Concomitant exposure to ovalbumin and endotoxin augments airway inflammation but not airway hyperresponsiveness in a murine model of asthma

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dc.contributor.author Mac Sharry, John
dc.contributor.author Shalaby, Karim H.
dc.contributor.author Marchica, Cinzia
dc.contributor.author Farahnak, Soroor
dc.contributor.author Chieh-Li, Tien
dc.contributor.author Lapthorne, Susan
dc.contributor.author Qureshi, Salman T.
dc.contributor.author Shanahan, Fergus
dc.contributor.author Martin, James G.
dc.date.accessioned 2016-02-17T11:43:40Z
dc.date.available 2016-02-17T11:43:40Z
dc.date.issued 2014
dc.identifier.citation Mac Sharry J, Shalaby KH, Marchica C, Farahnak S, Chieh-Li T, Lapthorne S, et al. (2014) Concomitant Exposure to Ovalbumin and Endotoxin Augments Airway Inflammation but Not Airway Hyperresponsiveness in a Murine Model of Asthma. PLoS ONE 9(6): e98648. doi:10.1371/journal.pone.0098648
dc.identifier.volume 9 en
dc.identifier.issued 6 en
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/10468/2334
dc.identifier.doi 10.1371/journal.pone.0098648
dc.description.abstract Varying concentrations of lipopolysaccharide (LPS) in ovalbumin (OVA) may influence the airway response to allergic sensitization and challenge. We assessed the contribution of LPS to allergic airway inflammatory responses following challenge with LPS-rich and LPS-free commercial OVA. BALB/c mice were sensitized with LPS-rich OVA and alum and then underwent challenge with the same OVA (10 µg intranasally) or an LPS-free OVA. Following challenge, bronchoalveolar lavage (BAL), airway responsiveness to methacholine and the lung regulatory T cell population (Treg) were assessed. Both OVA preparations induced BAL eosinophilia but LPS-rich OVA also evoked BAL neutrophilia. LPS-free OVA increased interleukin (IL)-2, IL-4 and IL-5 whereas LPS-rich OVA additionally increased IL-1β, IL-12, IFN-γ, TNF-α and KC. Both OVA-challenged groups developed airway hyperresponsiveness. TLR4-deficient mice challenged with either OVA preparation showed eosinophilia but not neutrophilia and had increased IL-5. Only LPS-rich OVA challenged mice had increased lung Tregs and LPS-rich OVA also induced in vitro Treg differentiation. LPS-rich OVA also induced a Th1 cytokine response in human peripheral blood mononuclear cells. We conclude that LPS-rich OVA evokes mixed Th1, Th2 and innate immune responses through the TLR-4 pathway, whereas LPS-free OVA evokes only a Th2 response. Contaminating LPS is not required for induction of airway hyperresponsiveness but amplifies the Th2 inflammatory response and is a critical mediator of the neutrophil, Th1 and T regulatory cell responses to OVA. en
dc.description.sponsorship Science Foundation Ireland (Research Grants; Walton Fellowship; Short Term Travel Fellowship); Canadian Thoracic Society (Studentship) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Public Library of Science en
dc.rights © 2015 Mac Sharry et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited en
dc.rights.uri http://creativecommons.org/licenses/by/4.0/ en
dc.subject Kappa-B activation en
dc.subject Allergic asthma en
dc.subject Messenger Rna en
dc.subject T cells en
dc.subject Lung inflammation en
dc.subject Binding protein en
dc.subject Dendritic cells en
dc.subject Responses en
dc.subject Expression en
dc.subject IL-5 en
dc.title Concomitant exposure to ovalbumin and endotoxin augments airway inflammation but not airway hyperresponsiveness in a murine model of asthma en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Fergus Shanahan, Alimentary Pharmabotic Centre, University College Cork, Cork, Ireland. +353-21-490-3000 Email: f.shanahan@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.internal.wokid WOS:000338280800003
dc.contributor.funder Science Foundation Ireland
dc.contributor.funder Canadian Thoracic Society
dc.description.status Peer reviewed en
dc.identifier.journaltitle PLOS ONE en
dc.identifier.articleid e98648


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© 2015 Mac Sharry et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Except where otherwise noted, this item's license is described as © 2015 Mac Sharry et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
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