Role of Transcription Factor NF-KB in Asbestos-Induced TNF-Alpha Response from Macrophages

Details

• Personal Author:
  Castranova, Vincent ; Chen F ; Cheng N ; Leonard, Stephen S. ; Rojansakul Y ; Shi X ; Vallyathan V ; Ye J
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Asbestos Dust Inorganic Chemicals Irritants Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Asbestos-dust Asbestos-fibers Lung-cancer Lung-disease Lung-disorders Lung-fibrosis Lung-irritants Pulmonary-system Pulmonary-system-disorders Respiratory-irritants Respiratory-system-disorders

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• ISSN:
  0014-4800
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; Pennsylvania ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  201-210
• Volume:
  66
• Issue:
  3
• NIOSHTIC Number:
  nn:20027448
• Citation:
  Exp Mol Pathol 1999 Aug; 66(3):201-210
• Contact Point Address:
  Department of Basic Pharmaceutical Sciences, West Virginia University, Health Sciences Center, P.O. Box 9530, Morgantown, WV 26506
• Email:
  yrojanasakul@hsc.wvu.edu
• CAS Registry Number:
  Asbestos (CAS RN 1332-21-4)
• Federal Fiscal Year:
  1999
• Peer Reviewed:
  True
• Source Full Name:
  Experimental and Molecular Pathology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:10e045e46140d0061c6703cb653a108c0c1125dc8c218a7e21ee355fa22b53b8172507585d971f656383abf7a440cdd4987a0bd95ee5037f9bafa111774f7165
• Download URL:
  https://stacks.cdc.gov/view/cdc/197581/cdc_197581_DS1.pdf
• File Type:
  [PDF - 183.80 KB ]