Please use this identifier to cite or link to this item:
|標題:||Single-Walled Carbon Nanotubes Induce Airway Hyperreactivity and Parenchymal Injury in Mice||作者:||Hsieh, W.Y.
|關鍵字:||single-walled carbon nanotubes;toxicity;matrix metallo-proteinase 12;cathepsin K;NF-kappa B;obstructive pulmonary-disease;gene-expression profiles;factor-kappa-b;lung injury;oxidative stress;pyrrolidine dithiocarbamate;macrophage;differentiation;mouse model;rat lung;inflammation||Project:||American Journal of Respiratory Cell and Molecular Biology||期刊/報告no：:||American Journal of Respiratory Cell and Molecular Biology, Volume 46, Issue 2, Page(s) 257-267.||摘要:||
Inhalation of single-walled carbon nanotubes (SWCNTs) has raised serious concerns related to potential toxic effects in the respiratory system. This study examined possible SWCNT-induced toxic mechanisms in vivo in mice. The results indicated that a single intratracheal instillation of SWCNTs could induce airway hyperreactivity and airflow obstruction and confirmed previous findings of granulomatous changes in the lung parenchyma that persisted from 7 days to 6 months after exposure. The irreversible lung pathology and functional airway alterations in the mouse model mimicked obstructive airway disease in humans. Transcriptomic analysis showed that SWCNTs might up-regulate proteinases (cathepsin K and matrix metalloproteinase [MMP] 12), chemokines C-C motif ligands (CCL2 and CCL3), and several macrophage receptors (Toll-like receptor 2, macrophage scavenger receptor 1). Pathway analyses showed that NF-kappa B-related inflammatory responses and downstream signals affecting tissue remodeling dominated the pathologic process. The NF-kappa B inhibitor pyrrolidine dithiocarbamate attenuated SWCNT-induced airway hyperreactivity, chronic airway inflammation, and MMP12 and cathepsin K expression when administered in vivo, whereas a cathepsin K inhibitor could partially reduce airway hyperreactivity and granulomatous changes in the SWCNT-treated group. The up-regulation of cathepsin K and MMP12 by SWCNTs was further confirmed via in vitro coculture of bronchoalveolar macrophages with lung epithelial/mesenchymal cells but not in macrophages without coculture, indicating that SWCNT-induced MMP12 and cathespin K were cell-type specific and cell-cell interaction dependent. In conclusion, exposure to SWCNTs may cause irreversible obstructive airway disease. Nanotoxicogenomics uncovered novel mechanisms underlying SWCNT-induced lung diseases, implicating MMP12 and cathepsin K in the pathologic injury as potential biomarkers or therapeutic targets.
|Appears in Collections:||期刊論文|
Show full item record
TAIR Related Article
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.