Resolvin D1 regulates epithelial ion transport and inflammation in cystic fibrosis airways.
Resolvin D1 regulates epithelial ion transport and inflammation in cystic fibrosis airways.
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DOI：
10.1016/j.jcf.2017.11.017
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发表时间：
2017-12
期刊：
影响因子：
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通讯作者：
F. Ringholz;G. Higgins;A. Hatton;A. Sassi;A. Moukachar;C. Fustero-Torre;M. Hollenhorst;I. Sermet-Gaudelus;B. Harvey;P. McNally;V. Urbach
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文献类型：
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作者：
F. Ringholz;G. Higgins;A. Hatton;A. Sassi;A. Moukachar;C. Fustero-Torre;M. Hollenhorst;I. Sermet-Gaudelus;B. Harvey;P. McNally;V. Urbach
囊性纤维化（CF）肺部疾病的特征是离子转运失调，促进慢性细菌感染和炎症。专门的前分辨率调解人resolvin D1（RvD 1）对气道表面液体（ASL）的动力学和先天性防御的影响尚未调查CF airways.MethodsEx vivostudies进行了原代培养的肺泡巨噬细胞和支气管上皮细胞从儿童CF和人支气管上皮细胞系;在用载体对照或RvD 1处理的纯合F508 del-CFTR小鼠中进行体内研究结果RvD 1可增加人支气管上皮细胞CF ASL高度，并恢复经鼻给药后的气道上皮细胞CF ASL高度。通过降低阿米洛利敏感性Na+吸收和刺激CFTR非依赖性Cl−分泌，在CF小鼠中增加上皮电位差。结论RvD 1可降低TNFα诱导的人CF肺泡巨噬细胞IL-8的分泌，增强其吞噬和杀菌能力。
BackgroundCystic 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.MethodsEx vivostudies were performed on primary cultures of alveolar macrophages and bronchial epithelial cells from children with CF and in human bronchial epithelial cell lines;in vivostudies were performed in homozygous F508del-CFTR mice treated with vehicle control or RvD1 (1–100 nM).ResultsRvD1 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.ConclusionRvD1 resolves CF airway pathogenesis and has therapeutic potential in CF lung disease.