Abstract |
We report here that curative treatment of the multiple sclerosis paradigm, chronic relapsing experimental autoimmune encephalomyelitis (EAE) of the Lewis rat, by 1,25-dihydroxyvitamin D(3 )(1,25-D3) leads to a rapid clinical improvement accompanied by an inhibition of CD4, MHC class II and type II nitric oxide synthase ( NOS II) expression in the posterior areas of the central nervous system (CNS). In contrast, the hormone has no effect on transforming growth factor-beta1 transcripts. Computer analysis of the NOS II promoter, expressed by microglia and astrocytes, reveals consensus sequence for vitamin D receptor binding, emphasizing the idea that 1,25-D3 may regulate some aspects of EAE by acting directly on CNS constituent cells. We also demonstrate that vitamin D deprivation leads to minimal effects on the kinetic profile of EAE accompanied by a moderate exacerbation of the clinical symptoms. Interestingly, curative treatment of vitamin D-deprived rats with a non-toxic-1,25-D3 analogue ( MC1288) strongly inhibited EAE symptoms, thus promulgating the potential interest of such compounds in the management of multiple sclerosis.
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Authors | Emmanuel Garcion, Laurence Sindji, Serge Nataf, Philippe Brachet, Françoise Darcy, Claudia N Montero-Menei |
Journal | Acta neuropathologica
(Acta Neuropathol)
Vol. 105
Issue 5
Pg. 438-48
(May 2003)
ISSN: 0001-6322 [Print] Germany |
PMID | 12677443
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Bacterial Proteins
- CD4 Antigens
- Calcium Channel Agonists
- Macrophage-1 Antigen
- Map protein, Staphylococcus aureus
- RNA, Messenger
- Tgfb1 protein, rat
- Transforming Growth Factor beta
- Transforming Growth Factor beta1
- Nitric Oxide Synthase
- Nitric Oxide Synthase Type II
- Calcitriol
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Topics |
- Animals
- Bacterial Proteins
(metabolism)
- Brain Mapping
- CD4 Antigens
(metabolism)
- Calcitriol
(pharmacology, therapeutic use)
- Calcium Channel Agonists
(therapeutic use)
- Case-Control Studies
- Central Nervous System
(drug effects, metabolism)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Encephalomyelitis, Autoimmune, Experimental
(chemically induced, drug therapy)
- Female
- Immunohistochemistry
(methods)
- In Situ Hybridization
(methods)
- Macrophage-1 Antigen
(drug effects, metabolism)
- Nitric Oxide Synthase
(genetics, metabolism)
- Nitric Oxide Synthase Type II
- Promoter Regions, Genetic
- RNA, Messenger
(biosynthesis)
- Rats
- Rats, Inbred Lew
- Sequence Analysis
- Transforming Growth Factor beta
(genetics)
- Transforming Growth Factor beta1
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