Chronic inhalation of e-cigarette vapor containing nicotine disrupts airway barrier function and induces systemic inflammation and multiorgan fibrosis in mice
Chronic inhalation of e-cigarette vapor containing nicotine disrupts airway barrier function and induces systemic inflammation and multiorgan fibrosis in mice
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DOI：
10.1152/ajpregu.00270.2017
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发表时间：
2018-06-01
影响因子：
2.8
通讯作者：
Breen, Ellen C.
中科院分区：
文献类型：
--
作者：
Alexander, Laura E. Crotty;Drummond, Christopher A.;Breen, Ellen C.
从理论上讲，电子香烟可能比传统烟草更安全。然而，我们之前的研究表明，电子烟蒸汽（EV）对气道细胞有直接的不良影响，包括降低活力和功能。我们假设反复、慢性吸入EV会降低气道屏障功能，导致炎症蛋白释放到循环中，造成全身炎症状态，最终导致远端器官损伤和功能障碍。C57BL/6和CD-1小鼠每天只暴露于鼻内EV，持续3-6个月，然后进行心肾生理测试。原代人支气管上皮细胞在气液界面培养，每天暴露于EV中15分钟，持续3-5天，然后进行功能测试。每日吸入EV可增加C57BL/6和CD-1小鼠的循环促炎和促纤维化蛋白：血管生成素-1（31倍）和EGF（25倍）增加最多。体外暴露于体外的人气道上皮细胞可重现促炎反应，上皮细胞对感染反应分泌更高的IL-8（分别为227和37 pg/ml， P < 0.05）。体内慢性吸入EV可使肾滤过减少20% （P = 0.017）。纤维化。马氏三色和小红染色显示，小鼠肾脏（1.86倍，C57BL/6； 3.2倍，CD-1, P < 0.05）、心脏（2.75倍，C57BL/6小鼠，P < 0.05）和肝脏（1.77倍，CD-1, P < 0.0001）均升高。基因表达变化表明促纤维化通路激活。吸入EV可改变心血管功能，心率降低（P < 0.01），血压升高（P = 0.016）。这些数据表明，长期吸入EV可能导致炎症加重、器官损伤以及心肾和肝脏疾病。
Electronic (e)-cigarettes theoretically may be safer than conventional tobacco. However, our prior studies demonstrated direct adverse effects of e-cigarette vapor (EV) on airway cells, including decreased viability and function. We hypothesize that repetitive, chronic inhalation of EV will diminish airway barrier function, leading to inflammatory protein release into circulation, creating a systemic inflammatory state, ultimately leading to distant organ injury and dysfunction. C57BL/6 and CD-1 mice underwent nose only EV exposure daily for 3-6 mo. followed by cardiorenal physiological testing. Primary human bronchial epithelial cells were grown at an air-liquid interface and exposed to EV for 15 min daily for 3-5 days before functional testing. Daily inhalation of EV increased circulating proinflammatory and profibrotic proteins in both C57BL/6 and CD-1 mice: the greatest increases observed were in angiopoietin-1 (31-fold) and EGF (25-fold). Proinflammatory responses were recapitulated by daily EV exposures in vitro of human airway epithelium, with EV epithelium secreting higher IL-8 in response to infection (227 vs. 37 pg/ml, respectively; P < 0.05). Chronic EV inhalation in vivo reduced renal filtration by 20% (P = 0.017). Fibrosis. assessed by Masson's trichrome and Picrosirius red staining, was increased in EV kidneys (1.86-fold, C57BL/6; 3.2-fold, CD-1; P < 0.05), heart (2.75-fold, C57BL/6 mice; P < 0.05), and liver (1.77-fold in CD-1; P < 0.0001). Gene expression changes demonstrated profibrotic pathway activation. EV inhalation altered cardiovascular function, with decreased heart rate (P < 0.01), and elevated blood pressure (P = 0.016). These data demonstrate that chronic inhalation of EV may lead to increased inflammation, organ damage, and cardiorenal and hepatic disease.