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Erastin Inhibits Septic Shock and Inflammatory Gene Expression via Suppression of the NF-?B Pathway.


ABSTRACT: Sepsis is a life-threatening condition that is caused by an abnormal immune response to infection and can lead to tissue damage, organ failure, and death. Erastin is a small molecule capable of initiating ferroptotic cell death in cancer cells. However, the function of erastin in the inflammatory response during sepsis remains unknown. Here, we showed that erastin ameliorates septic shock induced by cecal ligation and puncture or lipopolysaccharides (LPS) in mice, which was associated with a reduced production of inflammatory mediators such as nitric oxide, tumor necrosis factor (TNF)-?, and interleukin (IL)-1?. Pretreatment with erastin in bone marrow-derived macrophages (BMDMs) significantly attenuated the expression of inducible nitric oxide synthase, cyclooxygenase-2, TNF-?, and IL-1? mRNA in response to LPS treatment. Furthermore, we also showed that erastin suppresses phosphorylation of I?B kinase ?, phosphorylation and degradation of I?B?, and nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B) in LPS-stimulated BMDMs. Our findings suggest that erastin attenuates the inflammatory response by suppressing the NF-?B signaling pathway, resulting in inhibition of sepsis development. This study provides new insights regarding the potential therapeutic properties of erastin in sepsis.

SUBMITTER: Oh BM 

PROVIDER: S-EPMC6947339 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Erastin Inhibits Septic Shock and Inflammatory Gene Expression via Suppression of the NF-κB Pathway.

Oh Byung Moo BM   Lee Seon-Jin SJ   Park Gyoung Lim GL   Hwang Yo Sep YS   Lim Jeewon J   Park Eun Sun ES   Lee Kyung Ho KH   Kim Bo Yeon BY   Kwon Yong Tae YT   Cho Hee Jun HJ   Lee Hee Gu HG  

Journal of clinical medicine 20191214 12


Sepsis is a life-threatening condition that is caused by an abnormal immune response to infection and can lead to tissue damage, organ failure, and death. Erastin is a small molecule capable of initiating ferroptotic cell death in cancer cells. However, the function of erastin in the inflammatory response during sepsis remains unknown. Here, we showed that erastin ameliorates septic shock induced by cecal ligation and puncture or lipopolysaccharides (LPS) in mice, which was associated with a red  ...[more]

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