Asbestos induces nuclear factor kappa B (NF-kappa B) DNA-binding activity and NF-kappa B-dependent gene expression in tracheal epithelial cells.
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.
Janssen
Y M
YM
Department of Pathology, University of Vermont College of Medicine.
Barchowsky
A
A
Treadwell
M
M
Driscoll
K E
KE
Mossman
B T
BT
D000818:Animals; D017638:Asbestos, Crocidolite / Q000633:toxicity*; D002478:Cells, Cultured; D006224:Cricetinae; D004247:DNA / Q000378:metabolism*; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D016758:Genes, jun; D016259:Genes, myc; D005978:Glutathione / Q000378:metabolism; D008171:Lung Diseases / Q000139:chemically induced; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014132:Trachea / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D016328:NF-kappa B; D017638:Asbestos, Crocidolite; D004247:DNA; D005978:Glutathione