| Human dendritic cell antigen presentation and chemotaxis are inhibited by intrinsic 25-hydroxy vitamin D activation. | |
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MedLine Citation:
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PMID: 20483384 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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The immunomodulatory effects of vitamin D have primarily been investigated using the biologically active form 1,25-dihydroxy vitamin D3 (1,25-D3). It was recently demonstrated that dendritic cells (DC) are able to convert the inactive 25-hydroxy vitamin D3 (25-D3) into the active form via 1 alpha-hydroxylase. In this study, we set out to examine the possible consequences of this conversion on adaptive immune functions. Human monocyte-derived DC were matured by lipopolysaccharide (LPS) in the presence or absence of 25-D3. Subsequently, the conversion of 25-D3 into 1,25-D3, and the effects on surface marker expression, cytokine production, antigen-presenting capacity and chemotaxis of the DC were examined. 25-D3 was clearly converted into 1,25-D3 in the DC cultures and the process was accompanied by a reduced expression of CD80 (p<0.01), CD83 (p<0.01), CD86 (p=0.02), and HLA-DR (p=0.02). Also, the levels of the pro-inflammatory cytokines tumour necrosis factor (TNF) alpha (p=0.02) and interleukin (IL) 12 (p<0.01) were reduced. Interestingly, however, the CD14 expression (p<0.01) and the production of IL-1 beta (p<0.01) and IL-6 (p<0.01) increased. Thus, 25-D3 affected the delicate interplay between anti- and pro-inflammatory cytokines produced by the DC. Concurrently, 25-D3 reduced DC capacity to induce proliferation of antigen-specific T cells and DC chemotaxis towards chemokine (CC) ligand 21. This indicates that 25-D3 has a regulating function following intrinsic 1 alpha-hydroxylation, a mechanism that potentially has an immunomodulatory effect in vivo. |
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Authors:
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Lars E Bartels; Christian L Hvas; Jørgen Agnholt; Jens F Dahlerup; Ralf Agger |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-05-17 |
Journal Detail:
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Title: International immunopharmacology Volume: 10 ISSN: 1878-1705 ISO Abbreviation: Int. Immunopharmacol. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-21 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100965259 Medline TA: Int Immunopharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 922-8 Citation Subset: IM |
Copyright Information:
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(c) 2010 Elsevier B.V. All rights reserved. |
Affiliation:
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Laboratory of Immunology, Aalborg University, Fredrik Bajers Vej 3B, 9220 Aalborg Ø, Denmark. bartels@ki.au.dk |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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