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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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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. |
format | Online Article Text |
id | pubmed-6947339 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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