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Tissue specific detection of inflammation in vivo.

体内炎症的组织特异性检测。

基本信息

批准号：
10374847
负责人：
Edward M Campbell
金额：
$ 7.11万
依托单位：
LOYOLA UNIVERSITY CHICAGO
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：
2021-03-18 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10374847
关键词：
Animal Model Animals Autoimmune Diseases Automobile Driving Bacterial Infections Bioluminescence Biosensor C-terminal CASP1 gene CD4 Positive T Lymphocytes Cells Chronic Colitis Colon Cre lox recombination system DNA cassette Detection Development Diabetes Mellitus Disease Disease model Enterobacteria phage P1 Cre recombinase Environment Enzyme-Linked Immunosorbent Assay Enzymes Epithelial Cells Event Exhibits Generations Goals Harvest Host Defense Immune response In Vitro Infection Infectious Skin Diseases Inflammasome Inflammation Inflammation Mediators Inflammatory Inflammatory Bowel Diseases Inflammatory Response Interleukin-1 beta Intestinal Diseases Intestines Lead LoxP-flanked allele Luciferases Lung diseases Malignant Neoplasms Measures Mediating Mediator of activation protein Methods Molecular Monitor Multiprotein Complexes Mus Myeloid Cells N-terminal Neurodegenerative Disorders Pathogenesis Pathology Pattern Quantitative Reverse Transcriptase PCR Resolution Reverse Transcriptase Polymerase Chain Reaction Series Site Skin Sodium Dextran Sulfate Staphylococcus aureus Staphylococcus aureus infection Sterility Techniques Time Tissues Transgenes Transgenic Mice Translating Ulcerative Colitis Validation Western Blotting cell type cytokine dextran sulfate sodium induced colitis economic value granulocyte human disease human model in vivo intestinal epithelium macrophage monocyte mouse model novel pathogen recruit sensor subcutaneous therapeutic development tool

项目摘要

Abstract The development and resolution of inflammation is central to the pathogenesis of numerous human diseases. This is true of bacterial infections, in which host inflammatory responses promote pathogen clearance, as well as inflammatory disorders, such as colitis, in which chronic inflammatory responses drive pathogenesis in local tissue environments. In both cases, a critical mediator of cellular inflammatory responses which drive tissue inflammation is the inflammasome, a multiprotein complex, which leads to the activation of caspase-1 and the cleavage and release of inflammatory mediators, such as IL-1β. To monitor cellular inflammatory responses in vivo, we have developed caspase-1 biosensors that allow the detection of inflammatory responses in the context of mouse models of bacterial infection (S. aureus) and colitis. In this application, we propose to develop mice expressing this novel biosensor in a tissue specific fashion. This mouse model will allow us to define the cell types driving inflammation in the context of these established disease models as well as develop an animal model which will be a valuable tool to monitor tissue specific inflammatory responses in the context of numerous mouse models of human disease.

抽象的炎症的发生和消退是许多人类疾病发病机制的核心。细菌感染也是如此，宿主炎症反应也促进病原体清除作为炎症性疾病，例如结肠炎，其中慢性炎症反应驱动局部的发病机制组织环境。在这两种情况下，驱动组织的细胞炎症反应的关键介质炎症是炎症小体，一种多蛋白复合物，可导致 caspase-1 和 caspase-1 的激活炎症介质的裂解和释放，例如 IL-1β。监测细胞炎症反应在体内，我们开发了 caspase-1 生物传感器，可以检测体内炎症反应细菌感染（金黄色葡萄球菌）和结肠炎小鼠模型的背景。在本申请中，我们建议开发以组织特异性方式表达这种新型生物传感器的小鼠。该鼠标模型将使我们能够在这些已建立的疾病模型的背景下定义驱动炎症的细胞类型并开发动物模型将成为监测组织特异性炎症反应的有价值的工具许多人类疾病的小鼠模型。