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Anisomycin protects against sepsis by attenuating I kappa B kinase-dependent NF-kappa B activation and inflammatory gene expression

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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-alpha, and interleukin-1 beta as well as the nitric oxide and proinflammatory cytokines production in macrophages subjected to LPS-induced acute sepsis. Furthermore, anisomycin attenuated nuclear factor (NF)-kappa B activation in LPS-induced macrophages, which correlated with the inhibition of phosphorylation of NF-kappa B-inducing kinase and I kappa B kinase, phosphorylation and I.Ba proteolytic degradation, and NF-kappa B p65 subunit nuclear translocation. These results suggest that anisomycin prevented acute inflammation by inhibiting NF-kappa B-related inflammatory gene expression and could be a potential therapeutic candidate for sepsis.
Author(s)
박경임박민경민정기박용준정수월이선진
Issued Date
2021
Type
Article
Keyword
AnisomycinsepsisNF-κB activationgene expression
DOI
10.5483/BMBRep.2021.54.11.063
URI
https://oak.ulsan.ac.kr/handle/2021.oak/9586
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_nrf_kci_oai_kci_go_kr_ARTI_9890104&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Anisomycin%20protects%20against%20sepsis%20by%20attenuating%20I%20kappa%20B%20kinase-dependent%20NF-kappa%20B%20activation%20and%20inflammatory%20gene%20expression&offset=0&pcAvailability=true
Publisher
BMB REPORTS
Location
대한민국
Language
영어
ISSN
1976-6696
Citation Volume
54
Citation Number
11
Citation Start Page
545
Citation End Page
550
Appears in Collections:
Natural Science > Biological Sciences
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