title: Treatment of experimental autoimmune encephalomyelitis in rat by 1,25-dihydroxyvitamin D3 leads to early effects within the central nervous system.
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.
authors.affiliation: INSERM ERIT-M 0104, 10 rue André Boquel, 49100 Angers, France. emmanuel.garcion@univ-angers.fr
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Garcion
authors.forename: Laurence
authors.initials: L
authors.lastname: Sindji
authors.forename: Serge
authors.initials: S
authors.lastname: Nataf
authors.forename: Philippe
authors.initials: P
authors.lastname: Brachet
authors.forename: Françoise
authors.initials: F
authors.lastname: Darcy
authors.forename: Claudia N
authors.initials: CN
authors.lastname: Montero-Menei
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D001931:Brain Mapping; D015704:CD4 Antigens / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology / Q000627:therapeutic use*; D002120:Calcium Channel Agonists / Q000627:therapeutic use*; D016022:Case-Control Studies; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D016177:Macrophage-1 Antigen / Q000187:drug effects / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D017421:Sequence Analysis; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1
chemical_list: D001426:Bacterial Proteins; D015704:CD4 Antigens; D002120:Calcium Channel Agonists; D016177:Macrophage-1 Antigen; C095564:Map protein, Staphylococcus aureus; D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D002117:Calcitriol