Cellular effects of subway air particles in human lung cells

地铁空气颗粒对人体肺细胞的影响

• 批准号: 10360016
• 负责人: Kabindra Man Shakya
• 金额: $ 34.67万
• 依托单位: VILLANOVA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10360016
• 关键词: Address; Air; Antimony; Antioxidants; Aromatic Polycyclic Hydrocarbons; Aryl Hydrocarbon Receptor; Asian; Binding; Caliber; Carbon Black; Cells; Chronic Disease; Cities; Copper; Cytochrome P450; Defense Mechanisms; Dose; Enzymes; Epithelial Cells; European; Exposure to; Faculty; Generations; Goals; Health; Human; Hydrogen Peroxide; Indoor Air Quality; Inflammation; Inflammatory; Inhalation; Interleukin-6; Investigation; Iron; Knowledge; Lead; Location; Lung; Mediator of activation protein; Metals; Oxidative Stress; Oxides; Particle Size; Particulate; Particulate Matter; Pathway interactions; Philadelphia; Positioning Attribute; Proteins; Publishing; Pulmonary Heart Disease; Reactive Oxygen Species; Research; Research Personnel; Response Elements; Risk; Role; Sampling; Site; Small Interfering RNA; Source; Statistical Data Interpretation; Stress; Students; Subway; Suspensions; System; Time; Toxic effect; Trace metal; Training; Ultrafine; Universities; Work; Xenobiotics; Zinc; adverse birth outcomes; aqueous; bronchial epithelium; coarse particles; cytokine; cytotoxicity; fine particles; inflammatory marker; insight; metal chelator; metallicity; multidisciplinary; nervous system disorder; particle; remediation; response; sensor; suburb; symposium; transcription factor; ultrafine particle; undergraduate student; urban area

PROJECT SUMMARY/ABSTRACT This project will compare indoor air quality at three underground subway stations in Philadelphia with the corresponding aboveground urban locations as well as one suburban location. We found previously that PM levels in Philadelphia subway stations can be up to five times higher than levels on an urban street. We will assess effects of particulate matter (PM) from the various locations on lung epithelial cells (16HBE and primary cells), assessing cytotoxicity, oxidative stress, and the cellular response pathways involving the antioxidant response element (ARE) and the xenobiotic response element (XRE). A primary purpose is to assess the contributions of various PM components to these cellular responses. In Aim 1, we will collect 102 total samples from the various locations and determine to what extent levels of black carbon (BC), ultrafine particles (UFP), and metals correlate with the cellular effects. Both BC and UFP have been associated with cellular oxidative stress. Subway PM is particularly high in metals such as iron, copper, antimony and zinc, which come from the rails, wheels, brake pads, and other parts of the trains, which have been correlated with oxidative stress and ARE activation from other PM sources. In Aim 2, we will examine the role of soluble/chelatable metals compared to metals in whole particles on the cellular effects, as well assess contributions from organic compounds on these effects. As part of this work, we will probe the contributions of the XRE and ARE pathways to the cellular effects by using siRNA against the relevant sensors/transcription factors, aryl hydrocarbon receptor (AhR) and Nrf2, respectively. Dose response curves will be used to assess effects over a range of concentrations. Results will help in understanding and ideally mitigating the health risks of subway air particles. We have assembled a multidisciplinary team of researchers, including experts in air particulate analysis, cellular oxidative stress, statistical analysis, and analytical metal analysis, and an inhalation toxicologist at the EPA. The project includes ten undergraduate student positions working in three different departments at Villanova and two summer positions at an EPA lab. Students will be primary drivers of the work, its interpretation, and presentation at national conferences and authors on published work.

项目概要/摘要 该项目将比较费城三个地铁站的室内空气质量与 相应的地上城市位置以及一个郊区位置。我们之前发现 PM 费城地铁站的水位最高可达城市街道水位的五倍。我们将 评估不同位置的颗粒物 (PM) 对肺上皮细胞（16HBE 和原代细胞）的影响 细胞），评估细胞毒性、氧化应激和涉及抗氧化剂的细胞反应途径 反应元件（ARE）和外源反应元件（XRE）。主要目的是评估 各种 PM 成分对这些细胞反应的贡献。在目标 1 中，我们将总共收集 102 个样本 并确定黑碳 (BC)、超细颗粒 (UFP)、 和金属与细胞效应相关。 BC 和 UFP 均与细胞氧化有关 压力。地铁颗粒物中铁、铜、锑和锌等金属含量特别高，这些金属来自 铁轨、车轮、刹车片和火车的其他部件，这些部件与氧化应激和 来自其他 PM 源的 ARE 激活。在目标 2 中，我们将比较可溶/可螯合金属的作用 整个颗粒中的金属对细胞的影响，以及评估有机化合物对细胞影响的贡献 这些影响。作为这项工作的一部分，我们将探讨 XRE 和 ARE 途径对细胞 使用 siRNA 针对相关传感器/转录因子、芳烃受体 (AhR) 和 分别是Nrf2。剂量响应曲线将用于评估一定浓度范围内的效果。结果 将有助于了解并理想地减轻地铁空气颗粒的健康风险。我们组装了一个 多学科研究团队，包括空气颗粒分析、细胞氧化应激、 统计分析、金属分析以及美国环保署的吸入毒理学家。该项目包括 维拉诺瓦大学三个不同院系的十个本科生职位和两个暑期职位 EPA 实验室的职位。学生将成为作品及其解释和演示的主要推动者 国家会议和已发表作品的作者。