SERINE PROTEASE-LIKE ACTIVITY, BUT NOT CALCIUM-INDEPENDENT PHOSPHOLIPASE A2

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 两个细胞内NLR家族成员Nlc4和Nlrp3在caspase-1的激活和成熟的IL-1b对特定微生物刺激的反应中起着关键作用。基于化学抑制剂的使用，一些研究表明，钙非依赖性磷脂酶A2(IPLA2)参与了炎症小体的激活和IL-1b的分泌。在这里，我们使用药理学和遗传学的方法来研究iPLA2在通过NLRC4和Nlrp3炎症体诱导的caspase-1激活中的作用。溴烯醇内酯(BEL)是一种抑制剂，最初被用来支持iPLA2在炎症体激活中的作用，它不仅阻止了内毒素和ATP诱导的caspase-1处理，也阻止了依赖NLRC4炎症体的沙门氏菌感染和胞浆鞭毛蛋白。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Two intracellular NLR family members, Nlc4 and Nlrp3, play a critical role in the activation of caspase-1 and release of mature IL-1b in response to specific microbial stimuli. Based on the use of chemical inhibitors, several studies have suggested an involvement of calcium-independent phospholipase A2 (iPLA2) in inflammasome activation and IL-1b secretion. Here we use pharmacological and genetic approaches to study the role of iPLA2 in the activation of caspase-1 induced through the Nlrc4 and Nlrp3 inflammasomes. Bromoenol lactone (BEL), an inhibitor that was originally used to support a role for iPLA2 in inflammasome activation, prevented caspase-1 processing induced not only by LPS and ATP, but also by Salmonella infection and cytosolic flagellin that rely on the Nlrc4 inflammasome.