Source:http://linkedlifedata.com/resource/pubmed/id/16543659
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2006-3-17
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pubmed:abstractText |
1 alpha,25-dihydroxyvitamin D3 [Calcitriol or 1,25(OH)(2)D(3)] is an important active metabolite involved in multiple functions but its calcemic effect in vivo limits its therapeutic applications. On the other hand, 22-oxa-1 alpha,25-dihydroxyvitamin D(3) (22-oxacalcitriol or 22-Oxa-1 alpha,25-D(3)), a low calcemic analog of vitamin D3 (VitD3), has been widely used as a drug for the secondary hyperparathyroidism. Here, we investigated immunomodulating effect of these two VitD3 derivatives on the differentiation of type-1 immunoregulatory cells such as dendritic cells (DC1), cytotoxic T cells (Tc1) and helper T cells (Th1). BALB/c mouse bone marrow-derived DC (BMDC1) induced by culture with Th1 condition (GM-CSF, IL-3, IL-12 and IFN-gamma) expressed higher levels of MHC Class I and Class II molecules and co-stimulatory molecules compared with BMDC0 induced by neutral condition (GM-CSF+IL-3). In addition, BMDC1 showed stronger immunostimulating activity to induce alloantigen (H-2(d))-specific cytotoxic T lymphocytes (CTL) compared with BMDC0. However, if VitD3 derivatives were added into the culture for BMDC1 induction, the expression of functional molecules and type-1 IFNs were greatly inhibited. Moreover, VitD3 derivative-treated BMDC1 lost their immunostimulating activity to induce alloantigen-specific IFN-gamma-producing Tc1. In addition, it was demonstrated that the addition of VitD3 derivatives inhibited the differentiation of IFN-gamma-producing Th1 cells from ovalbumin (OVA)-specific naive Th cells, while it rather augmented the differentiation of IL-4- or IL-10-producing Th2 cells. There was no significant difference in immunomodulating activity between 1,25(OH)(2)D(3) and 22-Oxa-1 alpha,25-D(3). Thus, VitD3 derivatives are demonstrated to inhibit the functional differentiation of DC1, Tc1 and Th1 cells, which play a critical role in type-1 cellular immune responses.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0388-6107
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
27
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1-9
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:16543659-Animals,
pubmed-meshheading:16543659-Antibodies, Monoclonal,
pubmed-meshheading:16543659-Bone Marrow Cells,
pubmed-meshheading:16543659-Cell Culture Techniques,
pubmed-meshheading:16543659-Cells, Cultured,
pubmed-meshheading:16543659-Cholecalciferol,
pubmed-meshheading:16543659-Cytotoxicity Tests, Immunologic,
pubmed-meshheading:16543659-Dendritic Cells,
pubmed-meshheading:16543659-Female,
pubmed-meshheading:16543659-Flow Cytometry,
pubmed-meshheading:16543659-Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:16543659-Immunity, Cellular,
pubmed-meshheading:16543659-Interleukin-3,
pubmed-meshheading:16543659-Mice,
pubmed-meshheading:16543659-Mice, Inbred BALB C,
pubmed-meshheading:16543659-Mice, Inbred C57BL,
pubmed-meshheading:16543659-Mice, Transgenic,
pubmed-meshheading:16543659-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:16543659-T-Lymphocytes, Cytotoxic,
pubmed-meshheading:16543659-Th1 Cells
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pubmed:year |
2006
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pubmed:articleTitle |
Immunomodulating effect of vitamin D3 derivatives on type-1 cellular immunity.
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pubmed:affiliation |
Division of Immunoregulation, Institute for Genetic Medicine, Hokkaido University, Sapparo, Japan.
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pubmed:publicationType |
Journal Article,
Comparative Study
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