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Essential role of ROS-mediated NFAT activation in TNF-alpha induction by crystalline silica exposure.

Authors
Ke-QD; Li-JX; Ding-J; Ding-M; Wang-LY; Liu-BC; Costa-M; Huang-C
Source
Am J Physiol, Lung Cell Mol Physiol 2006 Aug; 291(2):L257-L264
NIOSHTIC No.
20030662
Abstract
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.
Keywords
Silicates; Silica-dusts; Quartz-dust; Occupational-exposure; Silicosis; Lung-cancer; Cancer; Pulmonary-system-disorders; Occupational-diseases; Diseases
Contact
C. Huang, Nelson Institute of Environmental Medicine, New York Univ. School of Medicine, 57 Old Forge Rd., Tuxedo, NY 10987
CODEN
APLPE7
CAS No.
14808-60-7
Publication Date
20060801
Document Type
Journal Article
Email Address
chuanshu@env.med.nyu.edu
Fiscal Year
2006
NTIS Accession No.
NTIS Price
Issue of Publication
2
ISSN
1040-0605
NIOSH Division
HELD
Priority Area
Research Tools and Approaches: Cancer Research Methods
Source Name
American Journal of Physiology: Lung Cellular and Molecular Physiology
State
NY
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