Source:http://linkedlifedata.com/resource/pubmed/id/17551101
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
|
| pubmed:dateCreated |
2007-10-1
|
| pubmed:abstractText |
We have previously reported that 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3) can selectively suppress key functions of interferon-gamma (IFN-gamma) activated macrophages. To further explore this mechanism for its relevance in vivo, we investigated an infection model that crucially depends on the function of IFN-gamma activated macrophages, the infection with the intracellular protozoan Leishmania major. 1Alpha,25(OH)2D3 treatment of L. major infected macrophages demonstrated a vitamin D receptor (Vdr) dependent inhibition of macrophage killing activity. Further analysis showed that this was a result of decreased production of nitric oxide by 1alpha,25(OH)2D3-treated macrophages due to Vdr-dependent up-regulation of arginase 1 expression, which overrides NO production by Nos2. When analyzing the course of infection in vivo, we found that Vdr-knockout (Vdr-KO) mice were more resistant to L. major infection than their wild-type littermates. This result is in agreement with an inhibitory influence of 1alpha,25(OH)2D3 on the macrophage mediated host defense. Further investigation showed that Vdr-KO mice developed an unaltered T helper cell type 1 (Th1) response on infection as indicated by normal production of IFN-gamma by CD4+ and CD8+ T cells. Therefore, we propose that the absence of 1alpha,25(OH)2D3-mediated inhibition of macrophage microbicidal activity in Vdr-KO mice results in increased resistance to Leishmania infection.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Arginase,
http://linkedlifedata.com/resource/pubmed/chemical/Calcitriol,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type II,
http://linkedlifedata.com/resource/pubmed/chemical/Nos2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Calcitriol
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
|
| pubmed:issn |
1530-6860
|
| pubmed:author | |
| pubmed:issnType |
Electronic
|
| pubmed:volume |
21
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
3208-18
|
| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading |
pubmed-meshheading:17551101-Animals,
pubmed-meshheading:17551101-Arginase,
pubmed-meshheading:17551101-Calcitriol,
pubmed-meshheading:17551101-Cytokines,
pubmed-meshheading:17551101-Disease Susceptibility,
pubmed-meshheading:17551101-Humans,
pubmed-meshheading:17551101-Interferon-gamma,
pubmed-meshheading:17551101-Leishmania major,
pubmed-meshheading:17551101-Leishmaniasis, Cutaneous,
pubmed-meshheading:17551101-Macrophages,
pubmed-meshheading:17551101-Mice,
pubmed-meshheading:17551101-Mice, Inbred C57BL,
pubmed-meshheading:17551101-Mice, Knockout,
pubmed-meshheading:17551101-Nitric Oxide,
pubmed-meshheading:17551101-Nitric Oxide Synthase Type II,
pubmed-meshheading:17551101-Phagocytosis,
pubmed-meshheading:17551101-Receptors, Calcitriol,
pubmed-meshheading:17551101-Signal Transduction,
pubmed-meshheading:17551101-T-Lymphocytes
|
| pubmed:year |
2007
|
| pubmed:articleTitle |
Vitamin D receptor signaling contributes to susceptibility to infection with Leishmania major.
|
| pubmed:affiliation |
Institute for Experimental Dermatology, University of Münster, Münster, Germany.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|