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Age-Dependent Effects of E-cigarette Vaping on Host Pathogen Defense

电子烟对宿主病原体防御的年龄依赖性影响

基本信息

批准号：
10199091
负责人：
Christopher Michael Royer
金额：
$ 14.75万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-15 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10199091
关键词：
Address Adolescence Adolescent Adult Advisory Committees Affect Age Asthma Bacterial Infections Binding Biomedical Research Cell Culture Techniques Cellular biology Child Chronic Obstructive Airway Disease Comparative Study Complement Data Defense Mechanisms Development Disease Doctor of Philosophy Electronic cigarette Endotoxins Environment Epidemiology Epithelial Epithelial Cells Exhibits Foundations Funding Future Goals Grant Host Defense Host Defense Mechanism Human Immune Immunology Impairment In Vitro Infant Infection Inflammation Inflammatory Inhalation Exposure Investigation Knock-out Knowledge Lipopolysaccharides Lung Lung Inflammation Lung diseases Macaca mulatta Mentored Research Scientist Development Award Mentors Methods Modeling Molecular Molecular Biology Mucous Membrane Mus Nasal Epithelium Obstructive Lung Diseases Oxidative Stress Palate Pattern Physiology Play Predisposition Primates Process Proteins Regulation Reporting Research Research Personnel Resource Development Resources Respiratory Tract Infections Risk Risk Estimate Rodent Rodent Model Role Safety Secure Signal Transduction Smoker Smoking Stimulus Structure System Therapeutic Time Training Transgenic Organisms Viral Writing age related airway epithelium airway inflammation base career career development cigarette smoke combustible cigarette e-cigarette aerosols electronic cigarette use experience experimental study exposure to cigarette smoke high school immature animal in vivo innate immune function interest lung development mature animal microbial mimetics mouse model nonhuman primate novel therapeutics overexpression pathogen pathogenic bacteria pathogenic virus programs response vaping

项目摘要

7. Project Summary/Abstract Electronic cigarettes have rapidly gained popularity and have a widened base among adolescents due to their perceived safety over traditional cigarettes. Epidemiological estimates indicate electronic cigarette vapor (ECV) carries a risk for asthma in young people whereas it may be too early to estimate risk for chronic obstructive pulmonary disease (COPD). Traditional cigarette smoke (CS) contributes strongly to COPD and suppresses host defenses increasing susceptibility to infection. Rodent models indicate similar susceptibility due to ECV. How children and adolescents respond to both CS and ECV, relative to adults, remains poorly understood. Airway epithelia form a structural barrier but also secrete numerous proteins into the airway that protect the lung from the environment and form part of the innate mucosal defense. The innate mucosal defense system of the lung is affected by CS and ECV however how dysregulation of these defenses contributes to lung disease is not clear. It is also unclear whether the age at exposure independently contributes to disease. The overarching hypothesis for this project is that ECV modulates the airway epithelial response to environmental stimuli through the effects on innate mucosal defense proteins. We will address the hypothesis through three specific aims in which we will also compare ECV to the more widely studied CS. In Aim 1 we will determine the effects of ECV in airway epithelial cells from infant, adolescent, and adult nonhuman primates. We will assess the effects of the exposures on the innate mucosal defenses as well as the regulation of inflammation in the epithelia. In Aim 2 we will examine the effects of changing levels and function of one of the most abundantly expressed innate mucosal defense proteins, SPLUNC1. We will stimulate airway epithelia with molecules that are surrogates for microbial infection and examine the regulation of the response of epithelia by different levels and functional activity of SPLUNC1. In Aim 3 we will compare the effects of CS and ECV in a mouse model. Within this model we will vary the levels of SPLUNC1 to determine its ability to regulate inflammation during these exposures and following a challenge with a surrogate molecule for bacterial infection. We will further determine if SPLUNC1 function can be rescued following CS and ECV exposure by administration directly to the lungs. SPLUNC1 is a promising candidate as a new class of therapeutics and these experiments will help determine its efficacy. The candidate, Christopher Royer, DVM, PhD, seeks to (1) gain knowledge and practical experience in mechanistic, hypothesis- driven research through pertinent in vitro methods and rodent models and (2) receive mentored training in scientific writing, research program management, and grantsmanship leading to successful application for R01- level research funding. The SERCA K01 will provide protected time to achieve these objectives and the means to secure preliminary data for future grants launching Dr. Royer's independent biomedical research career.

7. 项目总结/文摘