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Article

MCC950 improves lipopolysaccharide‑induced systemic inflammation in mice by relieving pyroptosis in blood neutrophils

  • Authors:
    • Runfeng Miao
    • Jian Huang
  • View Affiliations / Copyright

    Affiliations: Department of Emergency Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
  • Article Number: 417
    |
    Published online on: July 13, 2023
       https://doi.org/10.3892/etm.2023.12117
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Abstract

Sepsis is an infection‑induced systemic inflammatory response syndrome accompanied by multiple organ injury and failure. MCC950, an inhibitor of NLR family pyrin domain containing 3 (NLRP3), can alleviate the inflammatory response and relieve inflammation‑induced injury. The aim of the present study was to explore the efficacy of MCC950 in lipopolysaccharide (LPS)‑induced inflammation and elucidate the underlying mechanisms. Based on a prior study, C57BL/6 mice were divided into three groups: Control, LPS, and LPS + MCC950. The mice were administered 10 mg/kg LPS to induce sepsis and 10 mg/kg MCC950 to treat sepsis 6 h before and after LPS injection. Histopathological imaging revealed organ morphology and damage during inflammation, and MCC950 alleviated organ damage and dysfunction. MCC950 prevented LPS‑induced inflammatory responses by reducing inflammatory cytokine levels in the blood. To explore the mechanism by which MCC950 functions, blood neutrophils were isolated and a series of tests were performed. As revealed by measuring reactive oxygen species levels and Annexin V/PI staining of neutrophils, MCC950 reduced oxidative stress and programmed death induced by LPS. Western blotting was used to assess the protein levels of pyroptosis‑related markers, including GSDMD, NLRP3, and caspase‑1, in neutrophils to further explore the form of death. MCC950 reduced LPS‑induced pyroptosis in neutrophils. The results of the survival analysis revealed that MCC950 increased the survival rates of mice within 72 h of LPS injection. MCC950 may be an effective treatment for sepsis that targets neutrophil pyroptosis.
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Copy and paste a formatted citation
Spandidos Publications style
Miao R and Huang J: MCC950 improves lipopolysaccharide‑induced systemic inflammation in mice by relieving pyroptosis in blood neutrophils. Exp Ther Med 26: 417, 2023.
APA
Miao, R., & Huang, J. (2023). MCC950 improves lipopolysaccharide‑induced systemic inflammation in mice by relieving pyroptosis in blood neutrophils. Experimental and Therapeutic Medicine, 26, 417. https://doi.org/10.3892/etm.2023.12117
MLA
Miao, R., Huang, J."MCC950 improves lipopolysaccharide‑induced systemic inflammation in mice by relieving pyroptosis in blood neutrophils". Experimental and Therapeutic Medicine 26.3 (2023): 417.
Chicago
Miao, R., Huang, J."MCC950 improves lipopolysaccharide‑induced systemic inflammation in mice by relieving pyroptosis in blood neutrophils". Experimental and Therapeutic Medicine 26, no. 3 (2023): 417. https://doi.org/10.3892/etm.2023.12117
Copy and paste a formatted citation
x
Spandidos Publications style
Miao R and Huang J: MCC950 improves lipopolysaccharide‑induced systemic inflammation in mice by relieving pyroptosis in blood neutrophils. Exp Ther Med 26: 417, 2023.
APA
Miao, R., & Huang, J. (2023). MCC950 improves lipopolysaccharide‑induced systemic inflammation in mice by relieving pyroptosis in blood neutrophils. Experimental and Therapeutic Medicine, 26, 417. https://doi.org/10.3892/etm.2023.12117
MLA
Miao, R., Huang, J."MCC950 improves lipopolysaccharide‑induced systemic inflammation in mice by relieving pyroptosis in blood neutrophils". Experimental and Therapeutic Medicine 26.3 (2023): 417.
Chicago
Miao, R., Huang, J."MCC950 improves lipopolysaccharide‑induced systemic inflammation in mice by relieving pyroptosis in blood neutrophils". Experimental and Therapeutic Medicine 26, no. 3 (2023): 417. https://doi.org/10.3892/etm.2023.12117
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