Nicotinic acid inhibits NLRP3 inflammasome activation via SIRT1 in vascular endothelial cells.
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)-1β 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.
Department of Pharmacology, Xi'an Jiaotong University, Health Science Center, Xi'an, Shaanxi 710061, China; Taizhou Polytechnic College, Taizhou, Jiangsu 225300, China.
Yanxiang
Y
Li
School of Pharmacy, Xi'an Jiaotong University, Health Science Center, Xi'an, Shaanxi 710061, China.
Guangde
G
Yang
Department of Pharmacology, Xi'an Jiaotong University, Health Science Center, Xi'an, Shaanxi 710061, China.
Xiaofeng
X
Yang
Laboratory Animal Center, Xi'an Jiaotong University, Health Science Center, Xi'an, Shaanxi 710061, China.
Weirong
W
Wang
School of Pharmacy, Xi'an Jiaotong University, Health Science Center, Xi'an, Shaanxi 710061, China.
Jiye
J
Zhang
Department of Pharmacology, Xi'an Jiaotong University, Health Science Center, Xi'an, Shaanxi 710061, China.
Yanhao
Y
He
Department of Pharmacology, Xi'an Jiaotong University, Health Science Center, Xi'an, Shaanxi 710061, China.
Wei
W
Zhang
Department of Pharmacology, Xi'an Jiaotong University, Health Science Center, Xi'an, Shaanxi 710061, China.
Ting
T
Jing
Department of Pharmacology, Xi'an Jiaotong University, Health Science Center, Xi'an, Shaanxi 710061, China. Electronic address: linrong63@aliyun.com.
Rong
R
Lin
D000255:Adenosine Triphosphate; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D020170:Caspase 1 / Q000378:metabolism; D002478:Cells, Cultured; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D058847:Inflammasomes / Q000187:drug effects; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009525:Niacin / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D056564:Sirtuin 1 / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D058847:Inflammasomes; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D017382:Reactive Oxygen Species; D009525:Niacin; D000255:Adenosine Triphosphate; D020170:Caspase 1; C447939:SIRT1 protein, human; D056564:Sirtuin 1
NLRP3 inflammasome; Nicotinic acid; ROS; SIRT1