Resolvin D1 regulates epithelial ion transport and inflammation in cystic fibrosis airways

Abstract Background Cystic Fibrosis (CF) lung disease is characterised by dysregulated ion transport that promotes chronic bacterial infection and inflammation. The impact of the specialised pro-resolution mediator resolvin D1 (RvD1) on airway surface liquid (ASL) dynamics and innate defence had not yet been investigated in CF airways. Methods Ex vivo studies were performed on primary cultures of alveolar macrophages and bronchial epithelial cells from children with CF and in human bronchial epithelial cell lines; in vivo studies were performed in homozygous F508del-CFTR mice treated with vehicle control or RvD1 (1–100nM). Results RvD1 increased the CF ASL height in human bronchial epithelium and restored the nasal trans-epithelial potential difference in CF mice by decreasing the amiloride-sensitive Na + absorption and stimulating CFTR-independent Cl − secretion. RvD1 decreased TNFα induced IL-8 secretion and enhanced the phagocytic and bacterial killing capacity of human CF alveolar macrophages. Conclusion RvD1 resolves CF airway pathogenesis and has therapeutic potential in CF lung disease.