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Article

Simvastatin inhibits the inflammation and oxidative stress of human neutrophils in sepsis via autophagy induction

  • Authors:
    • Li Xu
    • Xiao-Min Wu
    • Yu-Kun Zhang
    • Ming-Jie Huang
    • Jun Chen
  • View Affiliations / Copyright

    Affiliations: Intensive Care Unit, Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
  • Article Number: 25
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    Published online on: November 22, 2021
       https://doi.org/10.3892/mmr.2021.12541
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Abstract

Simvastatin exerts a protective effect during sepsis (SP) in animal models; however, the underlying mechanism is not completely understood, particularly in human SP. Neutrophils are a critical effector in the host inflammatory response to SP. Therefore, the present study aimed to investigate the effect of simvastatin on neutrophils in human SP. Neutrophils were isolated from the peripheral venous blood of adult patients with SP and healthy volunteers (HP). Cell viability was analyzed using the MTT assay. Intracellular reactive oxygen species (ROS) generation and the concentrations of inflammatory mediators were also assessed using flow cytometry and ELISA. The results demonstrated that the cell viability of neutrophils from the SP group was significantly decreased compared with that in the HP group, and that treatment with simvastatin partly reversed the reduced cell viability. Furthermore, simvastatin administration significantly decreased ROS production and the concentrations of TNF‑α and IL‑6, which were significantly increased in neutrophils isolated from the SP group. Simvastatin also enhanced autophagy induction, as indicated by the promotion of the conversion of LC3I to LC3II and the increased expression levels of Beclin 1 in SP neutrophils. Treatment with 3‑methyladenine, an autophagy inhibitor, completely blocked the protective effects of simvastatin on neutrophils from SP, including the effects of simvastatin on the inhibition of inflammation, oxidative stress and improving cell viability. Collectively, the present study provided evidence for the simvastatin‑induced autophagic process of neutrophils involved in human SP, which protects neutrophils and partially attenuates the inflammatory response and oxidative stress. Therefore, the augmentation of neutrophil autophagy may serve as a potential therapeutic target for patients with SP.
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Copy and paste a formatted citation
Spandidos Publications style
Xu L, Wu X, Zhang Y, Huang M and Chen J: Simvastatin inhibits the inflammation and oxidative stress of human neutrophils in sepsis via autophagy induction. Mol Med Rep 25: 25, 2022.
APA
Xu, L., Wu, X., Zhang, Y., Huang, M., & Chen, J. (2022). Simvastatin inhibits the inflammation and oxidative stress of human neutrophils in sepsis via autophagy induction. Molecular Medicine Reports, 25, 25. https://doi.org/10.3892/mmr.2021.12541
MLA
Xu, L., Wu, X., Zhang, Y., Huang, M., Chen, J."Simvastatin inhibits the inflammation and oxidative stress of human neutrophils in sepsis via autophagy induction". Molecular Medicine Reports 25.1 (2022): 25.
Chicago
Xu, L., Wu, X., Zhang, Y., Huang, M., Chen, J."Simvastatin inhibits the inflammation and oxidative stress of human neutrophils in sepsis via autophagy induction". Molecular Medicine Reports 25, no. 1 (2022): 25. https://doi.org/10.3892/mmr.2021.12541
Copy and paste a formatted citation
x
Spandidos Publications style
Xu L, Wu X, Zhang Y, Huang M and Chen J: Simvastatin inhibits the inflammation and oxidative stress of human neutrophils in sepsis via autophagy induction. Mol Med Rep 25: 25, 2022.
APA
Xu, L., Wu, X., Zhang, Y., Huang, M., & Chen, J. (2022). Simvastatin inhibits the inflammation and oxidative stress of human neutrophils in sepsis via autophagy induction. Molecular Medicine Reports, 25, 25. https://doi.org/10.3892/mmr.2021.12541
MLA
Xu, L., Wu, X., Zhang, Y., Huang, M., Chen, J."Simvastatin inhibits the inflammation and oxidative stress of human neutrophils in sepsis via autophagy induction". Molecular Medicine Reports 25.1 (2022): 25.
Chicago
Xu, L., Wu, X., Zhang, Y., Huang, M., Chen, J."Simvastatin inhibits the inflammation and oxidative stress of human neutrophils in sepsis via autophagy induction". Molecular Medicine Reports 25, no. 1 (2022): 25. https://doi.org/10.3892/mmr.2021.12541
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