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dc.contributor.authorChen, Alice C-H
dc.contributor.authorTran, Hai B
dc.contributor.authorXi, Yang
dc.contributor.authorYerkovich, Stephanie T
dc.contributor.authorBaines, Katherine J
dc.contributor.authorPizzutto, Susan J
dc.contributor.authorCarroll, Melanie
dc.contributor.authorRobertson, Avril AB
dc.contributor.authorCooper, Matthew A
dc.contributor.authorSchroder, Kate
dc.contributor.authorSimpson, Jodie L
dc.contributor.authorGibson, Peter G
dc.contributor.authorHodge, Greg
dc.contributor.authorMasters, Ian B
dc.contributor.authorBuntain, Helen M
dc.contributor.authorPetsky, Helen L
dc.contributor.authorPrime, Samantha J
dc.contributor.authorChang, Anne B
dc.contributor.authorHodge, Sandra
dc.contributor.authorUpham, John W
dc.date.accessioned2019-09-23T00:39:36Z
dc.date.available2019-09-23T00:39:36Z
dc.date.issued2018
dc.identifier.issn2312-0541
dc.identifier.doi10.1183/23120541.00130-2017
dc.identifier.urihttp://hdl.handle.net/10072/387611
dc.description.abstractProtracted bacterial bronchitis (PBB) in young children is characterised by prolonged wet cough, prominent airway interleukin (IL)-1β expression and infection, often with nontypeable Haemophilus influenzae (NTHi). The mechanisms responsible for IL-1-driven inflammation in PBB are poorly understood. We hypothesised that the inflammation in PBB involves the NLRP3 and/or AIM2 inflammasome/IL-1β axis. Lung macrophages obtained from bronchoalveolar lavage (BAL), peripheral blood mononuclear cells (PBMCs), blood monocytes and monocyte-derived macrophages from patients with PBB and age-matched healthy controls were cultured in control medium or exposed to live NTHi. In healthy adult PBMCs, CD14+ monocytes contributed to 95% of total IL-1β-producing cells upon NTHi stimulation. Stimulation of PBB PBMCs with NTHi significantly increased IL-1β expression (p<0.001), but decreased NLRC4 expression (p<0.01). NTHi induced IL-1β secretion in PBMCs from both healthy controls and patients with recurrent PBB. This was inhibited by Z-YVAD-FMK (a caspase-1 selective inhibitor) and by MCC950 (a NLRP3 selective inhibitor). In PBB BAL macrophages inflammasome complexes were visualised as fluorescence specks of NLRP3 or AIM2 colocalised with cleaved caspase-1 and cleaved IL-1β. NTHi stimulation induced formation of specks of cleaved IL-1β, NLRP3 and AIM2 in PBMCs, blood monocytes and monocyte-derived macrophages. We conclude that both the NLRP3 and AIM2 inflammasomes probably drive the IL-1β-dominated inflammation in PBB.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherEuropean Respiratory Society (ERS)
dc.relation.ispartofpagefrom1
dc.relation.ispartofpageto11
dc.relation.ispartofissue1
dc.relation.ispartofjournalERJ Open Research
dc.relation.ispartofvolume4
dc.titleMultiple inflammasomes may regulate the interleukin-1-driven inflammation in protracted bacterial bronchitis
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationChen, AC-H; Tran, HB; Xi, Y; Yerkovich, ST; Baines, KJ; Pizzutto, SJ; Carroll, M; Robertson, AAB; Cooper, MA; Schroder, K; Simpson, JL; Gibson, PG; Hodge, G; Masters, IB; Buntain, HM; Petsky, HL; Prime, SJ; Chang, AB; Hodge, S; Upham, JW, Multiple inflammasomes may regulate the interleukin-1-driven inflammation in protracted bacterial bronchitis., ERJ Open Research, 2018, 4 (1), pp. 1-11
dcterms.dateAccepted2018-02-08
dcterms.licensehttps://creativecommons.org/licenses/by-nc/4.0/
dc.date.updated2019-09-23T00:33:46Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© ERS 2018. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0 (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorPetsky, Helen


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