| Single-Walled Carbon Nanotubes Induce Airway Hyper-Reactivity and Parenchymal Injury in Mice. | |
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MedLine Citation:
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PMID: 21960547 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Inhalation of single-walled carbon nanotubes (SWCNTs) has raised serious concerns related to potential toxic effects in the respiratory system. This study examined possible SWCNTs-induced toxic mechanisms in vivo in mice. The results indicated that a single intra-tracheal instillation of SWCNTs could induce airway hyper-reactivity 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 MMP12), chemokines (CCL2 and CCL3), and several macrophage receptors (Toll-like receptor 2, MSR1). Pathway analyses showed that NF-B related inflammatory responses and downstream signals affecting tissue remodeling dominated the pathologic process. The NF-B inhibitor, PDTC, attenuated SWCNTs-induced airway hyper-reactivity, chronic airway inflammation, and MMP12 and Cathepsin K expression when administered in vivo, whereas a Cathepsin K inhibitor could partially reduce airway hyper-reactivity and granulomatous changes in the SWCNTs-treated group. The up-regulation of cathepsin K and MMP12 by SWCNTs was further confirmed via in vitro co-culture of BAL macrophages with lung epithelial/mesenchymal cells, but not in macrophages without co-culture, indicating that SWCNTs-induced MMP12 and cathespin K were both cell-type specific and cell-cell interaction dependent. In conclusion, exposure to SWCNTs may cause irreversible obstructive airway disease. Nanotoxicogenomics uncovered novel mechanisms underlying SWCNTs-induced lung diseases, implicating MMP12 and cathepsin K in the pathologic injury as potential biomarkers or therapeutic targets. |
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Authors:
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Wan-Yu Hsieh; Cheng-Chung Chou; Chao-Chi Ho; Sung-Liang Yu; Hsuan-Yu Chen; Han-Yi E Chou; Jeremy Jw Chen; Huei-Wen Chen; Pan-Chyr Yang |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-9-29 |
Journal Detail:
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Title: American journal of respiratory cell and molecular biology Volume: - ISSN: 1535-4989 ISO Abbreviation: - Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-9-30 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8917225 Medline TA: Am J Respir Cell Mol Biol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Province of China; Graduate Institute of Toxicology, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan, Province of China. |
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