TY - JOUR 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 DO - 10.1183/13993003.00310-2018 VL - 52 IS - 2 SP - 1800310 AU - Alen Faiz AU - Markus Weckmann AU - Haitatip Tasena AU - Corneel J. Vermeulen AU - Maarten Van den Berge AU - Nick H.T. ten Hacken AU - Andrew J. Halayko AU - Jeremy P.T. Ward AU - Tak H. Lee AU - Gavin Tjin AU - Judith L. Black AU - Mehra Haghi AU - Cheng-Jian Xu AU - Gregory G. King AU - Claude S. Farah AU - Brian G. Oliver AU - Irene H. Heijink AU - Janette K. Burgess Y1 - 2018/08/01 UR - http://erj.ersjournals.com/content/52/2/1800310.abstract N2 - 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 ER -