| Radical-containing ultrafine particulate matter initiates epithelial-to-mesenchymal transitions in airway epithelial cells. | |
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MedLine Citation:
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PMID: 23087054 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Environmentally persistent free radicals (EPFRs) in combustion-generated particulate matter (PM) are capable of inducing pulmonary pathologies and contributing to the development of environmental asthma. In vivo exposure of infant rats to EPFRs demonstrates their ability to induce airway hyperresponsiveness to methacholine, a hallmark of asthma. However, the mechanisms by which combustion-derived EPFRs elicit in vivo responses remain elusive. In this study, we used a chemically defined EPFR consisting of approximately 0.2 μm amorphrous silica containing 3% cupric oxide with the organic pollutant 1,2-dichlorobenzene (DCB-230). DCB-230 possesses similar radical content to urban-collected EPFRs but offers several advantages, including lack of contaminants and chemical uniformity. DCB-230 was readily taken up by BEAS-2B and at high doses (200 μg/cm(2)) caused substantial necrosis. At low doses (20 μg/cm(2)), DCB-230 particles caused lysosomal membrane permeabilization, oxidative stress, and lipid peroxidation within 24 hours of exposure. During this period, BEAS-2B underwent epithelial-to-mesenchymal transition (EMT), including loss of epithelial cell morphology, decreased E-cadherin expression, and increased α-smooth muscle actin (α-SMA) and collagen I production. Similar results were observed in neonatal air-liquid interface culture (i.e., disruption of epithelial integrity and EMT). Acute exposure of infant mice to DCB-230 resulted in EMT, as confirmed by lineage tracing studies and evidenced by coexpression of epithelial E-cadherin and mesenchymal α-SMA proteins in airway cells and increased SNAI1 expression in the lungs. EMT in neonatal mouse lungs after EPFR exposure may provide an explanation for epidemiological evidence supporting PM exposure and increased risk of asthma. |
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Authors:
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Paul T Thevenot; Jordy Saravia; Nili Jin; Joseph D Giaimo; Regina E Chustz; Sarah Mahne; Matthew A Kelley; Valeria Y Hebert; Barry Dellinger; Tammy R Dugas; Francesco J Demayo; Stephania A Cormier |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-10-18 |
Journal Detail:
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Title: American journal of respiratory cell and molecular biology Volume: 48 ISSN: 1535-4989 ISO Abbreviation: Am. J. Respir. Cell Mol. Biol. Publication Date: 2013 Feb |
Date Detail:
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Created Date: 2013-02-04 Completed Date: 2013-03-21 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 8917225 Medline TA: Am J Respir Cell Mol Biol Country: United States |
Other Details:
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Languages: eng Pagination: 188-97 Citation Subset: IM |
Affiliation:
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Louisiana State University Health Sciences Center, Department of Pharmacology & Experimental Therapeutics, New Orleans, LA 70112, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Air Pollutants
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toxicity* Animals Animals, Newborn Bronchioles / cytology, drug effects Cell Line Cell Membrane Permeability Dose-Response Relationship, Drug Epithelial Cells / drug effects Epithelial-Mesenchymal Transition / drug effects* Mice Oxidative Stress Particle Size |
| Grant Support | |
ID/Acronym/Agency:
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AA007577/AA/NIAAA NIH HHS; P42 ES013648/ES/NIEHS NIH HHS; P42ES013648/ES/NIEHS NIH HHS; R01 ES015050/ES/NIEHS NIH HHS; R01ES015050/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Air Pollutants |
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