Asbestos induces nuclear factor kappa B (NF-kappa B) DNA-binding activity and NF-kappa B-dependent gene expression in tracheal epithelial cells
| Autor: | Melinda D. Treadwell, Aaron Barchowsky, Kevin E. Driscoll, Brooke T. Mossman, Yvonne M. W. Janssen |
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| Rok vydání: | 1995 |
| Předmět: |
Lung Diseases
Cell Genes myc Biology Epithelium chemistry.chemical_compound Genes jun Cricetinae Gene expression medicine Animals Northern blot Promoter Regions Genetic Gene Transcription factor Cells Cultured Regulation of gene expression Multidisciplinary Asbestos Crocidolite NF-kappa B Epithelial Cells DNA NFKB1 Glutathione Molecular biology Trachea medicine.anatomical_structure Gene Expression Regulation chemistry Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences. 92:8458-8462 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.92.18.8458 |
| Popis: | Nuclear factor kappa B (NF-kappa B) is a transcription factor regulating expression of genes intrinsic to inflammation and cell proliferation--features of asbestos-associated diseases. In studies here, crocidolite asbestos caused protracted and dose-responsive increases in proteins binding to nuclear NF-kappa B-binding DNA elements in hamster tracheal epithelial (HTE) cells. This binding was modulated by cellular glutathione levels. Antibodies recognizing p65 and p50 protein members of the NF-kappa B family revealed these proteins in two of the DNA complexes. Transient transfection assays with a construct containing six NF-kappa B-binding DNA consensus sites linked to a luciferase reporter gene indicated that asbestos induced transcriptional activation of NF-kappa B-dependent genes, an observation that was confirmed by northern blot analyses for c-myc mRNA levels in HTE cells. Studies suggest that NF-kappa B induction by asbestos is a key event in regulation of multiple genes involved in the pathogenesis of asbestos-related lung cancers. |
| Databáze: | OpenAIRE |
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