Profiling of healthy and asthmatic airway smooth muscle cells following interleukin-1β treatment: A novel role for CCL20 in chronic mucus hypersecretion

Faiz, A; Weckmann, M; Tasena, H; Vermeulen, CJ; Van Den Berge, M; Ten Hacken, NHT; Halayko, AJ; Ward, JPT; Lee, TH; Tjin, G; Black, JL; Haghi, M; Xu, CJ; King, GG; Farah, CS; Oliver, BG; Heijink, IH; Burgess, JK

Profiling of healthy and asthmatic airway smooth muscle cells following interleukin-1β treatment: A novel role for CCL20 in chronic mucus hypersecretion

Weckmann, M Tasena, H Vermeulen, CJ Van Den Berge, M Ten Hacken, NHT Halayko, AJ Ward, JPT Lee, TH Tjin, G Black, JL Haghi, M

Xu, CJ King, GG Farah, CS Oliver, BG

Heijink, IH Burgess, JK

Permalink

Publication Type:: Journal Article
Citation:: European Respiratory Journal, 2018, 52 (2)
Issue Date:: 2018-08-01

Closed Access

	Filename	Description	Size
	CCL20.pdf	Published Version	848.04 kB	Adobe PDF	View/Open

Copyright Clearance Process

Recently Added
In Progress
Closed Access

This item is closed access and not available.

Full metadata record

Field	Value	Language
dc.contributor.author	Faiz, A https://orcid.org/0000-0003-1740-3538	en_US
dc.contributor.author	Weckmann, M	en_US
dc.contributor.author	Tasena, H	en_US
dc.contributor.author	Vermeulen, CJ	en_US
dc.contributor.author	Van Den Berge, M	en_US
dc.contributor.author	Ten Hacken, NHT	en_US
dc.contributor.author	Halayko, AJ	en_US
dc.contributor.author	Ward, JPT	en_US
dc.contributor.author	Lee, TH	en_US
dc.contributor.author	Tjin, G	en_US
dc.contributor.author	Black, JL	en_US
dc.contributor.author	Haghi, M https://orcid.org/0000-0002-3362-1845	en_US
dc.contributor.author	Xu, CJ	en_US
dc.contributor.author	King, GG	en_US
dc.contributor.author	Farah, CS	en_US
dc.contributor.author	Oliver, BG https://orcid.org/0000-0002-7122-9262	en_US
dc.contributor.author	Heijink, IH	en_US
dc.contributor.author	Burgess, JK	en_US
dc.date.available	2018-05-25	en_US
dc.date.issued	2018-08-01	en_US
dc.identifier.citation	European Respiratory Journal, 2018, 52 (2)	en_US
dc.identifier.issn	0903-1936	en_US
dc.identifier.uri	http://hdl.handle.net/10453/132427
dc.description.abstract	© ERS 2018. Chronic mucus hypersecretion (CMH) contributes to the morbidity and mortality of asthma, and remains uncontrolled by current therapies in the subset of patients with severe, steroidresistant disease. Altered cross-talk between airway epithelium and airway smooth muscle cells (ASMCs), driven by pro-inflammatory cytokines such as interleukin (IL)-1β, provides a potential mechanism that influences CMH. This study investigated mechanisms underlying CMH by comparing IL-1β-induced gene expression profiles between asthma and control-derived ASMCs and the subsequent paracrine influence on airway epithelial mucus production in vitro. IL-1β-treated ASMCs from asthmatic patients and healthy donors were profiled using microarray analysis and ELISA. Air-liquid interface (ALI)-cultured CALU-3 and primary airway epithelial cells were treated with identified candidates and mucus production assessed. The IL-1β-induced CCL20 expression and protein release was increased in ASMCs from moderate compared with mild asthmatic patients and healthy controls. IL-1β induced lower MIR146A expression in asthma-derived ASMCs compared with controls. Decreased MIR146A expression was validated in vivo in bronchial biopsies from 16 asthmatic patients versus 39 healthy donors. miR-146a-5p overexpression abrogated CCL20 release in ASMCs. CCL20 treatment of ALI-cultured CALU-3 and primary airway epithelial cells induced mucus production, while CCL20 levels in sputum were associated with increased levels of CMH in asthmatic patients. Elevated CCL20 production by ASMCs, possibly resulting from dysregulated expression of the antiinflammatory miR-146a-5p, may contribute to enhanced mucus production in asthma.	en_US
dc.relation	http://purl.org/au-research/grants/nhmrc/APP1026880
dc.relation.ispartof	European Respiratory Journal	en_US
dc.relation.isbasedon	10.1183/13993003.00310-2018	en_US
dc.subject.classification	Respiratory System	en_US
dc.subject.mesh	Cells, Cultured	en_US
dc.subject.mesh	Epithelial Cells	en_US
dc.subject.mesh	Myocytes, Smooth Muscle	en_US
dc.subject.mesh	Mucus	en_US
dc.subject.mesh	Sputum	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Asthma	en_US
dc.subject.mesh	MicroRNAs	en_US
dc.subject.mesh	Case-Control Studies	en_US
dc.subject.mesh	Gene Expression	en_US
dc.subject.mesh	Adolescent	en_US
dc.subject.mesh	Adult	en_US
dc.subject.mesh	Aged	en_US
dc.subject.mesh	Middle Aged	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Interleukin-1beta	en_US
dc.subject.mesh	Chemokine CCL20	en_US
dc.subject.mesh	Young Adult	en_US
dc.title	Profiling of healthy and asthmatic airway smooth muscle cells following interleukin-1β treatment: A novel role for CCL20 in chronic mucus hypersecretion	en_US
dc.type	Journal Article
utslib.citation.volume	2	en_US
utslib.citation.volume	52	en_US
utslib.for	1101 Medical Biochemistry and Metabolomics	en_US
utslib.for	1116 Medical Physiology	en_US
utslib.for	11 Medical and Health Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Graduate School of Health
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	closed_access
pubs.issue	2	en_US
pubs.publication-status	Published	en_US
pubs.volume	52	en_US

Abstract:

© ERS 2018. Chronic mucus hypersecretion (CMH) contributes to the morbidity and mortality of asthma, and remains uncontrolled by current therapies in the subset of patients with severe, steroidresistant disease. Altered cross-talk between airway epithelium and airway smooth muscle cells (ASMCs), driven by pro-inflammatory cytokines such as interleukin (IL)-1β, provides a potential mechanism that influences CMH. This study investigated mechanisms underlying CMH by comparing IL-1β-induced gene expression profiles between asthma and control-derived ASMCs and the subsequent paracrine influence on airway epithelial mucus production in vitro. IL-1β-treated ASMCs from asthmatic patients and healthy donors were profiled using microarray analysis and ELISA. Air-liquid interface (ALI)-cultured CALU-3 and primary airway epithelial cells were treated with identified candidates and mucus production assessed. The IL-1β-induced CCL20 expression and protein release was increased in ASMCs from moderate compared with mild asthmatic patients and healthy controls. IL-1β induced lower MIR146A expression in asthma-derived ASMCs compared with controls. Decreased MIR146A expression was validated in vivo in bronchial biopsies from 16 asthmatic patients versus 39 healthy donors. miR-146a-5p overexpression abrogated CCL20 release in ASMCs. CCL20 treatment of ALI-cultured CALU-3 and primary airway epithelial cells induced mucus production, while CCL20 levels in sputum were associated with increased levels of CMH in asthmatic patients. Elevated CCL20 production by ASMCs, possibly resulting from dysregulated expression of the antiinflammatory miR-146a-5p, may contribute to enhanced mucus production in asthma.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/132427