Gender differences in 1,25 dihydroxyvitamin D3 immunomodulatory effects in multiple sclerosis patients and healthy subjects
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...
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2010
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v185_n8_p4948_Correale http://hdl.handle.net/20.500.12110/paper_00221767_v185_n8_p4948_Correale |
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paper:paper_00221767_v185_n8_p4948_Correale2023-06-08T14:46:57Z Gender differences in 1,25 dihydroxyvitamin D3 immunomodulatory effects in multiple sclerosis patients and healthy subjects 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 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. 2010 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v185_n8_p4948_Correale http://hdl.handle.net/20.500.12110/paper_00221767_v185_n8_p4948_Correale |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Gender differences in 1,25 dihydroxyvitamin D3 immunomodulatory effects in multiple sclerosis patients and healthy subjects |
| topic_facet |
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 |
| description |
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. |
| title |
Gender differences in 1,25 dihydroxyvitamin D3 immunomodulatory effects in multiple sclerosis patients and healthy subjects |
| title_short |
Gender differences in 1,25 dihydroxyvitamin D3 immunomodulatory effects in multiple sclerosis patients and healthy subjects |
| title_full |
Gender differences in 1,25 dihydroxyvitamin D3 immunomodulatory effects in multiple sclerosis patients and healthy subjects |
| title_fullStr |
Gender differences in 1,25 dihydroxyvitamin D3 immunomodulatory effects in multiple sclerosis patients and healthy subjects |
| title_full_unstemmed |
Gender differences in 1,25 dihydroxyvitamin D3 immunomodulatory effects in multiple sclerosis patients and healthy subjects |
| title_sort |
gender differences in 1,25 dihydroxyvitamin d3 immunomodulatory effects in multiple sclerosis patients and healthy subjects |
| publishDate |
2010 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v185_n8_p4948_Correale http://hdl.handle.net/20.500.12110/paper_00221767_v185_n8_p4948_Correale |
| _version_ |
1768543216067411968 |