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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
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pubmed:dateCreated |
1997-11-7
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pubmed:abstractText |
IL-6 has been characterized as a pleiotropic cytokine with multiple biologic activities, but its induction and role in asbestos diseases have not been studied. Asbestos fibers were found to stimulate IL-6 expression and secretion in pulmonary type II-like epithelial A549 cells as well as in normal human bronchial epithelial cells. IL-6 induction was dependent on the intracellular redox-oxidative state, since intracellular hydroxyl scavengers and N-acetylcysteine, a precursor of glutathione, abrogated IL-6 secretion by asbestos or H2O2. IL-6 induction paralleled increased DNA binding activity to the nuclear factor-kappa B (NF-kappa B)- and NF-IL-6-recognized sites in the IL-6 promoter. The NF-kappa B and NF-IL-6 DNA binding proteins were immunochemically characterized as a heterodimer p65/p50 and a homodimer C/EBP beta, respectively. Stimulation of DNA binding activity to the NF-kappa B and NF-IL-6 binding sites of the IL-6 promoter by asbestos or H2O2 were inhibited by tetramethylthiourea, a hydroxyl radical scavenger. The role of local IL-6 production in the pathophysiologic processes of fiber-induced lung disorders was examined. Although less active than fibroblast growth factor, human rIL-6 also stimulated lung fibroblast growth, as evidenced by increased [3H]thymidine incorporation. Furthermore, elevated IL-6 levels were found in bronchoalveolar lavage fluids from patients diagnosed with lung fibrosis and work-related histories of long term asbestos exposure. Taken together, the results suggest that asbestos-induced oxidative stress is involved in the activation of NF-kappa B and NF-IL-6 transcription factors, which recognize the IL-6 promoter. The resulting increase in IL-6 expression may be involved in both inflammatory and fibrotic processes in the lung.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
159
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3921-8
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pubmed:dateRevised |
2004-11-17
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pubmed:meshHeading |
pubmed-meshheading:9378980-Adenocarcinoma, Bronchiolo-Alveolar,
pubmed-meshheading:9378980-Asbestos, Crocidolite,
pubmed-meshheading:9378980-Bronchoalveolar Lavage Fluid,
pubmed-meshheading:9378980-Cells, Cultured,
pubmed-meshheading:9378980-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:9378980-Epithelial Cells,
pubmed-meshheading:9378980-Gene Expression Regulation,
pubmed-meshheading:9378980-Humans,
pubmed-meshheading:9378980-Interleukin-6,
pubmed-meshheading:9378980-Lung,
pubmed-meshheading:9378980-Lung Neoplasms,
pubmed-meshheading:9378980-Nuclear Proteins,
pubmed-meshheading:9378980-Oxidation-Reduction,
pubmed-meshheading:9378980-Protein Binding,
pubmed-meshheading:9378980-Reactive Oxygen Species,
pubmed-meshheading:9378980-Tumor Cells, Cultured
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pubmed:year |
1997
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pubmed:articleTitle |
Molecular regulation of IL-6 activation by asbestos in lung epithelial cells: role of reactive oxygen species.
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pubmed:affiliation |
Toxicology and Molecular Biology Branch, National Institute of Occupational Safety and Health, Morgantown, WV 26505, USA.
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pubmed:publicationType |
Journal Article
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