Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/67868
DC FieldValueLanguage
dc.contributor.authorHsieh, W.Y.en_US
dc.contributor.authorChou, C.C.en_US
dc.contributor.authorHo, C.C.en_US
dc.contributor.authorYu, S.L.en_US
dc.contributor.authorChen, H.Y.en_US
dc.contributor.authorChou, H.Y.E.en_US
dc.contributor.authorChen, J.J.W.en_US
dc.contributor.authorChen, H.W.en_US
dc.contributor.authorYang, P.C.en_US
dc.date2012zh_TW
dc.date.accessioned2014-06-11T05:55:51Z-
dc.date.available2014-06-11T05:55:51Z-
dc.identifier.issn1044-1549zh_TW
dc.identifier.urihttp://hdl.handle.net/11455/67868-
dc.description.abstractInhalation 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.en_US
dc.language.isoen_USzh_TW
dc.relationAmerican Journal of Respiratory Cell and Molecular Biologyen_US
dc.relation.ispartofseriesAmerican Journal of Respiratory Cell and Molecular Biology, Volume 46, Issue 2, Page(s) 257-267.en_US
dc.relation.urihttp://dx.doi.org/10.1165/rcmb.2011-0010OCen_US
dc.subjectsingle-walled carbon nanotubesen_US
dc.subjecttoxicityen_US
dc.subjectmatrix metallo-proteinase 12en_US
dc.subjectcathepsin Ken_US
dc.subjectNF-kappa Ben_US
dc.subjectobstructive pulmonary-diseaseen_US
dc.subjectgene-expression profilesen_US
dc.subjectfactor-kappa-ben_US
dc.subjectlung injuryen_US
dc.subjectoxidative stressen_US
dc.subjectpyrrolidine dithiocarbamateen_US
dc.subjectmacrophageen_US
dc.subjectdifferentiationen_US
dc.subjectmouse modelen_US
dc.subjectrat lungen_US
dc.subjectinflammationen_US
dc.titleSingle-Walled Carbon Nanotubes Induce Airway Hyperreactivity and Parenchymal Injury in Miceen_US
dc.typeJournal Articlezh_TW
dc.identifier.doi10.1165/rcmb.2011-0010OCzh_TW
item.cerifentitytypePublications-
item.grantfulltextnone-
item.languageiso639-1en_US-
item.fulltextno fulltext-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.openairetypeJournal Article-
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