| 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. | |
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MedLine Citation:
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PMID: 20930170 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Masafumi Takeda; Tomoya Yamashita; Naoto Sasaki; Kenji Nakajima; Tomoyuki Kita; Masakazu Shinohara; Tatsuro Ishida; Ken-ichi Hirata |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-07 |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 30 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-18 Completed Date: 2010-12-21 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States |
Other Details:
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Languages: eng Pagination: 2495-503 Citation Subset: IM |
Affiliation:
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Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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:
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Arterioscler Thromb Vasc Biol. 2010 Dec;30(12):2317-9
[PMID:
21084698
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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