Document Detail


Oral administration of an active form of vitamin D3 (calcitriol) decreases atherosclerosis in mice by inducing regulatory T cells and immature dendritic cells with tolerogenic functions.
MedLine Citation:
PMID:  20930170     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To determine whether the administration of an active form of vitamin D(3) (calcitriol) could prevent atherosclerosis through anti-inflammatory actions.
METHODS AND RESULTS: Recent clinical studies have shown that lack of vitamin D(3) is a risk factor for cardiovascular events. Oral calcitriol administration decreased atherosclerotic lesions, macrophage accumulation, and CD4(+) T-cell infiltration at the aortic sinus, when compared with the corresponding observations in control mice. We observed a significant increase in Foxp3(+) regulatory T cells and a decrease in CD80(+)CD86(+) dendritic cells (DCs) in the mesenteric lymph nodes, spleen, and atherosclerotic lesions in oral calcitriol-treated mice in association with increased interleukin 10 and decreased interleukin 12 mRNA expression. CD11c(+) DCs from the calcitriol group showed reduced proliferative activity of T lymphocytes, suggesting the suppression of DC maturation. Neutralization of CD25 in vivo revealed that calcitriol inhibited atherosclerosis mainly in a regulatory T cell-dependent manner but also partly because of a decrease in DC maturation.
CONCLUSIONS: Oral calcitriol treatment could prevent the development of atherosclerosis by changing the function or differentiation of DCs and regulatory T cells. These findings suggest that intestinal and systemic immune modulation by calcitriol may be a potentially valuable therapeutic approach against atherosclerosis.
Authors:
Masafumi Takeda; Tomoya Yamashita; Naoto Sasaki; Kenji Nakajima; Tomoyuki Kita; Masakazu Shinohara; Tatsuro Ishida; Ken-ichi Hirata
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-07
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  30     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-18     Completed Date:  2010-12-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2495-503     Citation Subset:  IM    
Affiliation:
Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Animals
Anti-Inflammatory Agents / administration & dosage*
Antigens, CD11c / metabolism
Antigens, CD80 / metabolism
Antigens, CD86 / metabolism
Aortic Diseases / genetics,  immunology,  pathology,  prevention & control*
Apolipoproteins E / deficiency,  genetics
Atherosclerosis / genetics,  immunology,  pathology,  prevention & control*
Calcitriol / administration & dosage*
Cells, Cultured
Dendritic Cells / drug effects*,  immunology
Disease Models, Animal
Female
Forkhead Transcription Factors / metabolism
Gene Expression Regulation
Immune Tolerance / drug effects*,  genetics
Inflammation Mediators / metabolism
Interleukin-10 / genetics
Interleukin-12 / genetics
Interleukin-2 Receptor alpha Subunit / metabolism
Intestine, Small / drug effects*,  immunology
Lymph Nodes / drug effects,  immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
RNA, Messenger / metabolism
Spleen / drug effects,  immunology
T-Lymphocytes, Regulatory / drug effects*,  immunology
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Antigens, CD11c; 0/Antigens, CD80; 0/Antigens, CD86; 0/Apolipoproteins E; 0/Cd86 protein, mouse; 0/Forkhead Transcription Factors; 0/Foxp3 protein, mouse; 0/Il2ra protein, mouse; 0/Inflammation Mediators; 0/Interleukin-2 Receptor alpha Subunit; 0/RNA, Messenger; 130068-27-8/Interleukin-10; 187348-17-0/Interleukin-12; 32222-06-3/Calcitriol
Comments/Corrections
Comment In:
Arterioscler Thromb Vasc Biol. 2010 Dec;30(12):2317-9   [PMID:  21084698 ]

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