Alteration of bronchial epithelium host defenses by marijuana and vaping preparations

项目摘要 随着娱乐性吸烟合法化的增加，美国的吸烟和电子烟正在上升。 和医用大麻大麻中存在的主要精神活性成分，并添加到vaping中 在这些制剂中，最常见的是Δ-9-四氢大麻酚（THC）。尽管吸食大麻对阻塞性肺疾病的影响 肺部疾病可以在研究之间变化，人们认识到，吸食大麻与增加 咳嗽、咳痰和慢性支气管炎常与感染有关，但其机制仍然存在 待定我们的初步数据表明，长期暴露于THC单独的原发性人支气管炎， 在空气-液体界面生长的上皮细胞改变了粘膜纤毛功能的几种成分（即离子 通道，纤毛跳动），导致对感染的易感性增加。环境污染物，如 吸烟可以改变基因表达。不幸的是，有些变化即使停止也会持续下去。 本研究的目的是确定含THC的制剂（大麻和vaping）对 支气管上皮宿主防御。本提案是为了响应NOT-DA-20-031“转录组学， 物质使用障碍的表观基因组、调节RNA或功能基因组研究”。在此，我们建议 (1)确定是否通过大麻烟雾或vaping慢性暴露于THC差异改变 支气管上皮功能参与宿主防御微生物病原体;和（2）确定性质 在停止接触大麻后，支气管上皮细胞中持续存在转录组学变化 吸烟或vaping。这项全面的研究将揭示大麻烟雾和vaping中THC的影响 制备气道内稳态和确定新的分子靶点，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.