Nicotinic acid inhibits NLRP3 inflammasome activation via SIRT1 in vascular endothelial cells
Nicotinic acid inhibits NLRP3 inflammasome activation via SIRT1 in vascular endothelial cells
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烟酸通过 SIRT1 抑制血管内皮细胞中 NLRP3 炎症小体的激活
DOI：
10.1016/j.intimp.2016.09.003
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发表时间：
2016-11-01
影响因子：
5.6
通讯作者：
Lin, Rong
中科院分区：
文献类型：
--
作者：
Li, Yanxiang;Yang, Guangde;Lin, Rong
越来越多的证据表明，NLRP3炎症小体可启动炎症反应，参与心血管疾病。烟酸(NA)具有潜在的抗炎作用。本研究旨在探讨去甲肾上腺素(NA)对NLRP3炎症小体激活的影响及其机制。研究发现，脂多糖(LPS)和三磷酸腺苷(ATP)可激活人脐静脉内皮细胞(HUVECs)NLRP3炎性小体。NA可抑制NLRP3炎性小体的激活和随后caspase-1的裂解以及IL-1β的分泌。此外，NA可上调内毒素+ATP刺激的HUVECs SIRT1的表达。重要的是，SIRT1基因的敲除逆转了NA对NLRP3炎症小体激活的抑制作用。进一步的研究表明，NA还能减少HUVECs中ROS的产生。此外，NA抑制NLRP3炎症体的激活部分是通过抑制ROS来实现的。综上所述，这些结果表明NA能够调节HUVECs中NLRP3炎症体的激活，这可能部分是通过SIRT1和ROS介导的。(C)2016爱思唯尔B.V.保留所有权利。
Emerging evidences indicated that NLRP3 inflammasome initiates inflammatory response involved in cardiovascular disease. Nicotinic acid (NA) has been known to possess potential anti-inflammatory property. The aim of this study was to investigate the effect of NA on the activation of NLRP3 inflammasome and the underlying mechanisms. It was found that lipopolysaccharide (LPS) and adenosine triphosphate (ATP) triggered the activation of NLRP3 inflammasome in human umbilical vein endothelial cells (HUVECs). NA inhibited NLRP3 inflammasome activation and subsequent caspase-1 cleavage as well as interleukin (IL)-1 beta secretion. Moreover, NA administration up-regulated SIRT1 expression in HUVECs stimulated with LPS plus ATP. Importantly, knockdown of SIRT1 reversed the inhibitory effect of NA on the activation of NLRP3 inflammasome. Further study revealed that NA also decreased the generation of reactive oxygen species (ROS) in HUVECs. In addition, NA inhibited NLRP3 inflammasome activation partly through suppression of ROS. Taken together, these findings indicate that NA is able to regulate the activation of NLRP3 inflammasome in HUVECs, which may be partly mediated by SIRT1 and ROS. (C) 2016 Elsevier B.V. All rights reserved.