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Murine Lung Responses to Ambient Particulate Matter: Genomic Analysis and Influence on Airway Hyperresponsiveness

BACKGROUND: Asthma is a complex disease characterized by airway hyperresponsiveness (AHR) and chronic airway inflammation. Epidemiologic studies have demonstrated that exposures to environmental factors such as ambient particulate matter (PM), a major air pollutant, contribute to increased asthma pr...

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Autores principales: Wang, Ting, Moreno-Vinasco, Liliana, Huang, Yong, Lang, Gabriel D., Linares, Jered D., Goonewardena, Sascha N., Grabavoy, Alayna, Samet, Jonathan M., Geyh, Alison S., Breysse, Patrick N., Lussier, Yves A., Natarajan, Viswanathan, Garcia, Joe G.N.
Formato: Texto
Lenguaje:English
Publicado: National Institute of Environmental Health Sciences 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2592270/
https://www.ncbi.nlm.nih.gov/pubmed/19057703
http://dx.doi.org/10.1289/ehp.11229
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author Wang, Ting
Moreno-Vinasco, Liliana
Huang, Yong
Lang, Gabriel D.
Linares, Jered D.
Goonewardena, Sascha N.
Grabavoy, Alayna
Samet, Jonathan M.
Geyh, Alison S.
Breysse, Patrick N.
Lussier, Yves A.
Natarajan, Viswanathan
Garcia, Joe G.N.
author_facet Wang, Ting
Moreno-Vinasco, Liliana
Huang, Yong
Lang, Gabriel D.
Linares, Jered D.
Goonewardena, Sascha N.
Grabavoy, Alayna
Samet, Jonathan M.
Geyh, Alison S.
Breysse, Patrick N.
Lussier, Yves A.
Natarajan, Viswanathan
Garcia, Joe G.N.
author_sort Wang, Ting
collection PubMed
description BACKGROUND: Asthma is a complex disease characterized by airway hyperresponsiveness (AHR) and chronic airway inflammation. Epidemiologic studies have demonstrated that exposures to environmental factors such as ambient particulate matter (PM), a major air pollutant, contribute to increased asthma prevalence and exacerbations. OBJECTIVE: We investigated pathophysiologic responses to Baltimore, Maryland, ambient PM (median diameter, 1.78 μm) in a murine model of asthma and attempted to identify PM-specific genomic/molecular signatures. METHODS: We exposed ovalbumin (OVA)-sensitized A/J mice intratracheally to PM (20 mg/kg), and assayed both AHR and bronchoalveolar lavage (BAL) on days 1, 4, and 7 after PM exposure. Lung gene expression profiling was analyzed in OVA- and PM-challenged mice. RESULTS: Consistent with this murine model of asthma, we observed significant increases in airway responsiveness in OVA-treated mice, with PM exposure inducing significant changes in AHR in both naive mice and OVA-induced asthmatic mice. PM evoked eosinophil and neutrophil infiltration into airways, elevated BAL protein content, and stimulated secretion of type 1 T helper (T(H)1) cytokines [interferon-γ, interleukin-6 (IL-6), tumor necrosis factor-α] and T(H)2 cytokines (IL-4, IL-5, eotaxin) into murine airways. Furthermore, PM consistently induced expression of genes involved in innate immune responses, chemotaxis, and complement system pathways. CONCLUSION: This study is consistent with emerging epidemiologic evidence and indicates that PM exposure evokes proinflammatory and allergic molecular signatures that may directly contribute to the asthma susceptibility in naive subjects and increased severity in affected asthmatics.
