Source:http://linkedlifedata.com/resource/pubmed/id/18056481
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2008-2-27
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pubmed:abstractText |
Crystalline silica exposure can result in pulmonary fibrosis, where the pulmonary macrophage is key as a result of its ability to react to silica particles. In the mouse silicosis model, there is initial Th1-type inflammation, characterized by TNF-alpha and IFN-gamma. Previous studies determined that Th2 mediators (i.e., IL-13) are vital to development of pulmonary fibrosis. The present study, using in vivo and in vitro techniques, compares silica exposures between Balb/c and Th2-deficient mice in an effort to determine the link between Th2 immunity and silicosis. In long-term experiments, a significant increase in fibrosis and activated interstitial macrophages was observed in Balb/c but not IL-4Ralpha(-/-) mice. Additionally, a significant increase in Ym1 mRNA levels, a promoter of Th2 immunity, was determined in the interstitial leukocyte population of silica-exposed Balb/c mice. To elucidate the effects of silica on macrophage function, bone marrow-derived macrophages (BMdM) were exposed to particles and assayed for T cell (TC) stimulation activity. As a control, Ym1 mRNA expression in Balb/c BMdM was determined using IL-4 stimulation. In the in vitro assay, a significant increase in TC activation, as defined by surface markers and cytokines, was observed in the cultures containing the silica-exposed macrophages in wild-type and IL-4Ralpha(-/-) mice, with one exception: IL-4Ralpha(-/-) BMdM were unable to induce an increase in IL-13. These results suggest that crystalline silica alters cellular functions of macrophages, including activation of TC, and that the increase in Th2 immunity associated with silicosis is via the IL-4Ralpha-Ym1 pathway.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Collagen,
http://linkedlifedata.com/resource/pubmed/chemical/Il4ra protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Silicon Dioxide
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0741-5400
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
83
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
630-9
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pubmed:meshHeading |
pubmed-meshheading:18056481-Animals,
pubmed-meshheading:18056481-Antigen-Presenting Cells,
pubmed-meshheading:18056481-Cell Division,
pubmed-meshheading:18056481-Collagen,
pubmed-meshheading:18056481-Flow Cytometry,
pubmed-meshheading:18056481-Lymphocyte Activation,
pubmed-meshheading:18056481-Macrophages,
pubmed-meshheading:18056481-Mice,
pubmed-meshheading:18056481-Mice, Inbred BALB C,
pubmed-meshheading:18056481-Mice, Knockout,
pubmed-meshheading:18056481-Polymerase Chain Reaction,
pubmed-meshheading:18056481-Pulmonary Fibrosis,
pubmed-meshheading:18056481-RNA, Messenger,
pubmed-meshheading:18056481-Receptors, Cell Surface,
pubmed-meshheading:18056481-Silicon Dioxide,
pubmed-meshheading:18056481-T-Lymphocytes
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pubmed:year |
2008
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pubmed:articleTitle |
The IL-4Ralpha pathway in macrophages and its potential role in silica-induced pulmonary fibrosis.
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pubmed:affiliation |
Center for Environmental Health Sciences, University of Montana, Missoula, MT 59812, USA. christopher.migliaccio@umontana.edu
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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