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

Alen Faiz*, Markus Weckmann, Haitatip Tasena, Corneel J. Vermeulen, Maarten Van den Berge, Nick H. T. ten Hacken, Andrew J. Halayko, Jeremy P. T. Ward, Tak H. Lee, Gavin Tjin, Judith L. Black, Mehra Haghi, Cheng Jian Xu, Gregory G. King, Claude S. Farah, Brian G. Oliver, Irene H. Heijink, Janette K. Burgess

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number1800310
Pages (from-to)1-12
Number of pages12
JournalEuropean Respiratory Journal
Volume52
Issue number2
DOIs
Publication statusPublished - 1 Aug 2018
Externally publishedYes

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