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Molecular Regulation of IL-6 by Asbestos

Public Domain


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  • Personal Author:
  • Description:
    Pro-inflammatory cytokines and growth factors are involved in the pathophysiological responses of asbestos-related lung diseases. Although interleukin-6 (IL-6) has been characterized as a pleiotropic cytokine with multiple biological activities, its induction and role in asbestos diseases have not been studied. Asbestos fibers were found to stimulate IL-6 secretion and mRNA transcripts in pulmonary type II-like epithelial A549 cells. IL-6 induction was dependent on the intracellular redox-oxidative state since asbestos, as well as H2O2-induced IL-6 secretion was abrogated by intracellular-acting hydroxyl scavengers and N-acetylcysteine. IL-6 induction paralleled increased DNA binding activity to the NF-kB and NF-IL-6 recognized sites in the IL-6 promoter. The NF-kB and NF-IL-6 DNA binding proteins were immunochemically characterized as a heterodimer p65/p50 and a homodimer C/EBP beta, respectively. Asbestos and H2O2-induced DNA binding activity to the NF-kB and NF-IL-6 binding sites of the IL-6 promoter were inhibited by antioxidants. The role of local IL-6 production in the pathophysiological processes of fiber-induced lung disorders was examined. Although less active than fibroblast growth factor IL-6 stimulated in vitro lung fibroblasts growth. 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-kB and NF-IL-6 transscription factors recognizing 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:
  • Keywords:
  • ISSN:
    0741-5400
  • Document Type:
    Text
  • Genre:
    Abstract or Summary
  • Place as Subject:
  • 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:
    14
  • Volume:
    62
  • NIOSHTIC Number:
    nn:20034016
  • Citation:
    J Leukoc Biol 1997 Jan; 62(Suppl):14
  • CAS Registry Number:
    Asbestos (CAS RN 1332-21-4)
  • Federal Fiscal Year:
    1997
  • Peer Reviewed:
    False
  • Source Full Name:
    Journal of Leukocyte Biology
  • Collection(s):
  • Main Document Checksum:
    urn:sha-512:92f0a7af160a46b43024b03cd7971989cf66015030569f6e3282f9f4a194e9662ec40971c26bc2439c8c2c24fe3a84b181cfb66b6b7d829012eec71de4651234
  • Download URL:
  • File Type:
    Filetype[PDF - 216.00 KB ]
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