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.

项目总结/摘要 该项目将比较费城三个地下地铁站的室内空气质量， 对应的地上城市位置以及一个郊区位置。此前，PM 费城地铁站的辐射水平可能比城市街道高出五倍。我们将 评估来自不同位置的颗粒物（PM）对肺上皮细胞（16 HBE和原发性 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）和异生素反应元件（XRE）。主要目的是评估 各种PM组分对这些细胞反应的贡献。在目标1中，我们将收集总共102个样本 从不同的位置，并确定到什么程度的黑碳（BC），超细颗粒（UFP）， 金属与细胞效应相关。BC和UFP都与细胞氧化有关， 应力地铁PM中的铁、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分，这些都与氧化应激有关， ARE从其他PM来源激活。在目标2中，我们将研究可溶性/可螯合金属的作用， 对整个颗粒中的金属对细胞的影响，以及评估有机化合物的贡献， 这些影响。作为这项工作的一部分，我们将探讨XRE和ARE途径对细胞凋亡的贡献。 通过使用针对相关传感器/转录因子、芳烃受体（AhR）和 nrf 2，分别。剂量反应曲线将用于评估浓度范围内的效应。结果 将有助于理解和理想地减轻地铁空气颗粒物的健康风险。我们组建了一个 多学科的研究团队，包括空气颗粒分析，细胞氧化应激， 统计分析和金属分析，以及EPA的吸入毒理学家。该项目包括 10名本科生在维拉诺瓦的三个不同部门工作， 在环保局实验室工作学生将是工作的主要驱动力，它的解释，并在 国家会议和作者发表的作品。