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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Anisomycin protects against sepsis by attenuating IκB kinase-dependent NF-κB activation and inflammatory gene expression

  • Park, Gyoung Lim (Environmental Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Park, Minkyung (Environmental Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Min, Jeong-Ki (Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Park, Young-Jun (Environmental Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Chung, Su Wol (School of Biological Sciences, University of Ulsan) ;
  • Lee, Seon-Jin (Environmental Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
  • Received : 2021.05.12
  • Accepted : 2021.06.24
  • Published : 2021.11.30
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Abstract

Anisomycin is known to inhibit eukaryotic protein synthesis and has been established as an antibiotic and anticancer drug. However, the molecular targets of anisomycin and its mechanism of action have not been explained in macrophages. Here, we demonstrated the anti-inflammatory effects of anisomycin both in vivo and in vitro. We found that anisomycin decreased the mortality rate of macrophages in cecal ligation and puncture (CLP)- and lipopolysaccharide (LPS)-induced acute sepsis. It also declined the gene expression of proinflammatory mediators such as inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin-1β as well as the nitric oxide and proinflammatory cytokines production in macrophages subjected to LPS-induced acute sepsis. Furthermore, anisomycin attenuated nuclear factor (NF)-κB activation in LPS-induced macrophages, which correlated with the inhibition of phosphorylation of NF-κB-inducing kinase and IκB kinase, phosphorylation and IκBα proteolytic degradation, and NF-κB p65 subunit nuclear translocation. These results suggest that anisomycin prevented acute inflammation by inhibiting NF-κB-related inflammatory gene expression and could be a potential therapeutic candidate for sepsis.

Keywords

Acknowledgement

This research was funded by the National Research Foundation of South Korea (NRF - 2019R1A2C1086600), the KIST Institutional Program (Atmospheric Environment Research Program, 2E1390-21-P017), and the KRIBB Research Initiative Program (KGM 5322113).

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