Effect of long-term corticosteroid treatment on microRNA and gene-expression profiles in Chronic Obstructive Pulmonary Disease

Abstract

To investigate whether microRNA (miRNA) expression is modulated by inhaled corticosteroid (ICS) treatment, we performed genome-wide miRNA analysis on bronchial biopsies of 69 moderate/severe COPD patients at baseline and after 6- and 30-month treatment with the ICS fluticasone propionate (FP) or placebo. The effect of ICS on miRNA expression was validated in differentiated primary bronchial epithelial cultures, and functional studies were conducted in BEAS-2B cells. MiRNAs affected by ICS and their predicted targets were compared to an independent miRNA dataset of bronchial brushings from COPD patients and healthy controls. Treatment with ICS for both 6- and 30-months significantly altered the expression of 4 miRNAs, including miR-320d, which was increased during ICS treatment compared with placebo. The ICS-induced increase of miR-320d was confirmed in primary airway epithelial cells. MiR-320d negatively correlated targets were enriched for pro-inflammatory genes and were increased in the bronchial brushes of patients with lower lung function in the independent dataset. Overexpression of miR-320d in BEAS-2B cells dampened cigarette smoke extract-induced pro-inflammatory activity via inhibition of nuclear factor (NF)-κB. Collectively, we identified miR-320d as a novel mediator of ICS, regulating the pro-inflammatory response of the airway epithelium.