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Role of transcription factor NF-KB in asbestos-induced TNF-alpha response from macrophages.
Cheng N; Shi X; Ye J; Castranova V; Chen F; Leonard SS; Vallyathan V; Rojansakul Y
Exp Mol Pathol 1999 Aug; 66(3):201-210
Asbestos exposure in humans is associated with inflammatory, fibrotic, and malignant diseases in the lung. Increasing evidence supports the hypothesis that the production of proinflammatory cytokines such as tumor necrosis factor- (TNF) is an important mediator of the pathologic responses of asbestosis. In this study, we examine the role of nuclear transcription factor-B (NF-B) and free oxygen radicals in asbestos-induced TNF gene and protein expression in lung macrophages. Exposure of the cells to crocidolite asbestos caused a parallel increase in TNF production and NF-B activation, as analyzed by enzyme-linked immunosorbent assay and electrophoretic mobility shift assay. Inhibition of NF-B by SN50, an inhibitor of NF-B nuclear translocation, or by sequence-specific oligonucleotides directed against the NF-B binding site of TNF promoter attenuated the asbestos effect on TNF production. Gene transfection assays using an expression plasmid containing a luciferase reporter gene and a TNF-derived NF-B gene promoter further indicated the dependence of NF-B activation on asbestos-induced gene expression. The effects of asbestos on NF-B and TNF activation were inhibited by oxygen radical scavengers and were enhanced by antioxidant enzyme inhibitors. These results indicate that asbestos-induced TNF gene expression is mediated through a process that involves NF-B activation and free radical reactions.
Asbestos-fibers; Asbestos-dust; Lung-disease; Lung-disorders; Lung-cancer; Lung-fibrosis; Lung-irritants; Pulmonary-system-disorders; Pulmonary-system; Respiratory-irritants; Respiratory-system-disorders
Department of Basic Pharmaceutical Sciences, West Virginia University, Health Sciences Center, P.O. Box 9530, Morgantown, WV 26506
Issue of Publication
Experimental and Molecular Pathology
Page last reviewed: September 2, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division