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 inflammaso...

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Bibliographic Details
Published in:	International immunopharmacology 2016-11, Vol.40, p.211-218
Main Authors:	Li, Yanxiang, Yang, Guangde, Yang, Xiaofeng, Wang, Weirong, Zhang, Jiye, He, Yanhao, Zhang, Wei, Jing, Ting, Lin, Rong
Format:	Article
Language:	eng
Subjects:	Acids Activation Activation analysis Adenosine Triphosphate Anti-Inflammatory Agents - pharmacology ATP Cardiovascular disease Cardiovascular diseases Caspase Caspase 1 - metabolism Caspase-1 Cells Cells, Cultured Endothelial cells Human Umbilical Vein Endothelial Cells - drug effects Human Umbilical Vein Endothelial Cells - metabolism Humans IL-1β Inflammasomes Inflammasomes - drug effects Inflammation Inflammatory response Inhibition Interleukin Interleukin-1beta - metabolism Lipopolysaccharides Niacin - pharmacology Nicotinic acid NLR Family, Pyrin Domain-Containing 3 Protein - antagonists & inhibitors NLR Family, Pyrin Domain-Containing 3 Protein - metabolism NLRP3 inflammasome Pharmacology Reactive oxygen species Reactive Oxygen Species - metabolism ROS SIRT1 SIRT1 protein Sirtuin 1 - metabolism Umbilical vein
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Summary:	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. •Nicotinic acid exerts anti-inflammatory property by inhibiting NLRP3 inflammasome.•Nicotinic acid blocks NLRP3 inflammasome activation in vascular endothelial cells.•The effect of nicotinic acid on NLRP3 inflammasome is mediated by SIRT1.•Nicotinic acid decreases the generation of ROS in vascular endothelial cells.•Nicotinic acid inhibits NLRP3 inflammasome activation partly through ROS.
ISSN:	1567-5769 1878-1705