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TRP-mediated airway inflammation by e-cigarette vaping

电子烟引起的 TRP 介导的气道炎症

基本信息

批准号：
10247032
负责人：
Matthias A Salathe
金额：
$ 44.96万
依托单位：
UNIVERSITY OF KANSAS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-24 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10247032
关键词：
Acute Adolescent Adverse effects Affect Animal Model Animals Apical Belief Biology CLCA2 gene Cell membrane Cells Chronic Chronic Bronchitis Cinnamon - dietary Complement Cystic Fibrosis Transmembrane Conductance Regulator Data Development Electronic cigarette Epithelial Cells Exposure to Flavoring Functional disorder Goblet Cells Habits Harvest Health High School Student Human Hyperplasia Immune response In Vitro Individual Inflammation Inflammation Mediators Inflammatory Inhalation Ion Channel Knowledge Liquid substance MAP Kinase Gene Mediating Menthol Metaplastic Cell Mucociliary Clearance Mucous body substance Nasal Epithelium Nicotine Nicotinic Receptors Nose Outcome Pathway interactions Physicians Population Propylene Glycols Public Health Recommendation Recording of previous events Reporting Research Risk Risk Reduction Robot Science Sheep Signal Pathway Signal Transduction Site Smoke Smoking System TRP channel TRPA channel Testing Tobacco Tobacco smoking behavior Transforming Growth Factor alpha Transforming Growth Factor beta Vulnerable Populations airway epithelium airway inflammation airway surface liquid base bronchial epithelium cell injury cohort college cytokine design e-cigarette aerosols electronic cigarette use electronic cigarette user electronic liquid electronic vape human subject in vivo mucus hypersecretion multidisciplinary never smoker never smoking nicotine use nicotine vapor non-smoker non-smoking notch protein novel p38 Mitogen Activated Protein Kinase patient population receptor translational study vaping vapor vegetable glycerin vulnerable adolescent

项目摘要

Project Summary Vaping” electronic cigarettes (e-cigs) is believed to be less toxic than smoking tobacco, leading the physician groups such as the Royal College of Physicians to recommended e-cig use as a way to quit tobacco smoking in a risk reduction approach. Such advice, however, may be misinterpreted to imply that vaping has no ill effects upon health, especially for previous never-smokers. In support of this notion, an astonishing 11% percent of never smoking high school students admit to consistent vaping. Unfortunately, there is growing evidence of harm from vaping, including the development of chronic bronchitis. Thus, the potential damage of vaping to never smokers, especially the vulnerable adolescent population, needs to be explored. To this end, this application examines how e-cigarette vapors adversely impact human airways. Data need to establish which e-cig components are most harmful – nicotine, the vaping fluid, or added synthetic flavors – and how they mechanistically exert their effects at the primary target site of inhalation, namely the airway epithelium. To answer these questions, we assembled a multidisciplinary team with expertise in airway biology to study the extent by which e-cig vapor affects airway health. We will investigate the effect of e-cig vapor on airway epithelia in vitro (aim 1), on mucociliary function in a new ovine, large animal model (aim 2), and in a cross- sectional cohort of young never smokers who started to vape (aim 3). The latter group of e-cig users is at greatest risk for harm. Aim 1 will mechanistically examine the signaling pathway of e-cig vapor at the airway epithelium, triggering TRP receptors to stimulate TGF-b1 and Notch signaling to cause mucociliary dysfunction, a hallmark of chronic bronchitis. This aim will be accomplished by exposing fully differentiated airway epithelial cells in vitro to e-cig vapor and its components using sophisticated exposure robots. Aim 2 will confirm the mechanisms studied in vitro in a new, ovine large animal model that allows to examine the effects of vapor components on parameters of mucociliary function and investigate airway inflammation. Finally, aim 3 will examine parameters of mucociliary dysfunction and airway inflammation in young never smokers who started to vape for at least 6 months using a cross sectional design. History of vaping and topography will be assessed in objective ways to correlate with outcomes. This application will therefore mechanistically examine harmful effects of e-cig vapor on airway function and inflammation in a team science approach, going from bench to animal model to human subjects.

项目总结

项目成果

期刊论文数量（22）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

SARS-CoV-2 Mac1 is required for IFN antagonism and efficient virus replication in cell culture and in mice.

DOI：
10.1073/pnas.2302083120
发表时间：
2023-08-29
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
影响因子：
11.1
作者：
Alhammad, Yousef M.;Parthasarathy, Srivatsan;Ghimire, Roshan;Kerr, Catherine M.;O'Connor, Joseph J.;Pfannenstiel, Jessica J.;Chanda, Debarati;Miller, Caden A.;Baumlin, Nathalie;Salathe, Matthias;Unckless, Robert L.;Zuniga, Sonia;Enjuanes, Luis;More, Sunil;Channappanavar, Rudragouda;Fehr, Anthony R.
通讯作者：
Fehr, Anthony R.

Fibroblast growth factor 23 and Klotho contribute to airway inflammation.

DOI：
10.1183/13993003.00236-2018
发表时间：
2018-07
期刊：
The European respiratory journal
影响因子：
0
作者：
Krick S;Grabner A;Baumlin N;Yanucil C;Helton S;Grosche A;Sailland J;Geraghty P;Viera L;Russell DW;Wells JM;Xu X;Gaggar A;Barnes J;King GD;Campos M;Faul C;Salathe M
通讯作者：
Salathe M

Nebulized Menthol Impairs Mucociliary Clearance via TRPM8 and MUC5AC/MUC5B in Primary Airway Epithelial Cells.

DOI：
10.3390/ijms24021694
发表时间：
2023-01-15
期刊：
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
影响因子：
5.6
作者：
Baumlin, Nathalie;Silswal, Neerupma;Dennis, John S.;Niloy, Asef J.;Kim, Michael D.;Salathe, Matthias
通讯作者：
Salathe, Matthias

Rebuttal from Samuel Chung, Charles D. Bengtson, Michael D. Kim and Matthias Salathe.

DOI：
10.1113/jp280093
发表时间：
2020-08
期刊：
The Journal of physiology
影响因子：
0
作者：
Chung S;Bengtson CD;Kim MD;Salathe M
通讯作者：
Salathe M

A long noncoding RNA antisense to ICAM-1 is involved in allergic asthma associated hyperreactive response of airway epithelial cells.

DOI：
10.1038/s41385-020-00352-9
发表时间：
2021-05
期刊：
Mucosal immunology
影响因子：
8
作者：
Devadoss D;Daly G;Manevski M;Houserova D;Hussain SS;Baumlin N;Salathe M;Borchert GM;Langley RJ;Chand HS
通讯作者：
Chand HS