National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland; Department of Molecular Medicine RCSI-ERC Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin 9, Ireland.
National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland.
J Cyst Fibros. 2018 Sep;17(5):607-615. doi: 10.1016/j.jcf.2017.11.017. Epub 2017 Dec 8.
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.
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).
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.
RvD1 resolves CF airway pathogenesis and has therapeutic potential in CF lung disease.
囊性纤维化（CF）肺病的特征是离子转运失调，促进慢性细菌感染和炎症。特殊的促解决介质 17-去甲前列腺素 F2α（RvD1）对气道表面液体（ASL）动力学和先天防御的影响尚未在 CF 气道中进行研究。
在来自 CF 儿童的肺泡巨噬细胞和支气管上皮细胞的原代培养物以及人支气管上皮细胞系中进行了离体研究；在接受载体对照或 RvD1（1-100nM）治疗的纯合 F508del-CFTR 小鼠中进行了体内研究。
RvD1 增加了人支气管上皮细胞中的 CF ASL 高度，并通过降低阿米洛利敏感的 Na 吸收和刺激 CFTR 独立的 Cl 分泌，恢复了 CF 小鼠的鼻跨上皮电位差。RvD1 降低了 TNFα 诱导的 IL-8 分泌，并增强了人 CF 肺泡巨噬细胞的吞噬和杀菌能力。
RvD1 解决了 CF 气道发病机制，在 CF 肺疾病中具有治疗潜力。
