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

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 re...

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Autores principales: Oh, Byung Moo, Lee, Seon-Jin, Park, Gyoung Lim, Hwang, Yo Sep, Lim, Jeewon, Park, Eun Sun, Lee, Kyung Ho, Kim, Bo Yeon, Kwon, Yong Tae, Cho, Hee Jun, Lee, Hee Gu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947339/
https://www.ncbi.nlm.nih.gov/pubmed/31847346
http://dx.doi.org/10.3390/jcm8122210
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author Oh, Byung Moo
Lee, Seon-Jin
Park, Gyoung Lim
Hwang, Yo Sep
Lim, Jeewon
Park, Eun Sun
Lee, Kyung Ho
Kim, Bo Yeon
Kwon, Yong Tae
Cho, Hee Jun
Lee, Hee Gu
author_facet Oh, Byung Moo
Lee, Seon-Jin
Park, Gyoung Lim
Hwang, Yo Sep
Lim, Jeewon
Park, Eun Sun
Lee, Kyung Ho
Kim, Bo Yeon
Kwon, Yong Tae
Cho, Hee Jun
Lee, Hee Gu
author_sort Oh, Byung Moo
collection PubMed
description 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)-α, and interleukin (IL)-1β. Pretreatment with erastin in bone marrow-derived macrophages (BMDMs) significantly attenuated the expression of inducible nitric oxide synthase, cyclooxygenase-2, TNF-α, and IL-1β mRNA in response to LPS treatment. Furthermore, we also showed that erastin suppresses phosphorylation of IκB kinase β, phosphorylation and degradation of IκBα, and nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in LPS-stimulated BMDMs. Our findings suggest that erastin attenuates the inflammatory response by suppressing the NF-κB signaling pathway, resulting in inhibition of sepsis development. This study provides new insights regarding the potential therapeutic properties of erastin in sepsis.
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spelling pubmed-69473392020-01-13 Erastin Inhibits Septic Shock and Inflammatory Gene Expression via Suppression of the NF-κB Pathway Oh, Byung Moo Lee, Seon-Jin Park, Gyoung Lim Hwang, Yo Sep Lim, Jeewon Park, Eun Sun Lee, Kyung Ho Kim, Bo Yeon Kwon, Yong Tae Cho, Hee Jun Lee, Hee Gu J Clin Med Article 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)-α, and interleukin (IL)-1β. Pretreatment with erastin in bone marrow-derived macrophages (BMDMs) significantly attenuated the expression of inducible nitric oxide synthase, cyclooxygenase-2, TNF-α, and IL-1β mRNA in response to LPS treatment. Furthermore, we also showed that erastin suppresses phosphorylation of IκB kinase β, phosphorylation and degradation of IκBα, and nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in LPS-stimulated BMDMs. Our findings suggest that erastin attenuates the inflammatory response by suppressing the NF-κB signaling pathway, resulting in inhibition of sepsis development. This study provides new insights regarding the potential therapeutic properties of erastin in sepsis. MDPI 2019-12-14 /pmc/articles/PMC6947339/ /pubmed/31847346 http://dx.doi.org/10.3390/jcm8122210 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Oh, Byung Moo
Lee, Seon-Jin
Park, Gyoung Lim
Hwang, Yo Sep
Lim, Jeewon
Park, Eun Sun
Lee, Kyung Ho
Kim, Bo Yeon
Kwon, Yong Tae
Cho, Hee Jun
Lee, Hee Gu
Erastin Inhibits Septic Shock and Inflammatory Gene Expression via Suppression of the NF-κB Pathway
title Erastin Inhibits Septic Shock and Inflammatory Gene Expression via Suppression of the NF-κB Pathway
title_full Erastin Inhibits Septic Shock and Inflammatory Gene Expression via Suppression of the NF-κB Pathway
title_fullStr Erastin Inhibits Septic Shock and Inflammatory Gene Expression via Suppression of the NF-κB Pathway
title_full_unstemmed Erastin Inhibits Septic Shock and Inflammatory Gene Expression via Suppression of the NF-κB Pathway
title_short Erastin Inhibits Septic Shock and Inflammatory Gene Expression via Suppression of the NF-κB Pathway
title_sort erastin inhibits septic shock and inflammatory gene expression via suppression of the nf-κb pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947339/
https://www.ncbi.nlm.nih.gov/pubmed/31847346
http://dx.doi.org/10.3390/jcm8122210
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