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.authorMacSharry, John
dc.contributor.authorShalaby, Karim H.
dc.contributor.authorMarchica, Cinzia
dc.contributor.authorFarahnak, Soroor
dc.contributor.authorChieh-Li, Tien
dc.contributor.authorLapthorne, Susan
dc.contributor.authorQureshi, Salman T.
dc.contributor.authorShanahan, Fergus
dc.contributor.authorMartin, James G.
dc.contributor.funderScience Foundation Ireland
dc.contributor.funderCanadian Thoracic Society
dc.date.accessioned2016-02-17T11:43:40Z
dc.date.available2016-02-17T11:43:40Z
dc.date.issued2014
dc.description.abstractVarying 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.sponsorshipScience Foundation Ireland (Research Grants; Walton Fellowship; Short Term Travel Fellowship); Canadian Thoracic Society (Studentship)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleide98648
dc.identifier.citationMac 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.doi10.1371/journal.pone.0098648
dc.identifier.issn1932-6203
dc.identifier.issued6en
dc.identifier.journaltitlePLOS ONEen
dc.identifier.urihttps://hdl.handle.net/10468/2334
dc.identifier.volume9en
dc.language.isoenen
dc.publisherPublic Library of Scienceen
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 crediteden
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectKappa-B activationen
dc.subjectAllergic asthmaen
dc.subjectMessenger Rnaen
dc.subjectT cellsen
dc.subjectLung inflammationen
dc.subjectBinding proteinen
dc.subjectDendritic cellsen
dc.subjectResponsesen
dc.subjectExpressionen
dc.subjectIL-5en
dc.titleConcomitant exposure to ovalbumin and endotoxin augments airway inflammation but not airway hyperresponsiveness in a murine model of asthmaen
dc.typeArticle (peer-reviewed)en
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