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spelling pubmed-25922702008-12-04 Murine Lung Responses to Ambient Particulate Matter: Genomic Analysis and Influence on Airway Hyperresponsiveness Wang, Ting Moreno-Vinasco, Liliana Huang, Yong Lang, Gabriel D. Linares, Jered D. Goonewardena, Sascha N. Grabavoy, Alayna Samet, Jonathan M. Geyh, Alison S. Breysse, Patrick N. Lussier, Yves A. Natarajan, Viswanathan Garcia, Joe G.N. Environ Health Perspect Research BACKGROUND: Asthma is a complex disease characterized by airway hyperresponsiveness (AHR) and chronic airway inflammation. Epidemiologic studies have demonstrated that exposures to environmental factors such as ambient particulate matter (PM), a major air pollutant, contribute to increased asthma prevalence and exacerbations. OBJECTIVE: We investigated pathophysiologic responses to Baltimore, Maryland, ambient PM (median diameter, 1.78 μm) in a murine model of asthma and attempted to identify PM-specific genomic/molecular signatures. METHODS: We exposed ovalbumin (OVA)-sensitized A/J mice intratracheally to PM (20 mg/kg), and assayed both AHR and bronchoalveolar lavage (BAL) on days 1, 4, and 7 after PM exposure. Lung gene expression profiling was analyzed in OVA- and PM-challenged mice. RESULTS: Consistent with this murine model of asthma, we observed significant increases in airway responsiveness in OVA-treated mice, with PM exposure inducing significant changes in AHR in both naive mice and OVA-induced asthmatic mice. PM evoked eosinophil and neutrophil infiltration into airways, elevated BAL protein content, and stimulated secretion of type 1 T helper (T(H)1) cytokines [interferon-γ, interleukin-6 (IL-6), tumor necrosis factor-α] and T(H)2 cytokines (IL-4, IL-5, eotaxin) into murine airways. Furthermore, PM consistently induced expression of genes involved in innate immune responses, chemotaxis, and complement system pathways. CONCLUSION: This study is consistent with emerging epidemiologic evidence and indicates that PM exposure evokes proinflammatory and allergic molecular signatures that may directly contribute to the asthma susceptibility in naive subjects and increased severity in affected asthmatics. National Institute of Environmental Health Sciences 2008-11 2008-06-20 /pmc/articles/PMC2592270/ /pubmed/19057703 http://dx.doi.org/10.1289/ehp.11229 Text en http://creativecommons.org/publicdomain/mark/1.0/ Publication of EHP lies in the public domain and is therefore without copyright. All text from EHP may be reprinted freely. Use of materials published in EHP should be acknowledged (for example, ?Reproduced with permission from Environmental Health Perspectives?); pertinent reference information should be provided for the article from which the material was reproduced. Articles from EHP, especially the News section, may contain photographs or illustrations copyrighted by other commercial organizations or individuals that may not be used without obtaining prior approval from the holder of the copyright.
spellingShingle Research
Wang, Ting
Moreno-Vinasco, Liliana
Huang, Yong
Lang, Gabriel D.
Linares, Jered D.
Goonewardena, Sascha N.
Grabavoy, Alayna
Samet, Jonathan M.
Geyh, Alison S.
Breysse, Patrick N.
Lussier, Yves A.
Natarajan, Viswanathan
Garcia, Joe G.N.
Murine Lung Responses to Ambient Particulate Matter: Genomic Analysis and Influence on Airway Hyperresponsiveness
title Murine Lung Responses to Ambient Particulate Matter: Genomic Analysis and Influence on Airway Hyperresponsiveness
title_full Murine Lung Responses to Ambient Particulate Matter: Genomic Analysis and Influence on Airway Hyperresponsiveness
title_fullStr Murine Lung Responses to Ambient Particulate Matter: Genomic Analysis and Influence on Airway Hyperresponsiveness
title_full_unstemmed Murine Lung Responses to Ambient Particulate Matter: Genomic Analysis and Influence on Airway Hyperresponsiveness
title_short Murine Lung Responses to Ambient Particulate Matter: Genomic Analysis and Influence on Airway Hyperresponsiveness
title_sort murine lung responses to ambient particulate matter: genomic analysis and influence on airway hyperresponsiveness
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2592270/
https://www.ncbi.nlm.nih.gov/pubmed/19057703
http://dx.doi.org/10.1289/ehp.11229
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