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Fluticasone propionate inhibits rhinovirus-induced mucin production via multiple mechanisms in differentiated airway epithelial cells

Mucus hypersecretion contributes to development and progression of various chronic inflammatory airway diseases. Mucus hypersecretion is a characteristic of exacerbations in asthma and COPD, and human rhinovirus (HRV) infections are associated with such exacerbations and have been shown to increase mucin production. The effects of inhaled corticosteroids (ICS) on HRV-induced mucin production are incompletely understood. The aim of the present study was to investigate mechanisms underlying the inhibitory effects of the ICS fluticasone propionate (FP) on HRV-induced mucin production in well-differentiated human primary bronchial epithelial cells (PBEC) cultured at the air–liquid interface (ALI). ALI-PBEC pre-treated with FP were infected by HRV-A16 or HRV-1B and cultures were harvested at 48 h for analysis of cell differentiation, mucin production using qPCR, ELISA and immunofluorescence. Both HRV-A16 and HRV-1B caused a 4-fold increase in MUC5AC gene expression and a 2-fold increase in MUC5AC protein release, accompanied by an increase in the transcription factor SPDEF gene expression. FP caused a 2-3 fold inhibition of these increases. Pre-treatment with the P2R antagonist suramin inhibited HRV-A16-induced MUC5AC gene and protein in ALI-PBEC, suggesting involvement of extracellular ATP in HRV-induced mucin production. Addition of ATP also increased MUC5AC expression by 2-fold, which was inhibited by FP. These data demonstrate that fluticasone propionate treatment confers protection against HRV-induced mucus hypersecretion, which is likely mediated in part by modulating the SPDEF regulatory network and inhibiting extracellular ATP-induced mucin production. This study was supported by a grant from the China Scholarship Council.