Tissue specific detection of inflammation in vivo.

摘要 炎症的发展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，在细菌感染中，宿主的炎症反应也会促进病原体清除。 如炎症性疾病，如结肠炎，其中慢性炎症反应导致局部发病 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 炎症是炎症体，是一种多蛋白复合体，导致caspase-1和 裂解和释放炎症介质，如IL-1β。监测细胞炎症反应的方法 体内，我们已经开发出caspase-1生物传感器，允许检测炎症反应在 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。这个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，以及开发 一种动物模型，将是监测组织特异性炎症反应的有价值的工具 人类疾病的无数小鼠模型。

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.