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Arginine Regulates NLRP3 Inflammasome Activation Through SIRT1 in Vascular Endothelial Cells

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Abstract

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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Data Availability

The data and material used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank Professor Langchong He and Jie Zhang (Xi’an Jiaotong University, Xi’an, China) for their help in docking study.

Funding

This study was supported by the Qing Lan Project of Jiangsu Province, Natural Science Foundation for Higher Education Institutions of Jiangsu Province (No. 17KJB350012), Natural Science Foundation of Jiangsu Province (SBK2019022341), and Natural Science Foundation of Nantong (MS12018015).

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Authors and Affiliations

  1. School of Medicine, Nantong University, Nantong, China

    Miaomiao Zhang, Yujie Guo & Jiashuo Xu

  2. School of Pharmacy, Weifang Medical University, Weifang, China

    Yanxiang Li

  3. School of Pharmacy, Taizhou Polytechnic College, Taizhou, China

    Yanxiang Li

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  1. Miaomiao Zhang
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  2. Yanxiang Li
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  4. Jiashuo Xu
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Contributions

Experiments, data collection, and analysis were performed by Miaomiao Zhang, Yanxiang Li, and Jiashuo Xu. The first draft of the manuscript was written by Miaomiao Zhang. Yanxiang Li and Yujie Guo designed the study and revised the manuscript. All authors have read and approved the final manuscript.

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Correspondence to Yujie Guo.

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Zhang, M., Li, Y., Guo, Y. et al. Arginine Regulates NLRP3 Inflammasome Activation Through SIRT1 in Vascular Endothelial Cells. Inflammation 44, 1370–1380 (2021). https://doi.org/10.1007/s10753-021-01422-1

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  • DOI: https://doi.org/10.1007/s10753-021-01422-1

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