Air pollution disrupts Inflammasome Regulation in HEart And Lung Total Health (AIRHEALTH)

空气污染扰乱心肺总体健康中的炎症小体调节 (AIRHEALTH)

基本信息

  • 批准号:
    10460326
  • 负责人:
  • 金额:
    $ 212万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-08-01 至 2023-01-13
  • 项目状态:
    已结题

项目摘要

ABSTRACT: OVERALL COMPONENT Exposure to air pollution from automobile exhaust and forest fires is a significant, rapidly growing global public health burden that contributes to cardiopulmonary pathogenesis. Produced by epithelial and inflammatory cells, interleukin-1 beta (IL-1β) is key to this inflammatory response within blood, lung, cardiac, and vascular tissues, and primarily associated with acute and chronic inflammation upon exposure to pollutants. Accordingly, understanding the mechanisms of the IL-1β and other pathways will significantly benefit cardiopulmonary health since therapies are available to block this pathway and since knowledge of direct mechanisms of how air pollution leads to cardiopulmonary diseases is needed to shape policy in public health. Our central objective is to test distinct but intertwined mechanistic aspects of IL-1β and other pathway regulation in inflammation-associated cardiopulmonary pathology linked to air pollution. We will test the hypothesis that the immunopathology of cardiovascular and pulmonary diseases are linked to IL-1β and/or other pathways, as we have preliminary data demonstrating activation of IL-1β and inflammasome, and other pathways in air pollution exposure, particularly PM2.5. We understand there are other pathways other than IL-1β involved and to this end, we have proposed unbiased, agnostic experiments in all projects and cores, especially the systems biology approach of project 2. Furthermore, our data show the link of immune pathways to clinical outcomes, such as increase systolic blood pressure, in young children and adolescents exposed to air pollution. We have created synergy and dependency of all the projects and cores since we use all the same samples from the same cohorts, we share data to be able to create composite biological biomarkers to link pathology to disease (i.e. asthma or increased blood pressure). As an example of our innovation together, we have proposed using induced pluripotent stem cells (iPSCs) in both lung and heart models (Projects 1 and 3) to screen and identify agents that block IL-1β and other pathway effects. Our aims are: 1. Describe the mechanisms underlying heart, lung, and immune diseases associated with air pollution (PM2.5) exposure. We will identify and characterize biomarkers of acute and chronic environmental exposure to air pollution that predict cardiopulmonary diseases. 2. Ensure the efforts of the three scientific projects and project cores will be synergistic, coordinated, and integrated. We describe specifically how the three projects and cores are synergistic and how we will integrate our study findings with other efforts to investigate IL-1β and other pathways. 3: Provide a highly interactive, collaborative, and multi-disciplinary team of investigators and resources to support our goals. We describe our multi-disciplinary facilities and investigators that will contribute to the overall success of the PPG, called AIRHEALTH. If our program and overall aims are met, we will define the mechanistic links of lung and heart diseases with IL-1β and other pathways, which will likely lead to clinical app. of biologicals and other drugs in individuals exposed to acute and/or chronic air pollution.
摘要:暴露于汽车尾气和森林火灾造成的空气污染是 导致心肺发病机制的重大、快速增长的全球公共卫生负担。 由上皮细胞和炎症细胞产生的白细胞介素-1 β(IL-1β)是这种炎症反应的关键 在血液、肺、心脏和血管组织中,主要与急性和慢性炎症相关 暴露在污染物中。因此,了解IL-1β和其他途径的机制将有助于 显著有益于心肺健康,因为治疗可用于阻断该途径, 需要了解空气污染如何导致心肺疾病的直接机制, 公共卫生政策。我们的中心目标是测试IL-1β和IL-10的不同但相互交织的机制方面, 与空气污染相关的炎症相关心肺病理学中的其他途径调节。我们将 检验心血管和肺部疾病的免疫病理学与IL-1β相关的假设 和/或其他途径,因为我们有初步数据表明IL-1β和炎性小体的激活, 空气污染暴露的其他途径,特别是PM2.5。我们知道还有其他途径 IL-1β参与,为此,我们在所有项目和核心中提出了无偏倚的不可知实验, 特别是项目2的系统生物学方法。此外,我们的数据显示, 暴露于空气中的幼儿和青少年的临床结果,如收缩压升高 污染我们已经创建了所有项目和核心的协同作用和依赖关系,因为我们使用所有相同的 来自相同队列的样本,我们共享数据,以便能够创建复合生物标志物, 病理学疾病(即哮喘或血压升高)。作为我们共同创新的一个例子, 已经提出在肺和心脏模型中使用诱导多能干细胞(iPSC)(项目1和3) 筛选和鉴定阻断IL-1β和其他途径作用的药物。我们的目标是:1.描述 与空气污染(PM2.5)暴露相关的心脏,肺和免疫疾病的潜在机制。 我们将确定和表征急性和慢性环境暴露于空气污染的生物标志物, 预测心肺疾病。2.确保三大科学工程和项目核心的努力 将是协同的,协调的,综合的。我们具体描述了这三个项目和核心 是协同作用的,以及我们将如何将我们的研究结果与其他研究IL-1β和其他 途径。3:提供一个高度互动、协作和多学科的调查人员团队, 支持我们的目标。我们描述了我们的多学科设施和调查人员, 有助于PPG的整体成功,称为空气健康。如果我们的计划和总体目标得到实现,我们 将定义肺和心脏疾病与IL-1β和其他途径的机制联系,这可能会导致 涉及生物制剂和其它药物在暴露于急性和/或慢性空气污染的个体中的临床应用。

