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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2004-2-5
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pubmed:abstractText |
Chorioamnionitis is associated with increased risks of perinatal respiratory failure; however, components of the inflammatory acute-phase response are known to actively promote lung maturation. To manipulate this relationship, we examined the effect of the thymic immunomodulator thymulin on fetal lung mesenchyme-epithelial differentiation during exposure to Escherichia coli lipopolysaccharide (LPS). Gestation day 14 fetal rat lung explants were cultured for 96 h at fetal (23 mmHg) or ambient (142 mmHg) Po(2). Airway surface complexity (ASC, perimeter/ radical area(2)) was greater at fetal vs. ambient Po(2); however, exposure to 0.1-50 microg/ml LPS significantly raised ASC at 2 microg/ml in ambient Po(2) explants. LPS (50 microg/ml) depressed ASC in both conditions to untreated ambient Po(2) control values without changes in necrosis or apoptosis. To manipulate LPS-evoked TNF-alpha and IL-6 release, we exposed explants and A549 cells to combinations of 50 microg/ml LPS, 10 microM ZnCl(2), and 0.1-1,000 ng/ml thymulin at either Po(2). Thymulin+Zn(2+) suppressed and potentiated LPS-evoked TNF-alpha and IL-6 release, yielding an IC(50(TNF-alpha)) of 0.5 +/- 0.01 ng/ml and EC(50(IL-6)) of 1.4 +/- 0.3 ng/ml in A549 cells. This was accompanied by activation of the p38 MAPKMAPKAP-K2 pathway with sustained expression of TNF-alpha and IL-6 transcripts at ambient Po(2). LPS+thymulin+Zn(2+)-treated explants showed proliferation of CCAAT-enhancer binding protein-beta (C/EBPbeta) and fibroblast growth factor-9 immunoreactive mesenchyme, which was abolished by IL-6 antisense oligonucleotides. The posttranscriptional suppression of immunogenic TNF-alpha synthesis coupled with raised IL-6 and C/EBPbeta-dependent mesenchyme proliferation suggests a role for bioactive thymulin in regulating regenerative repair in the fetal lung.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adjuvants, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Enhancer-Binding Protein-beta,
http://linkedlifedata.com/resource/pubmed/chemical/FGF9 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Fibroblast Growth Factor 10,
http://linkedlifedata.com/resource/pubmed/chemical/Fibroblast Growth Factor 9,
http://linkedlifedata.com/resource/pubmed/chemical/Fibroblast Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/MAP-kinase-activated kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Oxygen,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Thymic Factor, Circulating,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Zinc
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1040-0605
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
286
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
L473-87
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:12639846-Adenocarcinoma,
pubmed-meshheading:12639846-Adjuvants, Immunologic,
pubmed-meshheading:12639846-CCAAT-Enhancer-Binding Protein-beta,
pubmed-meshheading:12639846-Cell Differentiation,
pubmed-meshheading:12639846-Cell Division,
pubmed-meshheading:12639846-Cell Line, Tumor,
pubmed-meshheading:12639846-Fetus,
pubmed-meshheading:12639846-Fibroblast Growth Factor 10,
pubmed-meshheading:12639846-Fibroblast Growth Factor 9,
pubmed-meshheading:12639846-Fibroblast Growth Factors,
pubmed-meshheading:12639846-Humans,
pubmed-meshheading:12639846-Hyperplasia,
pubmed-meshheading:12639846-Interleukin-6,
pubmed-meshheading:12639846-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:12639846-Lipopolysaccharides,
pubmed-meshheading:12639846-Lung,
pubmed-meshheading:12639846-Mesoderm,
pubmed-meshheading:12639846-Oxygen,
pubmed-meshheading:12639846-Protein-Serine-Threonine Kinases,
pubmed-meshheading:12639846-Signal Transduction,
pubmed-meshheading:12639846-Thymic Factor, Circulating,
pubmed-meshheading:12639846-Transcription, Genetic,
pubmed-meshheading:12639846-Tumor Necrosis Factor-alpha,
pubmed-meshheading:12639846-Zinc
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pubmed:year |
2004
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pubmed:articleTitle |
Thymulin evokes IL-6-C/EBPbeta regenerative repair and TNF-alpha silencing during endotoxin exposure in fetal lung explants.
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pubmed:affiliation |
Tayside Inst. of Child Health, Maternal and Child Health Sciences, Ninewells Hospital and Medical School, Univ. of Dundee, Dundee, DD1 9SY, UK. s.c.land@dundee.ac.uk
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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