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Abstract:

Vitamin D3 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 D3 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 D3-binding protein, a transporter for vitamin D 3 and its metabolites. These gender-based disparities lead to the accumulation of vitamin D3 and its metabolites in target cells from female subjects and result in a more potent antiinflammatory 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 D3 and 17-β estradiol, mediated through estrogen receptor α. Collectively, these results demonstrate estrogen-promoted differences in vitamin D metabolism, suggesting a greater protective effect of vitamin D3-based therapeutic strategies in women. Copyright © 2010 by The American Association of Immunologists, Inc.

Registro:

Documento: Artículo
Título:Gender differences in 1,25 dihydroxyvitamin D3 immunomodulatory effects in multiple sclerosis patients and healthy subjects
Autor:Correale, J.; Ysrraelit, M.C.; Gaitan, M.I.
Filiación:Department of Neurology, Raúl Carrea Institute for Neurological Research, Montañeses 2325, 1428 Buenos Aires, Argentina
Palabras clave:binding protein; calcitriol; estradiol; estrogen receptor alpha; gamma interferon; interleukin 10; interleukin 17; transcription factor FOXP3; calcitriol; cytokine; estradiol; estrogen; estrogen receptor; immunologic factor; adult; antiinflammatory activity; article; binding affinity; CD4+ CD25+ T lymphocyte; cell proliferation; controlled study; female; human; human cell; immunomodulation; inhibition kinetics; internalization; macrophage; major clinical study; male; multiple sclerosis; priority journal; regulatory T lymphocyte; RNA transcription; secretory cell; sex difference; T lymphocyte; vitamin D metabolism; biosynthesis; blood; drug effect; enzyme linked immunosorbent assay; immunology; metabolism; reverse transcription polymerase chain reaction; sexual development; Adult; Calcitriol; Cell Proliferation; Cytokines; Enzyme-Linked Immunosorbent Assay; Estradiol; Estrogens; Female; Humans; Immunologic Factors; Male; Multiple Sclerosis, Relapsing-Remitting; Receptors, Estrogen; Reverse Transcriptase Polymerase Chain Reaction; Sex Characteristics; T-Lymphocytes
Año:2010
Volumen:185
Número:8
Página de inicio:4948
Página de fin:4958
DOI: http://dx.doi.org/10.4049/jimmunol.1000588
Título revista:Journal of Immunology
Título revista abreviado:J. Immunol.
ISSN:00221767
CODEN:JOIMA
CAS:calcitriol, 32222-06-3, 32511-63-0, 66772-14-3; estradiol, 50-28-2; gamma interferon, 82115-62-6; Calcitriol, 32222-06-3; Cytokines; Estradiol, 50-28-2; Estrogens; Immunologic Factors; Receptors, Estrogen
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v185_n8_p4948_Correale

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Citas:

---------- APA ----------
Correale, J., Ysrraelit, M.C. & Gaitan, M.I. (2010) . Gender differences in 1,25 dihydroxyvitamin D3 immunomodulatory effects in multiple sclerosis patients and healthy subjects. Journal of Immunology, 185(8), 4948-4958.
http://dx.doi.org/10.4049/jimmunol.1000588
---------- CHICAGO ----------
Correale, J., Ysrraelit, M.C., Gaitan, M.I. "Gender differences in 1,25 dihydroxyvitamin D3 immunomodulatory effects in multiple sclerosis patients and healthy subjects" . Journal of Immunology 185, no. 8 (2010) : 4948-4958.
http://dx.doi.org/10.4049/jimmunol.1000588
---------- MLA ----------
Correale, J., Ysrraelit, M.C., Gaitan, M.I. "Gender differences in 1,25 dihydroxyvitamin D3 immunomodulatory effects in multiple sclerosis patients and healthy subjects" . Journal of Immunology, vol. 185, no. 8, 2010, pp. 4948-4958.
http://dx.doi.org/10.4049/jimmunol.1000588
---------- VANCOUVER ----------
Correale, J., Ysrraelit, M.C., Gaitan, M.I. Gender differences in 1,25 dihydroxyvitamin D3 immunomodulatory effects in multiple sclerosis patients and healthy subjects. J. Immunol. 2010;185(8):4948-4958.
http://dx.doi.org/10.4049/jimmunol.1000588