Mesenchymal inflammatory signaling in regulation of the immune response and tissue dysfunction during lipopolysaccharide-induced acute lung injury

间充质炎症信号在脂多糖诱导的急性肺损伤期间调节免疫反应和组织功能障碍

基本信息

项目摘要

PROJECT SUMMARY/ABSTRACT Acute respiratory distress syndrome (ARDS) is a type of respiratory failure characterized by severe pulmonary inflammation leading to alveolar injury, non-cardiogenic pulmonary edema, and impaired gas exchange often necessitating mechanical ventilation. ARDS can be caused by direct or indirect injury to the lungs, with the most common etiologies of injury being pneumonia, aspiration of gastric contents and sepsis. Despite significant interest in finding new therapies for ARDS, treatment has remained predominately supportive, highlighting the need for improved mechanistic understanding. The pulmonary mesenchyme resides in close proximity to the alveolar epithelium, vascular endothelium, and resident and recruited immune cells, placing the mesenchyme in an optimal position to synthesize and respond to signals from the microenvironment. In this proposal we aim to elucidate how the pulmonary mesenchyme incorporates inflammatory signals to modify the immune response and tissue injury in ARDS. The nuclear factor -B (NF-B) family of transcription factors are activated downstream of several pattern-recognition and cytokine receptors, and play an important role in mediating inflammatory responses. A20, encoded by Tnfaip3, is a negative regulator of NF-B, and has been found in both immune and epithelial cells to play a crucial role in limiting excessive inflammation and tissue injury. The intranasal delivery of bacterial lipopolysaccharide (LPS) is a well-accepted murine model for ARDS, and LPS is known to activate NF-B through the pattern-recognition receptor Toll-like receptor 4 (TLR4). Preliminary data from our lab shows that in response to LPS, lung fibroblasts in which Tnfaip3 has been deleted have increased expression of both chemokines and cytokines known to recruit immune cells and alter vascular permeability, both physiologically important aspects of ARDS pathogenesis. We hypothesize that impaired negative regulation of mesenchymal NF-B signaling in ARDS leads to increased pulmonary recruitment of immune cells and physiologic injury, and propose experiments to test this hypothesis. Answering these questions will lead to important insight into the role of the lung mesenchyme in mediating the pathophysiology of ARDS. We hope that the fundamental knowledge gained with these studies will eventually contribute to the development of more targeted therapeutics for this devastating disease. The above experimental proposal is part of a comprehensive training plan that I have built with my mentors to develop the skills and knowledge needed to become a successful independent investigator in the field of lung biology, with an emphasis on acute lung injury/ARDS. As a unique part of this plan I have assembled a Career Development Committee composed of physician-scientists from the fields of pulmonology and immunology who will serve as both scientific and career advisors. Upon completion of the proposed training plan with the support of my mentors, advisors, and within the strong research environment that UCSF provides, I will be well-positioned to make both a meaningful contribution to the understanding of ARDS and meet my training goals.
项目总结/文摘

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)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Nancy Christine Allen其他文献

Nancy Christine Allen的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Nancy Christine Allen', 18)}}的其他基金

Role of stromal inflammatory signaling in the aging of lung resident lymphocytes
基质炎症信号在肺驻留淋巴细胞衰老中的作用
  • 批准号:
    10723431
  • 财政年份:
    2023
  • 资助金额:
    $ 7.51万
  • 项目类别:
Mesenchymal inflammatory signaling in regulation of the immune response and tissue dysfunction during lipopolysaccharide-induced acute lung injury
间充质炎症信号在脂多糖诱导的急性肺损伤期间调节免疫反应和组织功能障碍
  • 批准号:
    10806558
  • 财政年份:
    2022
  • 资助金额:
    $ 7.51万
  • 项目类别:

相似海外基金

Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome
急性肺损伤和急性呼吸窘迫综合征的治疗
  • 批准号:
    8429041
  • 财政年份:
    2011
  • 资助金额:
    $ 7.51万
  • 项目类别:
Analysis of extravascular lung water dynamics and exhaustive evaluation of pulmonary epithelial metabolites to establish a novel therapeutic approach for acute lung injury/ acute respiratory distress syndrome
分析血管外肺水动力学和详尽评估肺上皮代谢物,以建立急性肺损伤/急性呼吸窘迫综合征的新治疗方法
  • 批准号:
    22592023
  • 财政年份:
    2010
  • 资助金额:
    $ 7.51万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
OBSERVATIONAL STUDY OF ACUTE LUNG INJURY & ACUTE RESPIRATORY DISTRESS SYNDROME
急性肺损伤的观察性研究
  • 批准号:
    7603766
  • 财政年份:
    2007
  • 资助金额:
    $ 7.51万
  • 项目类别:
Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome
急性肺损伤和急性呼吸窘迫综合征的治疗
  • 批准号:
    8602427
  • 财政年份:
    2005
  • 资助金额:
    $ 7.51万
  • 项目类别:
Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome
急性肺损伤和急性呼吸窘迫综合征的治疗
  • 批准号:
    8602351
  • 财政年份:
    2005
  • 资助金额:
    $ 7.51万
  • 项目类别:
Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome
急性肺损伤和急性呼吸窘迫综合征的治疗
  • 批准号:
    8654999
  • 财政年份:
    2005
  • 资助金额:
    $ 7.51万
  • 项目类别:
Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome
急性肺损伤和急性呼吸窘迫综合征的治疗
  • 批准号:
    8844846
  • 财政年份:
    2005
  • 资助金额:
    $ 7.51万
  • 项目类别:
Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome
急性肺损伤和急性呼吸窘迫综合征的治疗
  • 批准号:
    8328484
  • 财政年份:
    2005
  • 资助金额:
    $ 7.51万
  • 项目类别:
Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome
急性肺损伤和急性呼吸窘迫综合征的治疗
  • 批准号:
    8328493
  • 财政年份:
    2005
  • 资助金额:
    $ 7.51万
  • 项目类别:
Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome
急性肺损伤和急性呼吸窘迫综合征的治疗
  • 批准号:
    8020428
  • 财政年份:
    2005
  • 资助金额:
    $ 7.51万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了