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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要随着娱乐合法化程度的提高，美国吸食大麻和吸电子烟的人数呈上升趋势和医用大麻是大麻中存在的主要精神活性成分，并添加到电子烟中。制剂，是δ-9-四氢大麻酚（THC），尽管吸食大麻对阻塞有影响。不同研究之间的肺部疾病可能有所不同，但人们认识到吸食大麻与肺部疾病增加有关。咳嗽、咳痰和慢性支气管炎通常与感染有关，但其机制仍然存在我们的初步数据表明，单独长期暴露于人类初级支气管。在空气-液体界面生长的上皮细胞改变了粘液纤毛功能的几个组成部分（即离子通道，纤毛跳动），导致对环境污染物的易感性增加，例如感染。不幸的是，即使戒烟，某些变化仍会持续存在。本研究的目的是确定含 THC 的制剂（大麻和电子烟）对该提案是为了回应 NOT-DA-20-031“转录组学，在此，我们建议对物质使用障碍进行表观基因组、调节性 RNA 或功能基因组研究”。 (1) 确定通过大麻烟雾或电子烟长期接触 THC 是否会不同程度地改变支气管上皮功能参与宿主针对微生物病原体的防御；以及（2）确定其性质；停止接触大麻后支气管上皮中持续存在的转录组变化这项综合研究将揭示 THC 对大麻烟雾和电子烟的影响。准备气道稳态并确定新的分子靶标以预防感染和发育肺部疾病。