Source:http://linkedlifedata.com/resource/pubmed/id/12193738
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2002-8-23
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pubmed:abstractText |
The p40 subunit of IL-12 (IL-12p40), but not the heterodimeric form IL-12p70, is secreted during the development of silica-induced lung fibrosis in C57BL/6 mice. To delineate the contribution of IL-12p40 to the lung inflammatory and fibrotic processes, we compared the pulmonary responses with silica particles of IL-12p35-deficient mice (IL-12p35(-/-), able to produce IL-12p40) and IL-12p40-deficient mice (IL-12p40(-/-)). IL-12p35(-/-) and IL-12p40(-/-) animals developed strikingly contrasting responses to silica in comparison with wild-type C57BL/6 mice. Although the IL-12p40(-/-) mice exhibited limited inflammatory and fibrotic reactions, the IL-12p35(-/-) mice presented a robust and well-developed pulmonary inflammation and fibrosis. Furthermore, the silica-induced increase in lung IL-12p40 content was significantly higher in IL-12p35(-/-) mice than in wild-type controls, and was associated with extensive lung fibrosis and pulmonary macrophage infiltration. The contrasting responses observed between these two IL-12 subunit-deficient murine strains were not accompanied by a strict type 1 or type 2 polarization as estimated by the measurements of lung IFN-gamma/IgG2a and IL-4/IgG1 content. In vitro proliferation, type I collagen expression, as well as myofibroblast differentiation of purified pulmonary fibroblasts were not affected by treatment with exogenous rIL-12p40. In vivo, supplementation with rIL-12p40 restored the impaired pulmonary fibrotic response and macrophage accumulation in silica-treated IL-12p40(-/-) mice, and also promoted fibrosis and macrophage influx in wild-type mice. Together, our data suggest that IL-12p40 plays an important role in silica-induced pulmonary inflammation and fibrosis, possibly by exacerbating macrophage recruitment.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-12,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-12 Subunit p40,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Subunits,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Silicon Dioxide
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0022-1767
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pubmed:author |
pubmed-author:ArrasMohammedM,
pubmed-author:BarbarinVirginieV,
pubmed-author:CoutelierJean-PaulJP,
pubmed-author:DelosMoniqueM,
pubmed-author:HuauxFrancoisF,
pubmed-author:LisonDominiqueD,
pubmed-author:PhanSem HSH,
pubmed-author:RenauldJean-ChristopheJC,
pubmed-author:TomasiDavidD,
pubmed-author:VinkAnneA
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
169
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2653-61
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:12193738-Animals,
pubmed-meshheading:12193738-Cell Movement,
pubmed-meshheading:12193738-Cells, Cultured,
pubmed-meshheading:12193738-Female,
pubmed-meshheading:12193738-Fibroblasts,
pubmed-meshheading:12193738-Inflammation,
pubmed-meshheading:12193738-Interleukin-12,
pubmed-meshheading:12193738-Interleukin-12 Subunit p40,
pubmed-meshheading:12193738-Intubation, Intratracheal,
pubmed-meshheading:12193738-Lung,
pubmed-meshheading:12193738-Macrophages, Alveolar,
pubmed-meshheading:12193738-Mice,
pubmed-meshheading:12193738-Mice, Inbred C57BL,
pubmed-meshheading:12193738-Mice, Knockout,
pubmed-meshheading:12193738-Protein Subunits,
pubmed-meshheading:12193738-Pulmonary Fibrosis,
pubmed-meshheading:12193738-Recombinant Proteins,
pubmed-meshheading:12193738-Silicon Dioxide,
pubmed-meshheading:12193738-Silicosis,
pubmed-meshheading:12193738-Th1 Cells,
pubmed-meshheading:12193738-Th2 Cells
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pubmed:year |
2002
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pubmed:articleTitle |
A profibrotic function of IL-12p40 in experimental pulmonary fibrosis.
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pubmed:affiliation |
Units of Industrial Toxicology and Occupational Medicine, Faculty of Medicine, Brussels, Belgium. huaux@toxi.ucl.ac.be
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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