Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/32784
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dc.contributor.authorVan Der Velden, J.-
dc.contributor.authorSum, G.-
dc.contributor.authorBarker, D.-
dc.contributor.authorKoumoundouros, E.-
dc.contributor.authorBarcham, G.-
dc.contributor.authorWulff, H.-
dc.contributor.authorCastle, N.-
dc.contributor.authorBradding, Peter-
dc.contributor.authorSnibson, K.-
dc.date.accessioned2015-07-21T11:17:16Z-
dc.date.available2015-07-21T11:17:16Z-
dc.date.issued2013-06-24-
dc.identifier.citationPLoS One, 2013, 8 (6), e66886en
dc.identifier.urihttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0066886en
dc.identifier.urihttp://hdl.handle.net/2381/32784-
dc.description.abstractBACKGROUND: The Ca[superscript: 2+]-activated K[superscript: +] channel K[subscript: Ca]3.1 is expressed in several structural and inflammatory airway cell types and is proposed to play an important role in the pathophysiology of asthma. The aim of the current study was to determine whether inhibition of K[subscript: Ca]3.1 modifies experimental asthma in sheep. METHODOLOGY AND PRINCIPAL FINDINGS: Atopic sheep were administered either 30 mg/kg Senicapoc (ICA-17073), a selective inhibitor of the K[subscript: Ca]3.1-channel, or vehicle alone (0.5% methylcellulose) twice daily (orally). Both groups received fortnightly aerosol challenges with house dust mite allergen for fourteen weeks. A separate sheep group received no allergen challenges or drug treatment. In the vehicle-control group, twelve weeks of allergen challenges resulted in a 60±19% increase in resting airway resistance, and this was completely attenuated by treatment with Senicapoc (0.25±12%; n = 10, P = 0.0147). The vehicle-control group had a peak-early phase increase in lung resistance of 82±21%, and this was reduced by 58% with Senicapoc treatment (24±14%; n = 10, P = 0.0288). Senicapoc-treated sheep also demonstrated reduced airway hyperresponsiveness, requiring a significantly higher dose of carbachol to increase resistance by 100% compared to allergen-challenged vehicle-control sheep (20±5 vs. 52±18 breath-units of carbachol; n = 10, P = 0.0340). Senicapoc also significantly reduced eosinophil numbers in bronchoalveolar lavage taken 48 hours post-allergen challenge, and reduced vascular remodelling. CONCLUSIONS: These findings suggest that K[subscript: Ca]3.1-activity contributes to allergen-induced airway responses, inflammation and vascular remodelling in a sheep model of asthma, and that inhibition of K[subscript: Ca]3.1 may be an effective strategy for blocking allergen-induced airway inflammation and hyperresponsiveness in humans.en
dc.language.isoenen
dc.publisherPublic Library of Scienceen
dc.relation.urihttp://www.ncbi.nlm.nih.gov/pubmed/23826167-
dc.rightsCopyright © 2013 Van Der Velden 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.subjectAcetamidesen
dc.subjectAirway Remodelingen
dc.subjectAirway Resistanceen
dc.subjectAnimalsen
dc.subjectAsthmaen
dc.subjectBlood Vesselsen
dc.subjectBronchoalveolar Lavage Fluiden
dc.subjectCarbacholen
dc.subjectChronic Diseaseen
dc.subjectDisease Models, Animalen
dc.subjectEosinophilsen
dc.subjectFemaleen
dc.subjectIntermediate-Conductance Calcium-Activated Potassium Channelsen
dc.subjectLeukocyte Counten
dc.subjectLungen
dc.subjectMast Cellsen
dc.subjectMuscle, Smoothen
dc.subjectPyroglyphidaeen
dc.subjectSheepen
dc.subjectT-Lymphocytesen
dc.subjectTrityl Compoundsen
dc.titleK(Ca)3.1 channel-blockade attenuates airway pathophysiology in a sheep model of chronic asthma.en
dc.typeJournal Articleen
dc.identifier.doi10.1371/journal.pone.0066886-
dc.identifier.eissn1932-6203-
dc.identifier.piiPONE-D-13-06326-
dc.description.statusPeer-revieweden
dc.description.versionPublisher Versionen
dc.type.subtypeJournal Article;Research Support, Non-U.S. Gov't-
pubs.organisational-group/Organisationen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGYen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicineen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Infection, Immunity and Inflammationen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/Themesen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/Themes/Molecular & Cellular Bioscienceen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/Themes/Respiratory Scienceen
dc.dateaccepted2013-05-12-
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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