
Astrocytoma / pathology
Brain / metabolism*, pathology
Corpus Callosum / pathology
Gene Expression Regulation* / drug effects
Glial Fibrillary Acidic Protein / metabolism
Interferon-gamma / pharmacology
Kidney / metabolism
Liver / metabolism
Multiple Sclerosis / enzymology, genetics, metabolism*, pathology*
Nerve Fibers, Myelinated / metabolism, pathology
Neuroblastoma / pathology
Neurons / drug effects, metabolism
Receptors, Calcitriol / metabolism*
Steroid Hydroxylases / genetics, metabolism*
Tumor Necrosis Factor-alpha / pharmacology
Up-Regulation / drug effects
Vitamin D / pharmacology
|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 22.214.171.124/vitamin D 24-hydroxylase|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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