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.
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| http://dx.doi.org/10.1016/j.jcf.2017.11.017 | DOI Listing |
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