Airway smooth muscle may drive mucus hypersecretion in asthma James G. Martin 1,2 Affiliations: 1 Dept of Medicine, Division of Respiratory Medicine, Faculty of Medicine, McGill University, Montreal, QC, Canada . 2 Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Montreal, QC, Canada. Correspondence: James G. Martin, Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, 1001 Decarie Blvd, Montreal, QC, H4A 3J1, Canada. E-mail: james.martin@mcgill.ca @ERSpublications New insights into a potential property of airway smooth muscle cells with relevance to asthma http://ow.ly/uVe030kPoNN Cite this article as: Martin JG. Airway smooth muscle may drive mucus hypersecretion in asthma. Eur Respir J 2018; 52: 1801166 [https://doi.org/10.1183/13993003.01166-2018]. The contribution of airway smooth muscle (ASM) to asthma is critical but the multiple ways in which it may contribute to its pathobiology is still an active area of exploration. Contractile, proliferative and secretory properties relevant to asthma have been assessed. To date, studies of the contractile properties of isolated ASM have failed to demonstrate alterations in contractile properties that could explain excessive airway narrowing and airway hyperresponsiveness [1, 2], however tempting it is to attribute these features of asthma to intrinsic abnormalities of the muscle. In contrast to studies of tissue strips, cultured ASM cells demonstrate a range of “pro-asthmatic” properties that differ between cells derived from asthmatic subjects and healthy controls. For example, cultured ASM cells show enhanced stiffening when stimulated with contractile agonists [3] and proliferate more rapidly when treated with growth factors [4, 5], a property that would potentially favour a predisposition to remodelling. The pro-inflammatory phenotype is manifest as the expression of cytokines such as the neutrophilic chemoattractant CXCL8, attributable to enhanced NF-κB binding to the promoter site of CXCL8 [6]. Matrix proteins affecting ASM function and other cellular phenotypes are also secreted by ASM and are determinant of the ASM phenotype (reviewed in [7]). In the current issue of the European Respiratory Journal,FAIZ et al. [8] describe an elegant series of studies using in vitro techniques to study the effects of interleukin (IL)-1β on ASM cells, coupled with the analysis of sputum samples from human asthmatics, which have led to the conclusion that ASM cells contribute to mucus hypersecretion by the epithelium. An examination of gene expression profiles of ASM cells harvested from asthmatic and healthy subjects stimulated with IL-1β revealed that CCL20 and MIR146A were among the genes whose expression was affected by the cytokine. MIR146A was differentially regulated in ASM cells harvested from moderate asthmatics, with a lesser increase in expression and concurrently a greater increase in CCL20 protein secretion by the ASM cells compared to mild asthmatics and healthy controls. The gene product miR-146a-5p was linked to the regulation of the expression of CCL20 by showing that CCL20 expression was reduced by overexpression of miR-146a-5p in the ASM cells. Recombinant CCL20 applied to airway epithelial cells induced mucus production and is a postulated cause of chronic mucus hypersecretion in asthma. The increased level of CCL20 in the sputum of asthmatics provides evidence to support plausibility of the hypothesis. Received: June 20 2018 | Accepted: July 02 2018 Copyright ©ERS 2018 https://doi.org/10.1183/13993003.01166-2018 Eur Respir J 2018; 52: 1801166 | EDITORIAL BASIC SCIENCE