KMID : 0624620210540110545
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BMB Reports 2021 Volume.54 No. 11 p.545 ~ p.550
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Anisomycin protects against sepsis by attenuating I¥êB kinase-dependent NF-¥êB activation and inflammatory gene expression
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Park Gyoung-Lim
Park Min-Kyung Min Jeong-Ki Park Young-Jun Chung Su-Wol Lee Seon-Jin
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Abstract
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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-¥á, and interleukin-1¥â as well as the nitric oxide and proinflammatory cytokines production in macrophages subjected to LPS-induced acute sepsis. Furthermore, anisomycin attenuated nuclear factor (NF)-¥êB activation in LPS-induced macrophages, which correlated with the inhibition of phosphorylation of NF-¥êBinducing kinase and I¥êB kinase, phosphorylation and I¥êB¥á proteolytic degradation, and NF-¥êB p65 subunit nuclear translocation. These results suggest that anisomycin prevented acute inflammation by inhibiting NF-¥êB-related inflammatory gene expression and could be a potential therapeutic candidate for sepsis.
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KEYWORD
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Anisomycin, Inflammation, Macrophages, NF-¥êB, Septic shock
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