Alteration of bronchial epithelium host defenses by marijuana and vaping preparations

项目总结 随着娱乐活动合法化的增加，吸食大麻和蒸发大麻在美国呈上升趋势 和医用大麻。大麻中存在的主要精神活性成分，并添加到蒸发中 制剂，为β-9-四氢大麻酚(THC)。即使吸食大麻对梗阻的影响 肺部疾病在不同的研究中可能有所不同，人们认识到吸食大麻与增加 咳嗽、痰和慢性支气管炎通常与感染有关，但其机制仍然存在 待定。我们的初步数据显示，长期单独接触四氢呋喃对人的主要支气管 生长在气液界面的上皮细胞改变了粘液纤毛功能的几个成分(即离子 渠道，纤毛跳动)，导致对感染的易感性增加。环境污染物，如 吸烟，会改变基因表达。不幸的是，一些变化可以在停止的情况下继续存在。 这项研究的目的是确定含有THC的制剂(大麻和蒸发)对 支气管上皮是防御系统的宿主。本提案是针对NOT-DA-20-031“Transcriptomic， 物质使用障碍的表观基因组、调节核糖核酸或功能基因组研究“。在此，我们建议 (1)确定通过大麻烟雾或蒸发长期暴露于THC是否会不同程度地改变 参与宿主防御微生物病原体的支气管上皮功能；以及(2)鉴定性质 停止使用大麻后持续存在的支气管上皮转录改变的研究 烟或蒸气。这项综合研究将揭示大麻烟雾和蒸发物中THC的影响 呼吸道动态平衡的准备和寻找新的分子靶点以预防感染和发展 肺部疾病。

PROJECT SUMMARY Marijuana smoking and vaping is on the rise in the United States with the increased legalization of recreational and medical marijuana. The main psychoactive component present in marijuana, and added to vaping preparations, is delta-9-tetrahydrocannabinol (THC). Even though the effect of marijuana smoking on obstructive lung disease can vary between studies, it is recognized that marijuana smoking is associated with increased cough, sputum production, and chronic bronchitis often associated with infections, but the mechanism remains to be determined. Our preliminary data show that chronic exposure of THC alone to primary human bronchial epithelial cells grown at air-liquid interface alters several components of the mucociliary function (i.e. ion channels, cilia beating), resulting in increased susceptibility to infections. Environmental pollutants, such as cigarette smoking, can alter gene expression. Unfortunately, some of the changes can persist despite cessation. The goal of this study is to determine the effects of THC-containing preparations (marijuana and vaping) on bronchial epithelium host defenses. This proposal is submitted in response to NOT-DA-20-031 “Transcriptomic, epigenomic, regulatory RNA or functional genomic research in substance use disorders”. Here, we propose to (1) determine whether chronic exposures to THC through marijuana smoke or vaping differentially alter the bronchial epithelium functions involved in host defense against microbial pathogens; and (2) identify the nature of transcriptomic changes which persist in bronchial epithelium after cessation from exposures to marijuana smoke or vaping. This comprehensive study will reveal the effects of THC in marijuana smoke and vaping preparations on airway homeostasis and identify new molecular targets to prevent infections and development of lung diseases.