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

丝氨酸蛋白酶样活性，但不是钙独立的磷脂酶 A2

• 批准号: 7954030
• 负责人: Edward Franchi
• 金额: $ 0.35万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954030
• 关键词: 6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one; Caspase-1; Chemicals; Computer Retrieval of Information on Scientific Projects Database; Family member; Flagellin; Funding; Genetic; Grant; Institution; Mass Spectrum Analysis; Play; Process; Research; Research Personnel; Resources; Role; Salmonella infections; Serine Protease; Source; Stimulus; United States National Institutes of Health; base; biomedical resource; human PLA2G6 protein; inhibitor/antagonist; microbial; prevent; response

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 两个细胞内NLR家族成员Nlc 4和Nlrp 3在响应特定微生物刺激的caspase-1活化和成熟IL-1b释放中起关键作用。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（iPLA 2）参与炎性小体激活和IL-1b分泌。在这里，我们使用药理学和遗传学方法来研究iPLA 2在通过Nlrc 4和Nlrp 3炎性体诱导的caspase-1活化中的作用。 溴烯醇内酯（BEL）是一种最初用于支持iPLA 2在炎性体激活中的作用的抑制剂，其阻止了不仅由LPS和ATP诱导的半胱天冬酶-1加工，而且还阻止了由沙门氏菌感染和依赖于Nlrc 4炎性体的细胞溶质鞭毛蛋白诱导的半胱天冬酶-1加工。