Compromised Resolution of Inflammation following Nanoparticle Exposure in Metabolic Syndrome

代谢综合征中纳米颗粒暴露后炎症的消退效果受损

基本信息

  • 批准号:
    10441741
  • 负责人:
  • 金额:
    $ 33.77万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-04-01 至 2027-01-31
  • 项目状态:
    未结题

项目摘要

Project Summary / Abstract Individuals with metabolic syndrome (MetS) compose a significant and growing proportion of our U.S. and global population (> 25%). It has been established that the presence of chronic diseases, such as MetS, enhances and prolongs environmental exposure-induced inflammation. Individuals with MetS have demonstrated enhanced inflammation due to ambient particulate matter exposures of which a significant proportion is nano-sized. The mechanisms associated with this enhanced susceptibility represent a significant gap in our knowledge. Mounting data from the Shannahan laboratory suggests that dysregulation of inflammatory resolution contributes to the exacerbated toxicity and disease progression observed in MetS. Specifically, nanoparticle inhalation exposures induce a pulmonary inflammatory response that is exacerbated and extended due to MetS. This inflammatory response corresponds with suppression of specialized pro-resolving mediators that facilitate inflammatory resolution. Our data suggests following inhalation, nanoparticles gain unique biocoronas on their surface that enhance the pro-inflammatory response while inhibiting resolution signaling. Further, our preliminary data demonstrates MetS disrupts ω-3 fatty acid metabolism impairing resolution. This proposal examines the hypothesis that dysregulation of inflammatory resolution following nanoparticle exposure mediates the susceptibility observed in MetS by exacerbating inflammatory responses and facilitating development and progression of chronic disease. The hypothesis will be tested through the completion of three main goals: 1) Delineation of pulmonary nanoparticle-biocorona alterations throughout metabolic syndrome development and the inflammation signaling consequences; 2) Determination of inflammatory resolution and specialized pro- resolving mediator kinetics following nanoparticle exposure in MetS and healthy mouse models; 3) Elucidation of differential ω-3 fatty acid metabolism in MetS following nanoparticle exposure. These mechanisms represent potential key regulators that are dysregulated in MetS, facilitating exacerbated responses and also are potential targets of therapeutic interventions. Typically, research and treatment strategies addressing exposure-induced inflammation focus on suppression of pro-inflammatory pathways rather than elucidation and effective stimulation of resolution processes. Completion of the project will generate new knowledge required to understand distinct mechanisms of toxicity in prevalent and sensitive subpopulations such as MetS. Elucidation of these mechanisms will allow for new disease prevention and treatment strategies while also broadening public health protections to environmental exposures.
项目摘要/摘要

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Jonathan Henry Shannahan其他文献

Jonathan Henry Shannahan的其他文献

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{{ truncateString('Jonathan Henry Shannahan', 18)}}的其他基金

Early Periodontal Health Impacts of Electronic Nicotine Delivery System (ENDS) Usage
电子尼古丁输送系统 (ENDS) 使用对早期牙周健康的影响
  • 批准号:
    10691174
  • 财政年份:
    2022
  • 资助金额:
    $ 33.77万
  • 项目类别:
Compromised Resolution of Inflammation following Nanoparticle Exposure in Metabolic Syndrome
代谢综合征中纳米颗粒暴露后炎症的消退效果受损
  • 批准号:
    10597165
  • 财政年份:
    2022
  • 资助金额:
    $ 33.77万
  • 项目类别:
African-American Susceptibility to Periodontal Disease due to Electronic Nicotine Delivery Systems (ENDS) Usage
非裔美国人因使用电子尼古丁传送系统 (ENDS) 而易患牙周病
  • 批准号:
    10453478
  • 财政年份:
    2021
  • 资助金额:
    $ 33.77万
  • 项目类别:
African-American Susceptibility to Periodontal Disease due to Electronic Nicotine Delivery Systems (ENDS) Usage
非裔美国人因使用电子尼古丁传送系统 (ENDS) 而易患牙周病
  • 批准号:
    10561750
  • 财政年份:
    2021
  • 资助金额:
    $ 33.77万
  • 项目类别:
Assessment of Cured-In-Place Pipe Installation Emissions and Toxicity
现场固化管道安装排放和毒性评估
  • 批准号:
    9808278
  • 财政年份:
    2019
  • 资助金额:
    $ 33.77万
  • 项目类别:
Disease-Induced Modification in Nanoparticle-Corona Identity and Toxicity
疾病引起的纳米颗粒电晕特性和毒性的改变
  • 批准号:
    9392983
  • 财政年份:
    2017
  • 资助金额:
    $ 33.77万
  • 项目类别:
Disease-Induced Modification in Nanoparticle-Corona Identity and Toxicity
疾病引起的纳米颗粒电晕特性和毒性的改变
  • 批准号:
    9056595
  • 财政年份:
    2015
  • 资助金额:
    $ 33.77万
  • 项目类别:

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