Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2002-8-23
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
169
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2653-61
pubmed:dateRevised
2007-11-14
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
pubmed:year
2002
pubmed:articleTitle
A profibrotic function of IL-12p40 in experimental pulmonary fibrosis.
pubmed:affiliation
Units of Industrial Toxicology and Occupational Medicine, Faculty of Medicine, Brussels, Belgium. huaux@toxi.ucl.ac.be
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't