Deoxyribonuclease 1 reduces pathogenic effects of cigarette smoke exposure in the lung.
Deoxyribonuclease 1 reduces pathogenic effects of cigarette smoke exposure in the lung.
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DOI：
10.1038/s41598-017-12474-5
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发表时间：
2017-09-21
影响因子：
4.6
通讯作者：
Bardin PG
中科院分区：
文献类型：
--
作者：
King PT;Sharma R;O'Sullivan KM;Callaghan J;Dousha L;Thomas B;Ruwanpura S;Lim S;Farmer MW;Jennings BR;Finsterbusch M;Brooks G;Selemidis S;Anderson GP;Holdsworth SR;Bardin PG
我们的目的是研究脱氧核糖核酸酶（DNase） 1是否是一种潜在的治疗剂，以减少香烟烟雾暴露在肺部的致病作用。吸烟引起蛋白酶失衡，产生过多蛋白酶，这是肺气肿发病的关键过程。造成这种效果的机制还没有明确定义。我们在体外和体内的研究表明，香烟烟雾显著增加中性粒细胞和巨噬细胞胞外陷阱的表达，并共同表达致病蛋白酶、中性粒细胞弹性蛋白酶和基质金属蛋白酶9和12。通过添加DNase 1，这种对香烟烟雾的反应显著减少，DNase 1也显著减少巨噬细胞数量和肺蛋白水解。DNase 1是目前临床使用的一种治疗方法，可以减少香烟烟雾的致病作用。
Our aim was to investigate if deoxyribonuclease (DNase) 1 is a potential therapeutic agent to reduce pathogenic effects of cigarette smoke exposure in the lung. Cigarette smoke causes protease imbalance with excess production of proteases, which is a key process in the pathogenesis of emphysema. The mechanisms responsible for this effect are not well-defined. Our studies demonstrate both in vitro and in vivo that cigarette smoke significantly increases the expression of neutrophil and macrophage extracellular traps with coexpression of the pathogenic proteases, neutrophil elastase and matrix metalloproteinases 9 and 12. This response to cigarette smoke was significantly reduced by the addition of DNase 1, which also significantly decreased macrophage numbers and lung proteolysis. DNase 1, a treatment currently in clinical use, can diminish the pathogenic effects of cigarette smoke.
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