| Influence of 1,25-dihydroxy vitamin D3 on TLR4-induced activation of antigen presenting cells is dependent on the order of receptor engagement. | |
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MedLine Citation:
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PMID: 21529994 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The vitamin D metabolite, 1,25-(OH)(2)D(3), binds the vitamin D receptor (VDR) to exert its regulatory effects at the transcription level. VDR is expressed in professional antigen-presenting cells (pAPCs), such as macrophages (Mø) and dendritic cells (DCs). We show for the first time that the 24-hydroxylase enzyme is activated in bone marrow-derived dendritic cell (BMDC), due to 1,25(OH)(2)D(3) stimulation which resulted in the induction of its gene, CYP24A1. Furthermore, we provide evidence that the influence of 1,25-(OH)(2)D(3) on TLR-4-L-induced activation of pAPC is dependent on the order of VDR and TLR-4 engagement. Thus, pre-treatment of pAPC with 1,25-(OH)(2)D(3) partially inhibited LPS-induced nitric oxide (NO) production. However, these inhibitory effects were not observed when LPS and 1,25-(OH)(2)D(3) were added simultaneously or when LPS preceded 1,25-(OH)(2)D(3). Moreover, we found that 1,25-(OH)(2)D(3) pre-treatment of pAPCs did not cause general suppression since it interfered with NO levels but not with the cytokines IL-6 or TNF-α. Consequently, engagement of VDR by 1,25-(OH)(2)D(3) can partially interfere with TLR-4-L-induced activation of pAPCs only when it occurs before TLR-4 stimulation. |
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Authors:
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Vandana Gambhir; Julia Kim; Sarah Siddiqui; Michelle Taylor; Valarie Byford; Elaine O Petrof; Glenville Jones; Sameh Basta |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-4-7 |
Journal Detail:
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Title: Immunobiology Volume: - ISSN: 1878-3279 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-5-2 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8002742 Medline TA: Immunobiology Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier GmbH. |
Affiliation:
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Department of Microbiology and Immunology, Queen's University, Kingston, Ontario, Canada. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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