https://scholars.lib.ntu.edu.tw/handle/123456789/502888
標題: | Single-walled carbon nanotubes induce airway hyperreactivity and parenchymal injury in mice | 作者: | Hsieh W.-Y. Chou C.-C. CHAO-CHI HO SUNG-LIANG YU Chen H.-Y. HAN-YI E. CHOU Chen J.J.W. HUEI-WEN CHEN PAN-CHYR YANG |
公開日期: | 2012 | 卷: | 46 | 期: | 2 | 起(迄)頁: | 257-267 | 來源出版物: | American Journal of Respiratory Cell and Molecular Biology | 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-κB-related inflammatory responses and downstream signals affecting tissue remodeling dominated the pathologic process. The NF-κB 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. Copyright ? 2012 by the American Thoracic Society. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/502888 | ISSN: | 1044-1549 | DOI: | 10.1165/rcmb.2011-0010OC | SDG/關鍵字: | cathepsin K; cathepsin K inhibitor; cutaneous T cell attracting chemokine; macrophage elastase; macrophage inflammatory protein 1alpha; pentoxifylline; pyrrolidine dithiocarbamate; single walled nanotube; toll like receptor 2; airway hyperreactivity; airway inflammation; airway obstruction; animal experiment; animal model; article; cell interaction; controlled study; gene expression; in vivo study; inflammation; lung disease; lung injury; macrophage; male; mesenchyme cell; mouse; nonhuman; obstructive airway disease; upregulation; Animals; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Coculture Techniques; Gene Expression Profiling; Lung; Male; Mice; Mice, Inbred ICR; Nanotubes, Carbon; Transcriptome; Up-Regulation; Mus |
顯示於: | 醫學檢驗暨生物技術學系 |
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