Molecular Regulation of IL-6 Activation by Asbestos in Lung Epithelial Cells: Role of Reactive Oxygen Species

Details

• Personal Author:
  Erkan M ; Kommineni C ; Luster MI ; Munson AE ; Rom, William N. ; Simeonova PP ; Toriumi W
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Asbestos Cytology DNA Fibrosis Inorganic Chemicals Lung Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Asbestos-products Asbestosis Deoxyribonucleic-acids Lung-disease Lung-disorders Lung-fibrosis Lung-irritants Lung-tissue
• ISSN:
  0022-1767
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  159
• Issue:
  8
• NIOSHTIC Number:
  nn:20025227
• Citation:
  J Immunol 1997 Oct; 159(8):3921-3928
• Contact Point Address:
  Dr. Petia P Simeonova, Health Effects Laboratory Division, National Insitute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505
• CAS Registry Number:
  Asbestos (CAS RN 1332-21-4)
• Federal Fiscal Year:
  1998
• Peer Reviewed:
  True
• Source Full Name:
  The Journal of Immunology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:35899f1300a313e0467052679d745f22b82aac640669b6d67834b4bc4f4cd92440e8992704ff47aefd2f0c516b6c82dcdffcec75ae10630e7db6cffb1f0be244
• Download URL:
  https://stacks.cdc.gov/view/cdc/196693/cdc_196693_DS1.pdf
• File Type:
  [PDF - 4.02 MB ]