Accelerating Inflammation Resolution to CounterACT Chemical Injury

加速炎症消退以对抗化学损伤

基本信息

  • 批准号:
    8900466
  • 负责人:
  • 金额:
    $ 22.08万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-09-19 至 2015-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Exposures to chemical threat agents oftentimes induce strong inflammatory tissue responses that contribute to morbidity and prevent tissue repair and recovery. Pulmonary exposures to chlorine trigger a potent inflammatory response resulting in vascular leakage, cardiopulmonary depression, neutrophil infiltration and a pulmonary and systemic hypercytokinemia comparable to the cytokine storm observed in sepsis. Similar inflammatory responses are observed after inhalation exposures to phosgene and acidic (HCl) or alkaline gases (ammonia) and reactive industrial chemicals such as acrolein, and to riot control agents (CS, CN or CR), and following cutaneous exposures to vesicants. Classical anti-inflammatory treatments against chemical injury have focused on interference with target pathways involved in the initiation and maintenance of inflammation. These strategies have only been partially successful, due to the large variety of pathways and pathologies involved. The inflammatory response is divided into three temporal phases, initiation, amplification and maintenance, and resolution. A new area of inflammation research has focused on the process of inflammation resolution, an active mechanism involving the activation of signaling pathways during inflammation initiation, and the later generation of omega 3 fatty-acid derived inflammation-resolving mediators that activate resolution mechanisms. In our preliminary studies we observe that post exposure treatment with Resolvin D1, an inflammation-resolving agent, strongly inhibited skin edema formation and inflammation in mice exposed to the vesicant, CEES, and the electrophilic riot control agent, CS. Our proposed studies are designed to 1: Examine the effects of inflammation-resolving agents in mouse models of cutaneous exposures to vesicants and electrophilic chemical threats and, 2: Study the effects of inflammation-resolving agents on pulmonary injury progression in mice exposed to chlorine and HCl.
描述(由申请人提供):暴露于化学威胁剂通常会诱导强烈的炎症组织反应,导致发病并阻止组织修复和恢复。肺暴露于氯触发了一个强大的炎症反应,导致血管渗漏,心肺抑制,中性粒细胞浸润和肺和全身高细胞因子血症相媲美的细胞因子风暴中观察到的败血症。在吸入暴露于光气和酸性(HCl)或碱性气体(氨)和反应性工业化学品(如丙烯醛)以及防暴剂(CS、CN或CR)后,以及皮肤暴露于起泡剂后,观察到类似的炎症反应。针对化学损伤的经典抗炎治疗集中于干扰参与炎症的起始和维持的靶向途径。这些策略只取得了部分成功,因为涉及的途径和病理种类繁多。炎症反应分为三个时间阶段,启动,放大和维持,和解决。炎症研究的一个新领域集中在炎症消退的过程,一种涉及炎症起始期间信号通路激活的主动机制,以及激活消退机制的ω 3脂肪酸衍生的炎症消退介质的后期产生。在我们的初步研究中,我们观察到,暴露后用Resolvin D1(一种炎症消退剂)治疗,强烈抑制了暴露于发泡剂CEES和亲电子防暴剂CS的小鼠的皮肤水肿形成和炎症。我们拟定的研究旨在1:检查炎症消退剂在皮肤暴露于水疱剂和亲电化学威胁的小鼠模型中的作用,2:研究炎症消退剂对暴露于氯和HCl的小鼠肺损伤进展的影响。

项目成果

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SVEN-ERIC JORDT其他文献

SVEN-ERIC JORDT的其他文献

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{{ truncateString('SVEN-ERIC JORDT', 18)}}的其他基金

Nicotine Pouches: Chemical Composition, Toxicity and Behavioral Effects of a New Tobacco Product Category
尼古丁袋:新型烟草产品类别的化学成分、毒性和行为影响
  • 批准号:
    10673370
  • 财政年份:
    2022
  • 资助金额:
    $ 22.08万
  • 项目类别:
Molecular Core
分子核心
  • 批准号:
    9703532
  • 财政年份:
    2020
  • 资助金额:
    $ 22.08万
  • 项目类别:
Anesthetic and synthetic cooling flavors in E-cigarettes: Chemistry and respiratory effects modulating nicotine intake
电子烟中的麻醉剂和合成清凉香料:调节尼古丁摄入量的化学和呼吸效应
  • 批准号:
    9982329
  • 财政年份:
    2018
  • 资助金额:
    $ 22.08万
  • 项目类别:
Mechanisms of Itch in Poison Ivy-Induced Allergic Contact Dermatitis
毒藤引起的过敏性接触性皮炎的瘙痒机制
  • 批准号:
    9164682
  • 财政年份:
    2016
  • 资助金额:
    $ 22.08万
  • 项目类别:
Accelerating Inflammation Resolution to CounterACT Chemical Injury
加速炎症消退以对抗化学损伤
  • 批准号:
    8416589
  • 财政年份:
    2012
  • 资助金额:
    $ 22.08万
  • 项目类别:
Accelerating Inflammation Resolution to CounterACT Chemical Injury
加速炎症消退以对抗化学损伤
  • 批准号:
    8547809
  • 财政年份:
    2012
  • 资助金额:
    $ 22.08万
  • 项目类别:
Counterirritation by Menthol: Molecular Targets and Role in Airway Disease
薄荷醇的抗刺激作用:分子靶标及其在气道疾病中的作用
  • 批准号:
    8022797
  • 财政年份:
    2011
  • 资助金额:
    $ 22.08万
  • 项目类别:
Counter-Irritation by Menthol: Molecular Targets and Role in Airway Disease
薄荷醇抗刺激:分子靶标及其在气道疾病中的作用
  • 批准号:
    8209236
  • 财政年份:
    2011
  • 资助金额:
    $ 22.08万
  • 项目类别:
Counter-Irritation by Menthol: Molecular Targets and Role in Airway Disease
薄荷醇抗刺激:分子靶标及其在气道疾病中的作用
  • 批准号:
    8605272
  • 财政年份:
    2011
  • 资助金额:
    $ 22.08万
  • 项目类别:
Counter-irritation by Menthol: Molecular Targets and Role in Airway Disease
薄荷醇的抗刺激作用:分子靶标及其在气道疾病中的作用
  • 批准号:
    8431661
  • 财政年份:
    2011
  • 资助金额:
    $ 22.08万
  • 项目类别:

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