Anisomycin protects against sepsis by attenuating IκB kinase-dependent NF-κB activation and inflammatory gene expression
| Autor: | Seon-Jin Lee, Minkyung Park, Young-Jun Park, Jeong-Ki Min, Gyoung Lim Park, Su Wol Chung |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Lipopolysaccharides
Inflammation IκB kinase Pharmacology Nitric Oxide Biochemistry Article NF-κB Nitric oxide Proinflammatory cytokine Mice chemistry.chemical_compound Septic shock Sepsis medicine Animals Molecular Biology Anisomycin Protein Synthesis Inhibitors Kinase Macrophages NF-kappa B General Medicine Mice Inbred C57BL IκBα Gene Expression Regulation chemistry Female I-kappa B Proteins Tumor necrosis factor alpha Inflammation Mediators medicine.symptom |
| Zdroj: | BMB Reports |
| ISSN: | 1976-670X |
| Popis: | 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-κBinducing 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. [BMB Reports 2021; 54(11): 545-550]. |
| Databáze: | OpenAIRE |
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