We previously showed that miR-320d is increased in bronchial biopsies from COPD patients upon corticosteroid treatment for 6 or 30 months and is negatively correlated with pro-inflammatory gene expression (Faiz et al. Eur Respir J 2019; 53:4). We hypothesize that miR-320d has an anti-inflammatory role in airway epithelium. Our aim was to investigate the role of miR-320d in the pathogenesis of COPD and to investigate the effect of miR-320d overexpression on cigarette smoke extract (CSE)-induced pro-inflammatory responses in airway epithelial cells (AECs). MiR-320d expression was assessed in lung tissue from two cohorts of mild to severe COPD patients (n=38-40) and smoking matched controls (n=33-52) and in AECs from 6 severe COPD and 6 non-COPD subjects exposed to 20% CSE using qPCR. AECs were transfected with 1nM miR-320d mimic, treated with 20% CSE for 24h and the secretion of CXCL8 was measured in cell supernatants using ELISA. MiR-320d expression was significantly lower in lung tissue from COPD patients compared to controls. Upon 6 hours CSE exposure, a trend towards increased levels of miR-320d was observed in non-COPD-derived AECs, while a significant increase in miR-320d expression was measured in COPD-derived AECs. 24 hours exposure to CSE induced miR-320d expression in non-COPD-derived AECs, but no longer in COPD-derived AECs. Furthermore, overexpression of miR-320d reduced CXCL8 levels in non-COPD-derived AECs, but not in COPD-derived AECs. In conclusion, miR-320d expression is lower in lung tissue of COPD patients compared to controls. The induction and the anti-inflammatory effect of miR-320d on epithelial cytokine release differed in AECs derived from non-COPD compared to COPD, suggesting that this could contribute to the dysregulated inflammatory response in COPD.
