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

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 (1-100 nM). 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 TNF alpha 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. (C) 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.