Identification and validation of uterine stimulant methylergometrine as a potential inhibitor of caspase-1 activation.
Identification and validation of uterine stimulant methylergometrine as a potential inhibitor of caspase-1 activation.
复制标题
DOI：
10.1007/s10495-017-1405-z
复制
发表时间：
2017-10
期刊：
影响因子：
--
通讯作者：
Orzáez M
中科院分区：
文献类型：
--
作者：
García-Laínez G;Sancho M;García-Bayarri V;Orzáez M
炎症小体是先天免疫系统的细胞内多蛋白复合物。在发生炎症损伤（例如感染或细胞内损伤）时，核苷酸结合寡聚化结构域样受体 (NLR) 传感器蛋白和衔接蛋白 ASC（含有 caspase 激活和募集结构域的凋亡相关斑点样蛋白）被组装以激活蛋白酶 procaspase-1。这种蛋白酶处理 IL-1β 前体和 IL-18 细胞因子前体，这些细胞因子被释放以诱导炎症反应。炎症小体的失调会导致多种疾病的进展，例如阿尔茨海默病、糖尿病、癌症、炎症和自身免疫性疾病。我们在此描述了甲基麦角新碱 (MEM) 的鉴定，MEM 是一种目前在产后出血期间用作平滑肌收缩剂的药物，在 ASC 介导的 procaspase-1 激活筛选中作为炎性体复合物的抑制剂。在不同的促炎刺激下，MEM 可抑制细胞模型中核苷酸结合寡聚化结构域样受体蛋白 1 (NLRP1) 和核苷酸结合寡聚化结构域样受体蛋白 3 (NLRP3) 炎症小体的激活。我们的结果表明，凭借已确定的安全性和临床数据的优势，MEM 有潜力在炎症性疾病的治疗中重新定位。本文的在线版本 (doi:10.1007/s10495-017-1405-z) 包含补充材料，可供授权用户使用。
Inflammasomes are intracellular multiprotein complexes of the innate immune system. Upon an inflammatory insult, such as infection or intracellular damage, a nucleotide-binding oligomerization domain-like receptor (NLR) sensor protein and the adaptor protein ASC (apoptosis-associated speck-like protein containing a caspase activation and recruitment domain) are assembled to activate protease procaspase-1. This protease processes pro-IL-1β and pro-IL-18 cytokines, which are released to induce the inflammatory response. De-regulation of inflammasome contributes to the progression of several diseases, such as Alzheimer’s disease, diabetes, cancer, inflammatory and autoimmune disorders. We herein describe the identification of methylergometrine (MEM), a drug currently used as a smooth muscle constrictor during postpartum hemorrhage, as an inhibitor of the inflammasome complex in ASC-mediated procaspase-1 activation screening. MEM inhibits the activation of the nucleotide-binding oligomerization domain-like receptor protein 1 (NLRP1) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasomes in cellular models upon different pro-inflammatory stimuli. Our results suggest that MEM has the potential to reposition in the treatment of inflammatory diseases with the advantages of established safety and clinical data. The online version of this article (doi:10.1007/s10495-017-1405-z) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
4.6
作者：
Guo B;Fu S;Zhang J;Liu B;Li Z
通讯作者：
Li Z
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
7.8
作者：
Dinarello CA;van der Meer JW
通讯作者：
van der Meer JW
影响因子：
120.1
作者：
Hoffman, Hal M.;Yasothan, Uma;Kirkpatrick, Peter
通讯作者：
Kirkpatrick, Peter