Effect of cigarette smoke extract and Th17 cytokine on production of inflammatory cytokines and chemokines in human airway smooth muscle cells

Background: Cigarette smoke (CS) plays an important role in airway inflammation in asthma. IL-17A is the major cytokine secreted by Th17 cells and induces production of many inflammatory cytokine and chemokine from different cell types. This study aims to assess the effect of CSE and IL-17A on production of inflammatory cytokines and chemokines in human airway smooth muscle cells (HASMCs) and to explore the effect of CS on IL-17A-stimulated production of inflammatory cytokines and chemokines. Methods: CS extract (CSE) was prepared from the smoke of two research cigarettes bubbled into 20 ml of cell culture medium. Confluent and growth-arrested HASMCs were pre-treated with and without CSE (3.5%) for 24h prior to incubation with CSE, IL-17A (10 ng/ml), or CSE + IL17A for 24h. Cytokines and chemokines were measured in the collected medium using Bio-Plex Pro-Human Cytokine 27-plex assay. Results: CSE induced production of neutrophilic chemoattractant CXCL-8 but inhibited production of Th2 cytokines (IL-4 and IL-13 but had no effect on IL-5), eosinophilic chemokines (Eotaxin, IP-10 and RANTES) and IL-17A in HASMCs. Interestingly, IL-17A stimulated production of IL-8, Th2 cytokines and eosinophil chemokines. CSE inhibited IL-17A-indcued production of Th2 cytokines and eosinophilic chemokines but significantly increased IL-17A-induced production of IL-8 (11.2-fold higher than IL-17A alone). Conclusion: Our findings suggest CS may supress eosinophilic airway inflammation and promote neutrophilic airway inflammation in asthma. IL-17A may contribute to neutrophilic as well as eosinophilic airway inflammation in asthma.