AJP - Lung Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Lung Cell Mol Physiol 291: L257-L264, 2006. First published February 17, 2006; doi:10.1152/ajplung.00007.2006
1040-0605/06 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
291/2/L257    most recent
00007.2006v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via ISI Web of Science (1)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ke, Q.
Right arrow Articles by Huang, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ke, Q.
Right arrow Articles by Huang, C.

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

Qingdong Ke,1 Jingxia Li,1 Jin Ding,1 Min Ding,2 Liying Wang,2 Bingci Liu,3 Max Costa,1 and Chuanshu Huang1

1Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, New York; 2Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia; and 3National Institute of Occupational Health and Poisons Control, Chinese Center for Diseases Control and Prevention, Beijing, China

Submitted 4 January 2006 ; accepted in final form 15 February 2006

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 (O2–·), but not H2O2, 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 O2–·-dependent manner, which was required for TNF-{alpha} induction.

silica; nuclear factor of activated T cells; tumor necrosis factor-{alpha}; reactive oxygen species; signal transduction


Address for reprint requests and other correspondence: C. Huang, Nelson Institute of Environmental Medicine, New York Univ. School of Medicine, 57 Old Forge Rd., Tuxedo, NY 10987 (e-mail: chuanshu{at}env.med.nyu.edu)






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2006 by the American Physiological Society.