项目成果

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Kari C. Nadeau其他文献

Baseline epitope-specific IgE profiles are predictive of sustained unresponsiveness or high threshold 1-year post oral immunotherapy in the POISED trial
在“口服免疫治疗疗效和安全性评估(POISED)”试验中,基线表位特异性免疫球蛋白E(IgE)谱可预测口服免疫治疗1年后持续无反应或高阈值反应情况。
  • DOI:
    10.1016/j.jaci.2024.10.017
  • 发表时间:
    2025-03-01
  • 期刊:
  • 影响因子:
    11.200
  • 作者:
    Maria Suprun;Ashley Sang Eun Lee;Robert Getts;Simon Peck;Sayantani B. Sindher;Kari C. Nadeau;R. Sharon Chinthrajah;Stephen J. Galli;Hugh A. Sampson
  • 通讯作者:
    Hugh A. Sampson
Identification , Characterization , and initial epitope mapping of a pine nut allergen
松子过敏原的鉴定、表征和初始表位作图
  • DOI:
  • 发表时间:
    2016
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Yuzhu Zhang;Wen;Yuting Fan;Jiang Yi;S. Lyu;Kari C. Nadeau;Tara H. McHugh
  • 通讯作者:
    Tara H. McHugh
Novel dosing strategy of omalizumab during multi-allergen oral-immunotherapy
  • DOI:
    10.1016/j.waojou.2020.100415
  • 发表时间:
    2020-08-01
  • 期刊:
  • 影响因子:
  • 作者:
    Sayantani B. Sindher;Andrew Long;Natasha Purington;Divya Kumar;Stacey Skura;Margaret A. Woch;Tiffany Tan;Andres Alvarez;R. Sharon Chinthrajah;Maria Garcia-Lloret;Kari C. Nadeau
  • 通讯作者:
    Kari C. Nadeau
How does global warming contribute to disorders originating from an impaired epithelial barrier?
全球变暖如何导致源自上皮屏障受损的疾病?
  • DOI:
    10.1016/j.anai.2023.08.010
  • 发表时间:
    2023-12-01
  • 期刊:
  • 影响因子:
    4.700
  • 作者:
    Cevdet Ozdemir;Umut Can Kucuksezer;Ismail Ogulur;Yagiz Pat;Duygu Yazici;Ioana Agache;Marek Jutel;Kari C. Nadeau;Mübeccel Akdis;Cezmi A. Akdis
  • 通讯作者:
    Cezmi A. Akdis
Decreased Migratory Potential of Treg Cells in CRSwNP
  • DOI:
    10.1016/j.otohns.2010.06.707
  • 发表时间:
    2010-08-01
  • 期刊:
  • 影响因子:
  • 作者:
    Amanda Munoz;Kari C. Nadeau;Peter H. Hwang
  • 通讯作者:
    Peter H. Hwang

Kari C. Nadeau的其他文献

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{{ truncateString('Kari C. Nadeau', 18)}}的其他基金

Clinical Core
临床核心
  • 批准号:
    10584556
  • 财政年份:
    2022
  • 资助金额:
    $ 212万
  • 项目类别:
Clinical Core
临床核心
  • 批准号:
    10419277
  • 财政年份:
    2022
  • 资助金额:
    $ 212万
  • 项目类别:
Administrative Core for the Air pollution disrupts Inflammasome Regulation in HEart And Lung Total Health (AIRHEALTH) Study
空气污染的管理核心扰乱心肺总体健康(AIRHEALTH)研究中的炎症小体调节
  • 批准号:
    10269331
  • 财政年份:
    2021
  • 资助金额:
    $ 212万
  • 项目类别:
Clinical Core
临床核心
  • 批准号:
    10491675
  • 财政年份:
    2021
  • 资助金额:
    $ 212万
  • 项目类别:
Clinical Core
临床核心
  • 批准号:
    10687221
  • 财政年份:
    2021
  • 资助金额:
    $ 212万
  • 项目类别:
Administrative Core for the Air pollution disrupts Inflammasome Regulation in HEart And Lung Total Health (AIRHEALTH) Study
空气污染的管理核心扰乱心肺总体健康(AIRHEALTH)研究中的炎症小体调节
  • 批准号:
    10684157
  • 财政年份:
    2021
  • 资助金额:
    $ 212万
  • 项目类别:
Air pollution disrupts Inflammasome Regulation in HEart And Lung Total Health (AIRHEALTH)
空气污染扰乱心肺总体健康中的炎症小体调节 (AIRHEALTH)
  • 批准号:
    10684155
  • 财政年份:
    2021
  • 资助金额:
    $ 212万
  • 项目类别:
Interaction between genetic, lifestyle and environmental factors determining circulating angiotensin-converting enzyme 2 protein expression: implications for the severity of COVID-19 infection
遗传、生活方式和环境因素之间的相互作用决定循环血管紧张素转换酶 2 蛋白表达:对 COVID-19 感染严重程度的影响
  • 批准号:
    10228516
  • 财政年份:
    2021
  • 资助金额:
    $ 212万
  • 项目类别:
Project 1 for the Air pollution disrupts Inflammasome Regulation in HEart And Lung Total Health (AIRHEALTH) Study
空气污染扰乱心肺总体健康 (AIRHEALTH) 研究中的炎症小体调节项目 1
  • 批准号:
    10684167
  • 财政年份:
    2021
  • 资助金额:
    $ 212万
  • 项目类别:
Project 1 for the Air pollution disrupts Inflammasome Regulation in HEart And Lung Total Health (AIRHEALTH) Study
空气污染扰乱心肺总体健康 (AIRHEALTH) 研究中的炎症小体调节项目 1
  • 批准号:
    10269334
  • 财政年份:
    2021
  • 资助金额:
    $ 212万
  • 项目类别:

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  • 批准号:
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