Dissociation of inflammatory and epithelial responses in a murine model of chronic asthma

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dc.contributor.authorFoster, Paul S
dc.contributor.authorYang, Ming
dc.contributor.authorMatthaei, Klaus
dc.contributor.authorYoung, I M
dc.contributor.authorTemelkovski, J
dc.contributor.authorKumar, Rakesh K
dc.date.accessioned2015-12-13T23:17:40Z
dc.date.issued2000
dc.date.updated2015-12-12T08:53:58Z
dc.description.abstractTo study pathogenetic mechanisms in chronic asthma, we employed a novel experimental model that replicates characteristic features of the human disease. Chronic inflammation and epithelial changes, specifically localized to the airways, were induced by repeated exposure of systemically sensitized BALB/c mice to low mass concentrations of aerosolized ovalbumin for 6 weeks. The contribution of Th2 cytokine-driven inflammation to the development of airway lesions and hyperreactivity was assessed in cytokine-deficient mice. In interleukin-5-deficient animals, intraepithelial eosinophils and chronic inflammatory cells in the lamina propria of the airways were markedly decreased; however, these animals developed epithelial hypertrophy and subepithelial fibrosis comparable with that observed in sensitized wild type mice. Airway hyperreactivity to inhaled methacholine did not develop in interleukin-5-deficient mice. In contrast, interleukin-4-deficient mice exhibited no decrease in airway inflammation, but had significantly greater epithelial hypertrophy and subepithelial fibrosis, as well as exaggerated hyperreactivity to methacholine. We conclude that interleukin-5, but not interleukin-4, plays a central role in the development of chronic inflammation of the airways and the induction of airway hyperreactivity. Furthermore, chronic epithelial and fibrotic changes occur independently of interleukin-5 and are not required for the development of airway hyperreactivity. The dissociation between airway wall remodeling and airway hyperreactivity has important implications for therapeutic approaches to chronic asthma.
dc.identifier.issn0023-6837
dc.identifier.urihttp://hdl.handle.net/1885/89818
dc.publisherLippincott Williams & Wilkins
dc.sourceLaboratory Investigation
dc.subjectKeywords: cytokine; interleukin 4; interleukin 5; methacholine; animal experiment; animal model; animal tissue; article; asthma; bronchus hyperreactivity; chronic inflammation; controlled study; cytokine release; eosinophil; experimental model; fibrosis; hypertroph
dc.titleDissociation of inflammatory and epithelial responses in a murine model of chronic asthma
dc.typeJournal article
local.bibliographicCitation.lastpage662
local.bibliographicCitation.startpage655
local.contributor.affiliationFoster, Paul S, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationYang, Ming, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationMatthaei, Klaus, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationYoung, I M, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationTemelkovski, J, University of New South Wales
local.contributor.affiliationKumar, Rakesh K, University of New South Wales
local.contributor.authoremailu8200697@anu.edu.au
local.contributor.authoruidFoster, Paul S, u8800551
local.contributor.authoruidYang, Ming, u4003214
local.contributor.authoruidMatthaei, Klaus, u8200697
local.contributor.authoruidYoung, I M, u9817141
local.description.embargo2037-12-31
local.description.notesImported from ARIES
local.description.refereedYes
local.identifier.absfor110203 - Respiratory Diseases
local.identifier.ariespublicationMigratedxPub20037
local.identifier.citationvolume80
local.identifier.scopusID2-s2.0-0034079382
local.identifier.uidSubmittedByMigrated
local.type.statusPublished Version

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