Alteration of bronchial epithelium host defenses by marijuana and vaping preparations

大麻和电子烟制剂改变支气管上皮宿主防御

• 批准号: 10753830
• 负责人: Estelle A Cormet-Boyaka
• 金额: $ 19.69万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10753830
• 关键词: Acute; Air; Apical; Bacteria; Bacterial Infections; Behavior; CNR1 gene; CNR2 gene; Cannabidiol; Cannabinoids; Cell Proliferation; Cells; Chronic; Chronic Bronchitis; Cigarette; Cilia; Coughing; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Data; Devices; Electronic cigarette; Environmental Pollutants; Epithelial Cells; Excision; Exposure to; Frequencies; Gene Expression; Genes; Goals; Goblet Cells; Health; Homeostasis; Host Defense; Human; Hydration status; Hyperplasia; Impairment; In Vitro; Infection; Infection prevention; Inhalation; Ion Channel; Legal; Liquid substance; Long-Term Effects; Lung; Lung diseases; Marijuana; Marijuana Smoking; Measures; Medical Marijuana; Metaplasia; Modeling; Molecular; Molecular Target; Mucociliary Clearance; Mucous body substance; National Institute of Drug Abuse; Nature; Obstructive Lung Diseases; Outcome; Pathway Analysis; Pathway interactions; Patients; Peptides; Persons; Predisposition; Preparation; Primary Ciliary Dyskinesias; Production; Proteins; Proteomics; Psychotropic Drugs; RNA; Recovery; Recreation; Research; Research Project Grants; Rheology; Risk; Role; Secretory Cell; Smoker; Smoking; Sputum; Staphylococcus aureus infection; Substance Use Disorder; System; THC exposure; Teenagers; Testing; Tetrahydrocannabinol; Tobacco smoking behavior; US State; United States; United States National Institutes of Health; Virus; Virus Diseases; airway epithelium; antimicrobial; antimicrobial drug; bronchial epithelium; cannabinoid receptor; cigarette smoking; differential expression; epigenomics; exposure to cigarette smoke; functional genomics; in vivo; lung development; marijuana smoke; marijuana use; marijuana vaping; methicillin resistant Staphylococcus aureus; particle; pathogen; pathogenic microbe; response; transcriptome sequencing; transcriptomics; treatment effect; vaping; vaping THC

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.

项目摘要 随着娱乐活动的合法化，大麻吸烟和烟雾正在上升 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 准备工作是Delta-9-四氢大麻酚（THC）。即使大麻吸烟对阻塞性的影响 研究之间的肺病可能有所不同，人们认识到大麻吸烟与增加有关 咳嗽，痰液产生和慢性支气管炎通常与感染有关，但该机制仍然存在 要确定。我们的初步数据表明，单独使用THC的长期暴露于原发性支气管 在空气界面生长的上皮细胞改变了粘膜函数的几个成分（即离子 频道，纤毛击败），导致对感染的敏感性增加。环境污染物，例如 吸烟，可以改变基因表达。不幸的是，某些更改可以持续暂停。 这项研究的目的是确定含THC的制剂（大麻和Vapi​​ng）对 支气管上皮宿主防御。该提案是针对NOT-DA-20-031的“转录组”提交的 表观基因组学，调节性RNA或功能性基因组研究障碍”。在这里，我们建议 （1）确定长期通过大麻烟暴露于THC还是对 宿主防御微生物病原体涉及的支气管上皮功能； （2）确定性质 从暴露到大麻后，持续支气管上皮的转录组变化 烟雾或烟。这项全面的研究将揭示THC在大麻烟雾和烟中的影响 在气道体内稳态上的准备并确定新的分子靶标，以防止感染和发育 肺部疾病。