4.5 Article

Arginine Regulates NLRP3 Inflammasome Activation Through SIRT1 in Vascular Endothelial Cells

期刊

INFLAMMATION
卷 44, 期 4, 页码 1370-1380

出版社

SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10753-021-01422-1

关键词

arginine; sirtuin 1; NLRP3 inflammasome; endothelial cells

资金

  1. Qing Lan Project of Jiangsu Province
  2. Natural Science Foundation for Higher Education Institutions of Jiangsu Province [17KJB350012]
  3. Natural Science Foundation of Jiangsu Province [SBK2019022341]
  4. Natural Science Foundation of Nantong [MS12018015]

向作者/读者索取更多资源

The semi-essential amino acid L-arginine (Arg) has been shown to attenuate inflammatory response during cardiovascular disease by suppressing NLRP3 inflammasome activation and increasing SIRT1 expression, partially through inhibition of ROS production. This suggests a potential mechanism for Arg's inhibitory effect on NLRP3 inflammasome activation in vascular endothelial cells.
L-arginine (Arg), a semi-essential amino acid, has recently been shown to attenuate inflammatory response during cardiovascular disease. NLRP3 inflammasome serves a central role in amplification of cellular inflammation. In this study, we aimed to confirm the modulatory effect of Arg on NLRP3 inflammasome and the underlying mechanisms in vascular endothelial cells (ECs). Arg suppressed NLRP3 inflammasome activation in ECs stimulated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP). Moreover, treatment with Arg increased the expression of the deacetylase sirtuin 1 (SIRT1) in ECs. Importantly, knockdown of SIRT1 abolished the inhibitory potential of Arg on the activation of NLRP3 inflammasome. Further study indicated that Arg also alleviated LPS plus ATP-induced the generation of reactive oxygen species (ROS) in ECs. In addition, Arg may regulate NLRP3 inflammasome activation partly through suppression of ROS production. In combination, we speculate that Arg exerts an inhibitory effect on the activation of NLRP3 inflammasome in ECs, which may be partly mediated by SIRT1 and ROS.

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