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Systematic analysis of multi-walled carbon nanotube-induced cellular signaling and gene expression in human small airway epithelial cells.

Authors
Snyder-Talkington-BN; Pacurari-M; Dong-C; Leonard-SS; Schwegler-Berry-D; Castranova-V; Qian-Y; Guo-NL
Source
Toxicol Sci 2013 May; 133(1):79-89
NIOSHTIC No.
20042182
Abstract
Multi-walled carbon nanotubes (MWCNT) are one of the most commonly produced nanomaterials, and pulmonary exposure during production, use, and disposal is a concern for the developing nanotechnology field. The airway epithelium is the first line of defense against inhaled particles. In a mouse model, MWCNT were reported to reach the alveolar space of the lung after in vivo exposure, penetrate the epithelial lining, and result in inflammation and progressive fibrosis. This study sought to determine the cellular and gene expression changes in small airway epithelial cells (SAEC) after in vitro exposure to MWCNT in an effort to elucidate potential toxicity mechanisms and signaling pathways. A direct interaction between SAEC and MWCNT was confirmed by both internalization of MWCNT as well as an interaction at the cell periphery. Following exposure, SAEC showed time-dependent increases in reactive oxygen species production, total protein phospho-tyrosine and phospho-threonine levels, and migratory behavior. Analysis of gene and protein expression suggested altered regulation of multiple biomarkers of lung damage, carcinogenesis, and tumor progression, as well as genes involved in related signaling pathways. These results demonstrate that MWCNT exposure resulted in the activation of SAEC. Gene expression data derived from MWCNT exposure provides information that may be used to elucidate the underlying mode of action of MWCNT in the small airway and suggest potential prognostic gene signatures for risk assessment.
Keywords
Nanotechnology; Pulmonary-system; Pulmonary-system-disorders; Pulmonary-function; Respiration; Respiratory-irritants; Respiratory-system-disorders; Inhalants; Animals; Laboratory-animals; Exposure-levels; Risk-factors; Lung; Fibrosis; Cellular-reactions; Biomarkers; Carcinogenesis; Tumors; Genes; Author Keywords: Multi-walled carbon nanotubes; airway epithelial damage; signaling pathways; molecular mechanisms
Contact
Brandi N. Snyder-Talkington, Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505
CODEN
TOSCF2
Publication Date
20130501
Document Type
Journal Article
Fiscal Year
2013
NTIS Accession No.
NTIS Price
Identifying No.
B20130221
Issue of Publication
1
ISSN
1096-6080
NIOSH Division
HELD
Priority Area
Manufacturing
Source Name
Toxicological Sciences
State
WV
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