权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Pulmonary response to nanomaterial-ozone exposures

对纳米材料臭氧暴露的肺部反应

基本信息

批准号：
10056687
负责人：
CHRISTINE K PAYNE
金额：
$ 24.15万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10056687
关键词：
A549 Affect Air Pollutants Air Pollution Biological Biological Assay Biological Models Bronchoalveolar Lavage Fluid Carbon Nanotubes Cell Culture Techniques Cell physiology Cells Collaborations Comet Assay Complex Cosmetics Coupled Critical Care Cultured Cells DNA Damage Data Dependence Engineering Enhancers Environment Environmental Exposure Environmental Pollutants Epithelial Cells Experimental Designs Exposure to Faculty Food Goals Health Hela Cells Human Hypersensitivity Immune Immune response In Vitro Industrialization Inflammatory Response Inhalation Lead Light Link Liquid substance Lung Measures Mechanics Mediating Medicine Methods Microscopy Modeling Molecular Mus Outcome Outcomes Research Oxidative Stress Oxides Ozone Paint Phagocytosis Pigments Plasma Play Production Proteins Proteomics Reactive Oxygen Species Regulation Research Rodent Role Sampling Serum Serum Proteins Skin Surface Testing Time Toxic effect Translating Universities Work airway epithelium base biological adaptation to stress cytokine cytotoxic design experimental study exposed human population fetal bovine serum immunoregulation in vivo innovation insight interest macrophage materials science medical schools member metal oxide nanomaterials nanoparticle oxidation ozone exposure respiratory response response to injury titanium dioxide tool transcriptome transcriptome sequencing

项目摘要

Titanium dioxide nanoparticles (TiO2 NPs) are widely used as pigments in paints, food, and cosmetics. Annual production is estimated at 1.2 M metric tons. While TiO2 NP exposure through the skin or gut is considered harmless, inhalation into the lung by workers processing these materials remains a concern. Recent results from the Payne Lab, which relocated from Georgia Tech to Duke University in January 2018, has shown that TiO2 NPs, in the absence of light, produce reactive oxygen species (ROS) that oxidize proteins in contact with the TiO2 NPs. The oxidized proteins initiate an oxidative stress response in cells. These previous experiments were carried out using blood serum proteins and HeLa and A549 cells. The goal of this R21 is to translate these experiments to the lung, working in collaboration with Dr. Robert Tighe, a faculty member in Pulmonary, Allergy, and Critical Care Medicine at Duke’s School of Medicine and an expert in the pulmonary response to environmental pollutants. Experiments will progress from bronchoalveolar lavage fluid to airway macrophage and epithelial cells. Three types of TiO2 NPs, previously characterized in the Payne Lab, will be used for experiments; industrial-grade TiO2 NPs, surface passivated TiO2 NPs that do not produce ROS, and plasma- treated TiO2 NPs with increased ROS production. The significance of this research is obtaining a molecular- level, mechanistic, understanding of the interaction of TiO2 NPs with lung cells including a comparison of rodent and human samples. The innovative aspect of this research is a new in vitro method to explore cellular responses to NPs, including toxicity. This has implications beyond TiO2 NPs as this approach could be used to understand cellular responses to a broad array of industrial and environmental NPs. Since the majority of NP studies focus on cell culture conditions that do not represent actual in vivo conditions, this experimental design is a significant technical innovation. The outcome of this research will be a mechanistic understanding of TiO2 NPs in a pulmonary environment to define their true impact on human health. While risky, extensive Payne Lab studies of these NPs in model systems, coupled with Tighe Lab expertise in the pulmonary response to environmental exposures, makes the proposed work experimentally tractable. 0

二氧化钛纳米颗粒（TiO 2 NPs）广泛用作涂料、食品和化妆品中的颜料。年度产量估计为120万公吨。虽然考虑通过皮肤或肠道暴露TiO 2 NP，加工这些材料的工人吸入肺部是无害的，这仍然是一个问题。的最新结果佩恩实验室于2018年1月从格鲁吉亚理工大学搬迁到杜克大学，该实验室表明，在没有光的情况下，NP产生活性氧物质（ROS），其氧化与NPs接触的蛋白质。 TiO 2纳米颗粒。氧化蛋白质在细胞中启动氧化应激反应。这些先前的实验是使用血清蛋白和HeLa和A549细胞进行。这个R21的目标是将这些与肺、过敏、免疫学系教员Robert Tighe博士合作，进行肺部实验，和重症监护医学在杜克医学院和专家在肺部反应，环境污染物实验将从支气管肺泡灌洗液进展到气道巨噬细胞和上皮细胞。三种类型的TiO 2纳米颗粒，先前在佩恩实验室表征，将用于实验;工业级TiO 2 NP、不产生ROS的表面钝化的TiO 2 NP和等离子体- 经处理的TiO 2 NP具有增加的ROS产生。这项研究的意义在于获得一个分子- 了解TiO 2纳米颗粒与肺细胞的相互作用，包括啮齿动物的比较和人体样本这项研究的创新之处在于，它是一种新的体外方法，对NP的反应，包括毒性。这具有超出TiO 2 NPs的影响，因为这种方法可以用于了解细胞对各种工业和环境纳米粒子的反应。由于大多数NP 研究集中于不代表实际体内条件的细胞培养条件，该实验设计是一项重大的技术创新。这项研究的结果将是一个机械的理解二氧化钛肺环境中的纳米粒子，以确定其对人类健康的真正影响。虽然风险很大，但佩恩实验室这些NP在模型系统中的研究，加上Tighe Lab在肺反应方面的专业知识，环境暴露，使得所提出的工作在实验上易于处理。 0