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：
10205073
负责人：
CHRISTINE K PAYNE
金额：
$ 20.13万
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 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10205073
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 fine particles 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

二氧化钛纳米粒子（TiO2 NPs）广泛用作油漆、食品和化妆品中的颜料。产量估计为 120 万公吨，同时考虑通过皮肤或肠道接触 TiO2 NP。加工这些材料的工人吸入肺部无害，但最近的研究结果仍然令人担忧。 Payne 实验室于 2018 年 1 月从佐治亚理工学院迁至杜克大学，结果表明 TiO2 纳米颗粒在没有光的情况下会产生活性氧（ROS），氧化与纳米颗粒接触的蛋白质氧化的蛋白质在细胞中引发氧化应激反应。使用血清蛋白以及 HeLa 和 A549 细胞进行该 R21 的目标是翻译这些。与肺科、过敏科教员 Robert Tighe 博士合作进行肺部实验，杜克大学医学院的重症监护医学和重症监护医学专家，也是肺部反应方面的专家实验将从支气管肺泡灌洗液进展到气道巨噬细胞。 Payne 实验室先前表征的三种类型的 TiO2 NP 将用于实验；工业级TiO2 NP、不产生ROS的表面钝化TiO2 NP和等离子体- 具有增加的 ROS 产量的 TiO2 纳米颗粒本研究的意义在于获得了分子- TiO2 NPs 与肺细胞相互作用的水平、机制、理解，包括啮齿动物的比较这项研究的创新之处是探索细胞的新体外方法。对 NP 的反应，包括毒性，这具有超出 TiO2 NP 范围的影响，因为这种方法可用于了解细胞对各种工业和环境纳米粒子的反应，因为大多数纳米粒子。研究重点是细胞培养条件，并不代表实际的体内条件，该实验设计这项研究的成果将是对 TiO2 的机械理解。肺部环境中的纳米颗粒确定其对人类健康的真正影响虽然存在风险，但佩恩实验室的范围广泛。在模型系统中对这些 NP 进行研究，并结合 Tighe 实验室在肺部反应方面的专业知识环境暴露，使得拟议的工作在实验上易于处理。 0

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Interaction of TiO2 nanoparticles with lung fluid proteins and the resulting macrophage inflammatory response.

TiO2 纳米颗粒与肺液蛋白的相互作用以及由此产生的巨噬细胞炎症反应。

DOI：
发表时间：
2023-09-01
期刊：
影响因子：
0
作者：
Poulsen, Karsten M;Albright, Michaela C;Niemuth, Nicholas J;Tighe, Robert M;Payne, Christine K
通讯作者：
Payne, Christine K