The role of galectin-8 in the regulation of corneal infection and inflammation

Galectin-8在调节角膜感染和炎症中的作用

基本信息

  • 批准号:
    9788094
  • 负责人:
  • 金额:
    $ 41.25万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-09-30 至 2022-06-30
  • 项目状态:
    已结题

项目摘要

Project Summary The bacterium Pseudomonas aeruginosa (PA) is a leading cause of microbial infection of the cornea. One of the serious consequences of PA corneal infection is blindness resulting from persistent corneal inflammation. Approximately 30,000 cases of microbial keratitis occur annually in the United States. The innate immune system is the first line of defense against pathogens and is initiated by pattern recognition receptors which respond to invading microbes. It is known that IL-1β plays an important role in the induction of immune response in PA keratitis. In the classical immune response to bacterial infection, generation of mature IL-1β is a two-step process. The first step is the induction of pro-IL-1β expression, which is generally achieved by TLR-mediated activation of NF-B pathway that results in the induction of pro-IL-1β. A second signal then triggers the assembly of inflammasomes leading to the cleavage of caspase-1. Active (cleaved) caspase-1 cleaves pro-IL-1β to generate active IL-1β, which is secreted from the cell to mediate downstream inflammatory effects that clear the infection. Recently, we have made an exciting observation that galectin-8 knockout (Gal-8 KO) mice are resistant to PA infection. Additional pilot studies revealed that Gal-8 has the potential to regulate the activation of both TLR and inflammasome pathways. The goal of this project is to characterize the role of Gal-8 in the regulation of PA-induced immunopathology, and to develop effective strategies for prevention and regression of uncontrolled inflammatory response that results in extensive damage to the cornea and visual impairment. In Aim 1, in an effort to understand the mechanisms that render Gal-8 KO mice resistant to PA keratitis, we will test the hypothesis that Gal-8 has the capacity to dampen inflammasome-mediated generation of mature IL-1β to influence innate immune response. Specifically, in this Aim, using Gal-8 KO mice and Gal-8 deficient macrophages and neutrophils, we will characterize the role of Gal-8 in the regulation of the inflammasome pathway in PA keratitis. In Aim 2, we will determine whether Gal-8 influences the outcome of PA keratitis by modulating neutrophil elastase and/or TLR pathway. To better characterize the role of Gal-8 in the pathogenesis of PA keratitis, in Aim 3A, we propose to perform transcriptome and cytokine/chemokine proteome analyses of PA-infected corneas of WT and Gal-8 KO mice, and WT and Gal-8 KO macrophages and neutrophils. In Aim 3B, studies will be performed to determine whether Gal-8 can be targeted to control overactive immune response and corneal inflammation in the mouse model of PA keratitis. We expect that the proposed study will provide ground-breaking data, not only for understanding the molecular mechanism of PA keratitis, but also for the development of novel, galectin-based therapy that can treat blinding immunopathology resulting both from bacterial keratitis, as well as from other ocular disorders, such as corneal graft rejection and dry eye disease.
项目总结

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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Noorjahan Panjwani其他文献

Noorjahan Panjwani的其他文献

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{{ truncateString('Noorjahan Panjwani', 18)}}的其他基金

The role of galectin-8 in the regulation of corneal infection and inflammation
Galectin-8在调节角膜感染和炎症中的作用
  • 批准号:
    10186753
  • 财政年份:
    2018
  • 资助金额:
    $ 41.25万
  • 项目类别:
The Role of Selectin-Mediated Recognition in Glaucoma
选择素介导的识别在青光眼中的作用
  • 批准号:
    6820998
  • 财政年份:
    2004
  • 资助金额:
    $ 41.25万
  • 项目类别:
The Role of Selectin-Mediated Recognition in Glaucoma
选择素介导的识别在青光眼中的作用
  • 批准号:
    6927190
  • 财政年份:
    2004
  • 资助金额:
    $ 41.25万
  • 项目类别:
The Role of Selectin-Mediated Recognition in Glaucoma
选择素介导的识别在青光眼中的作用
  • 批准号:
    7087798
  • 财政年份:
    2004
  • 资助金额:
    $ 41.25万
  • 项目类别:
Core Grant for Vision Research
视觉研究核心资助
  • 批准号:
    6732716
  • 财政年份:
    2001
  • 资助金额:
    $ 41.25万
  • 项目类别:
Core Grant for Vision Research
视觉研究核心资助
  • 批准号:
    6888107
  • 财政年份:
    2001
  • 资助金额:
    $ 41.25万
  • 项目类别:
Core Grant for Vision Research
视觉研究核心资助
  • 批准号:
    6518687
  • 财政年份:
    2001
  • 资助金额:
    $ 41.25万
  • 项目类别:
Core Grant for Vision Research
视觉研究核心资助
  • 批准号:
    6635707
  • 财政年份:
    2001
  • 资助金额:
    $ 41.25万
  • 项目类别:
PATHOGENESIS OF ACANTHAMOEBA KERATITIS
棘阿米巴角膜炎的发病机制
  • 批准号:
    2162962
  • 财政年份:
    1993
  • 资助金额:
    $ 41.25万
  • 项目类别:
PATHOGENESIS OF ACANTHAMOEBA KERATITIS
棘阿米巴角膜炎的发病机制
  • 批准号:
    6518475
  • 财政年份:
    1993
  • 资助金额:
    $ 41.25万
  • 项目类别:

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