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Signaling pathways controlling the production of inflammatory mediators in response to crystalline silica exposure: role of reactive oxygen/nitrogen species.

Authors
Castranova-V
Source
Free Radic Biol Med 2004 Oct; 37(7):916-925
NIOSHTIC No.
20025453
Abstract
Occupational exposure to crystalline silica has been linked to pulmonary fibrosis and lung cancer. Surface properties of crystalline silica are critical to the production of oxidant species, chemokines, inflammatory cytokines, and proliferative factors involved in the initiation and progression of silica-induced damage, inflammation, alveolar type II cell hyperplasia, fibroblast activation, and disease. The transcription factors nuclear factor kappaB (NF-kappaB) and activator protein 1 (AP-1) have been shown to play key roles in gene promotion for inflammatory mediators, oncogenes, and growth factors. This review summarizes evidence that in vitro and in vivo exposure to crystalline silica results in activation of NF-kappaB and AP-1. Signaling pathways for activation of these transcription factors are described. In addition, the role of silica-induced reactive oxygen species and nitric oxide in the activation of these signaling events is presented. Last, the generalizability of mechanisms regulating silica-induced pulmonary responses to pulmonary reactions to other occupational particles is discussed.
Keywords
Silica-dusts; Silicates; Exposure-levels; Exposure-assessment; Occupational-exposure; Pulmonary-system-disorders; Fibrosis; Lung-cancer; Respiratory-system-disorders; In-vivo-studies; In-vitro-studies; Free-radicals
Contact
Vincent Castranova, Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, MS L-2015, 1095 Willowdale Road, Morgantown, WV 26505, USA
CODEN
FRBMEH
CAS No.
14808-60-7
Publication Date
20041001
Document Type
Journal Article
Fiscal Year
2005
NTIS Accession No.
NTIS Price
Issue of Publication
7
ISSN
0891-5849
NIOSH Division
HELD
Source Name
Free Radical Biology and Medicine
State
WV
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