Essential Role of ROS-Mediated NFAT Activation in TNF-Alpha Induction by Crystalline Silica Exposure

Details

• Personal Author:
  Costa M ; Ding J ; Ding M ; Huang C ; Ke QD ; Li JX ; Liu BC ; Wang LY
• Description:
  Occupational exposure to crystalline silica has been associated with progressive pulmonary silicosis and lung cancer, but the underlying molecular mechanisms are not well understood. Previous studies have shown that crystalline silica exposure can generate reactive oxygen species (ROS) and induce the expression of the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) in cells. TNF-alpha is believed to be critical in the development of silica-related diseases. Thus it will be of significance to understand the mechanisms of TNF-alpha induction by silica exposure. Given the fact that the transcription factor nuclear factor of activated T cells (NFAT) plays an important role in the regulation of TNF-alpha and can also be activated by ROS, in this study we investigated the potential role of ROS in silica-induced NFAT activity as well as TNF-alpha expression in Cl41 cells. The results showed that exposure of cells to silica led to NFAT transactivation and TNF-alpha induction, where superoxide anion radical (O(2)(-).), but not H(2)O(2), was involved. The knockdown of NFAT3 by its specific small interfering RNA significantly attenuated the silica-induced TNF-alpha transcription. This study demonstrated that silica was able to activate NFAT in an O(2)(-).-dependent manner, which was required for TNF-alpha induction. [Description provided by NIOSH]
• Subjects:
  Aluminum Silicates Dust Lung Lung Diseases Neoplasms Occupational Diseases Occupational Exposure Occupational Health Quartz Respiratory System Respiratory Tract Diseases Safety Silicon Dioxide

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• Keywords:
  Cancer Diseases Lung-cancer Occupational-diseases Occupational-exposure Pulmonary-system-disorders Quartz-dust Silica-dusts Silicates Silicosis
• ISSN:
  1040-0605
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  New York ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  291
• Issue:
  2
• NIOSHTIC Number:
  nn:20030662
• Citation:
  Am J Physiol Lung Cell Mol Physiol 2006 Aug; 291(2):L257-L264
• Contact Point Address:
  C. Huang, Nelson Institute of Environmental Medicine, New York Univ. School of Medicine, 57 Old Forge Rd., Tuxedo, NY 10987
• Email:
  chuanshu@env.med.nyu.edu
• CAS Registry Number:
  Quartz (SiO2) (CAS RN 14808-60-7)
• Federal Fiscal Year:
  2006
• NORA Priority Area:
  Research Tools and Approaches: Cancer Research Methods
• Peer Reviewed:
  True
• Source Full Name:
  American Journal of Physiology: Lung Cellular and Molecular Physiology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:3b3bc751f47f2aed744cd07a83c8fac6281cd48d19bd7427b7ecde8802072f7c5d460abd8d94a04e0ebd6ec1977c94f3303f084c91916ce3861e13d9ed3a065a
• Download URL:
  https://stacks.cdc.gov/view/cdc/191202/cdc_191202_DS1.pdf
• File Type:
  [PDF - 290.34 KB ]