Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner.

Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner.
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DOI:
10.1136/thoraxjnl-2015-208039
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发表时间:
2016-12
期刊:
影响因子:
10
通讯作者:
Foronjy R
Foronjy R
中科院分区:
医学1区
文献类型:
--
作者:
Garcia-Arcos I;Geraghty P;Baumlin N;Campos M;Dabo AJ;Jundi B;Cummins N;Eden E;Grosche A;Salathe M;Foronjy R

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电子烟的使用正在迅速增加,但其对肺部健康的影响尚未确定。检验电子烟使用对肺部健康潜在长期影响的临床研究将需要数十年的时间。为了解决这一知识差距,本研究调查了暴露于雾化的不含尼古丁和含尼古丁的电子烟液对小鼠肺部和正常人呼吸道上皮细胞的影响。让小鼠接触雾化的磷酸盐缓冲盐水、不含尼古丁或含尼古丁的电子烟溶液,每天 1 小时,持续 4 个月。使用 Vitrocell 烟雾暴露机器人将在气液界面培养的正常人支气管上皮 (NHBE) 细胞暴露于电子烟蒸气或尼古丁溶液。吸入含尼古丁的电子烟会增加气道高反应性、远端气隙扩大、粘蛋白产生、细胞因子和蛋白酶表达。接触不含尼古丁的电子烟不会影响这些肺部参数。暴露于含尼古丁电子烟蒸汽的 NHBE 细胞表现出纤毛跳动频率、气道表面液体体积、囊性纤维化跨膜调节器和 ATP 刺激的 K+ 离子电导受损,以及 FOXJ1 和 KCNMA1 表达降低。 NHBE 细胞暴露于尼古丁 5  天会增加白细胞介素 (IL)-6 和 IL-8 的分泌。吸入含尼古丁的电子烟液会引发通常与慢性阻塞性肺病(COPD)发展相关的影响,包括细胞因子表达、气道高反应性和肺组织破坏。这些作用在小鼠肺部和人类气道细胞中均依赖于尼古丁,这表明吸入尼古丁除了具有成瘾性外,还会导致气道和肺部疾病。因此,这些发现强调了电子烟使用过程中吸入尼古丁的潜在危险。
The use of electronic (e)-cigarettes is increasing rapidly, but their lung health effects are not established. Clinical studies examining the potential long-term impact of e-cigarette use on lung health will take decades. To address this gap in knowledge, this study investigated the effects of exposure to aerosolised nicotine-free and nicotine-containing e-cigarette fluid on mouse lungs and normal human airway epithelial cells. Mice were exposed to aerosolised phosphate-buffered saline, nicotine-free or nicotine-containing e-cigarette solution, 1-hour daily for 4 months. Normal human bronchial epithelial (NHBE) cells cultured at an air-liquid interface were exposed to e-cigarette vapours or nicotine solutions using a Vitrocell smoke exposure robot. Inhalation of nicotine-containing e-cigarettes increased airway hyper-reactivity, distal airspace enlargement, mucin production, cytokine and protease expression. Exposure to nicotine-free e-cigarettes did not affect these lung parameters. NHBE cells exposed to nicotine-containing e-cigarette vapour showed impaired ciliary beat frequency, airway surface liquid volume, cystic fibrosis transmembrane regulator and ATP-stimulated K+ ion conductance and decreased expression of FOXJ1 and KCNMA1. Exposure of NHBE cells to nicotine for 5 days increased interleukin (IL)-6 and IL-8 secretion. Exposure to inhaled nicotine-containing e-cigarette fluids triggered effects normally associated with the development of COPD including cytokine expression, airway hyper-reactivity and lung tissue destruction. These effects were nicotine-dependent both in the mouse lung and in human airway cells, suggesting that inhaled nicotine contributes to airway and lung disease in addition to its addictive properties. Thus, these findings highlight the potential dangers of nicotine inhalation during e-cigarette use.
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