RT Journal Article
SR Electronic
T1 Profiling of healthy and asthmatic airway smooth muscle cells following interleukin-1β treatment: a novel role for CCL20 in chronic mucus hypersecretion
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1800310
DO 10.1183/13993003.00310-2018
VO 52
IS 2
A1 Alen Faiz
A1 Markus Weckmann
A1 Haitatip Tasena
A1 Corneel J. Vermeulen
A1 Maarten Van den Berge
A1 Nick H.T. ten Hacken
A1 Andrew J. Halayko
A1 Jeremy P.T. Ward
A1 Tak H. Lee
A1 Gavin Tjin
A1 Judith L. Black
A1 Mehra Haghi
A1 Cheng-Jian Xu
A1 Gregory G. King
A1 Claude S. Farah
A1 Brian G. Oliver
A1 Irene H. Heijink
A1 Janette K. Burgess
YR 2018
UL http://erj.ersjournals.com/content/52/2/1800310.abstract
AB 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, steroid-resistant 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 anti-inflammatory miR-146a-5p, may contribute to enhanced mucus production in asthma.Elevated levels of CCL20 contribute to enhanced mucus hypersecretion in asthma http://ow.ly/m7F830ko3Rb