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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Interferon-β alleviates sepsis by SIRT1-mediated blockage of endothelial glycocalyx shedding

  • Suhong Duan (Department of Microbiology, Jeonbuk National University Medical School) ;
  • Seung-Gook Kim (Department of Microbiology, Jeonbuk National University Medical School) ;
  • Hyung-Jin Lim (Department of Microbiology, Jeonbuk National University Medical School) ;
  • Hwa-Ryung Song (Department of Microbiology, Jeonbuk National University Medical School) ;
  • Myung-Kwan Han (Department of Microbiology, Jeonbuk National University Medical School)
  • Received : 2023.03.06
  • Accepted : 2023.04.03
  • Published : 2023.05.31
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Abstract

Sepsis is a life-threatening multi-organ dysfunction with high mortality caused by the body's improper response to microbial infection. No new effective therapy has emerged that can adequately treat patients with sepsis. We previously demonstrated that interferon-β (IFN-β) protects against sepsis via sirtuin 1-(SIRT1)-mediated immunosuppression. Another study also reported its significant protective effect against acute respiratory distress syndrome, a complication of severe sepsis, in human patients. However, the IFN-β effect cannot solely be explained by SIRT1-mediated immunosuppression, since sepsis induces immunosuppression in patients. Here, we show that IFN-β, in combination with nicotinamide riboside (NR), alleviates sepsis by blocking endothelial damage via SIRT1 activation. IFN-β plus NR protected against cecal ligation puncture-(CLP)-induced sepsis in wild-type mice, but not in endothelial cell-specific Sirt1 knockout (EC-Sirt1 KO) mice. IFN-β upregulated SIRT1 protein expression in endothelial cells in a protein synthesis-independent manner. IFN-β plus NR reduced the CLP-induced increase in in vivo endothelial permeability in wild-type, but not EC-Sirt1 KO mice. IFN-β plus NR suppressed lipopolysaccharide-induced up-regulation of heparinase 1, but the effect was abolished by Sirt1 knockdown in endothelial cells. Our results suggest that IFN-β plus NR protects against endothelial damage during sepsis via activation of the SIRT1/heparinase 1 pathway.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea [grant number 2017R1A5A2015061].

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