Document Detail


Gender differences in 1,25 dihydroxyvitamin D3 immunomodulatory effects in multiple sclerosis patients and healthy subjects.
MedLine Citation:
PMID:  20855882     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Vitamin D(3) is best known as a calcium homeostasis modulator; however, it also has immune-modulating potential. In this study, we demonstrated that immunomodulatory effects of vitamin D(3) are significantly stronger in females than in males in multiple sclerosis patients, as well as in healthy subjects. Inhibition of self-reactive T cell proliferation and reduction in IFN-γ- and IL-17-secreting cell numbers were considerably greater in females. Furthermore, the increase in IL-10-secreting and CD4(+)CD25(+)FoxP3(+) regulatory T cell numbers were also greater in females. In parallel with these findings, female subjects had fewer CYP24A1 transcripts encoding the 1,25-dihydroxyvitamin D(3)-inactivating enzyme, as well as greater binding and internalization of vitamin D(3)-binding protein, a transporter for vitamin D(3) and its metabolites. These gender-based disparities lead to the accumulation of vitamin D(3) and its metabolites in target cells from female subjects and result in a more potent anti-inflammatory effect. Interestingly, 17-β estradiol reproduced these effects on self-reactive T cells and macrophages from male subjects, suggesting a functional synergy between 1,25-dihydroxyvitamin D(3) and 17-β estradiol, mediated through estrogen receptor α. Collectively, these results demonstrate estrogen-promoted differences in vitamin D(3) metabolism, suggesting a greater protective effect of vitamin D(3)-based therapeutic strategies in women.
Authors:
Jorge Correale; María C Ysrraelit; María I Gaitán
Publication Detail:
Type:  Journal Article     Date:  2010-09-20
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  185     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-06     Completed Date:  2010-11-04     Revised Date:  2011-01-21    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4948-58     Citation Subset:  AIM; IM    
Affiliation:
Department of Neurology, Raúl Carrea Institute for Neurological Research, Buenos Aires, Argentina. jcorreale@fleni.org.ar
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MeSH Terms
Descriptor/Qualifier:
Adult
Calcitriol / blood,  metabolism,  pharmacology*
Cell Proliferation / drug effects
Cytokines / biosynthesis
Enzyme-Linked Immunosorbent Assay
Estradiol / pharmacology
Estrogens / pharmacology
Female
Humans
Immunologic Factors / blood,  metabolism,  pharmacology*
Male
Multiple Sclerosis, Relapsing-Remitting / immunology*,  metabolism*
Receptors, Estrogen / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Sex Characteristics*
T-Lymphocytes / drug effects,  immunology
Chemical
Reg. No./Substance:
0/Cytokines; 0/Estrogens; 0/Immunologic Factors; 0/Receptors, Estrogen; 32222-06-3/Calcitriol; 50-28-2/Estradiol
Comments/Corrections
Comment In:
J Immunol. 2011 Jan 15;186(2):647; author reply 648   [PMID:  21209286 ]

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


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