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A Novel Mechanism of Mesenchymal Stromal Cell-Mediated Protection against Sepsis: Restricting Inflammasome Activation in Macrophages by Increasing Mitophagy and Decreasing Mitochondrial ROS

Sepsis, a systemic inflammatory response to infection, is the leading cause of death in the intensive care unit (ICU). Previous studies indicated that mesenchymal stromal cells (MSCs) might have therapeutic potential against sepsis. The current study was designed to investigate the effects of MSCs o...

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Autores principales: Li, Shuang, Wu, Hao, Han, Dong, Ma, Sai, Fan, Wensi, Wang, Yabin, Zhang, Ran, Fan, Miaomiao, Huang, Yuesheng, Fu, Xiaobing, Cao, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5831900/
https://www.ncbi.nlm.nih.gov/pubmed/29636842
http://dx.doi.org/10.1155/2018/3537609
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author Li, Shuang
Wu, Hao
Han, Dong
Ma, Sai
Fan, Wensi
Wang, Yabin
Zhang, Ran
Fan, Miaomiao
Huang, Yuesheng
Fu, Xiaobing
Cao, Feng
author_facet Li, Shuang
Wu, Hao
Han, Dong
Ma, Sai
Fan, Wensi
Wang, Yabin
Zhang, Ran
Fan, Miaomiao
Huang, Yuesheng
Fu, Xiaobing
Cao, Feng
author_sort Li, Shuang
collection PubMed
description Sepsis, a systemic inflammatory response to infection, is the leading cause of death in the intensive care unit (ICU). Previous studies indicated that mesenchymal stromal cells (MSCs) might have therapeutic potential against sepsis. The current study was designed to investigate the effects of MSCs on sepsis and the underlying mechanisms focusing on inflammasome activation in macrophages. The results demonstrated that the bone marrow-derived mesenchymal stem cells (BMSCs) significantly increased the survival rate and organ function in cecal ligation and puncture (CLP) mice compared with the control-grouped mice. BMSCs significantly restricted NLRP3 inflammasome activation, suppressed the generation of mitochondrial ROS, and decreased caspase-1 and IL-1β activation when cocultured with bone marrow-derived macrophages (BMDMs), the effects of which could be abolished by Mito-TEMPO. Furthermore, the expression levels of caspase-1, IL-1β, and IL-18 in BMDMs were elevated after treatment with mitophagy inhibitor 3-MA. Thus, BMSCs exert beneficial effects on inhibiting NLRP3 inflammasome activation in macrophages primarily via both enhancing mitophagy and decreasing mitochondrial ROS. These findings suggest that restricting inflammasome activation in macrophages by increasing mitophagy and decreasing mitochondrial ROS might be a crucial mechanism for MSCs to combat sepsis.
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spelling pubmed-58319002018-04-10 A Novel Mechanism of Mesenchymal Stromal Cell-Mediated Protection against Sepsis: Restricting Inflammasome Activation in Macrophages by Increasing Mitophagy and Decreasing Mitochondrial ROS Li, Shuang Wu, Hao Han, Dong Ma, Sai Fan, Wensi Wang, Yabin Zhang, Ran Fan, Miaomiao Huang, Yuesheng Fu, Xiaobing Cao, Feng Oxid Med Cell Longev Research Article Sepsis, a systemic inflammatory response to infection, is the leading cause of death in the intensive care unit (ICU). Previous studies indicated that mesenchymal stromal cells (MSCs) might have therapeutic potential against sepsis. The current study was designed to investigate the effects of MSCs on sepsis and the underlying mechanisms focusing on inflammasome activation in macrophages. The results demonstrated that the bone marrow-derived mesenchymal stem cells (BMSCs) significantly increased the survival rate and organ function in cecal ligation and puncture (CLP) mice compared with the control-grouped mice. BMSCs significantly restricted NLRP3 inflammasome activation, suppressed the generation of mitochondrial ROS, and decreased caspase-1 and IL-1β activation when cocultured with bone marrow-derived macrophages (BMDMs), the effects of which could be abolished by Mito-TEMPO. Furthermore, the expression levels of caspase-1, IL-1β, and IL-18 in BMDMs were elevated after treatment with mitophagy inhibitor 3-MA. Thus, BMSCs exert beneficial effects on inhibiting NLRP3 inflammasome activation in macrophages primarily via both enhancing mitophagy and decreasing mitochondrial ROS. These findings suggest that restricting inflammasome activation in macrophages by increasing mitophagy and decreasing mitochondrial ROS might be a crucial mechanism for MSCs to combat sepsis. Hindawi 2018-02-13 /pmc/articles/PMC5831900/ /pubmed/29636842 http://dx.doi.org/10.1155/2018/3537609 Text en Copyright © 2018 Shuang Li et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Li, Shuang
Wu, Hao
Han, Dong
Ma, Sai
Fan, Wensi
Wang, Yabin
Zhang, Ran
Fan, Miaomiao
Huang, Yuesheng
Fu, Xiaobing
Cao, Feng
A Novel Mechanism of Mesenchymal Stromal Cell-Mediated Protection against Sepsis: Restricting Inflammasome Activation in Macrophages by Increasing Mitophagy and Decreasing Mitochondrial ROS
title A Novel Mechanism of Mesenchymal Stromal Cell-Mediated Protection against Sepsis: Restricting Inflammasome Activation in Macrophages by Increasing Mitophagy and Decreasing Mitochondrial ROS
title_full A Novel Mechanism of Mesenchymal Stromal Cell-Mediated Protection against Sepsis: Restricting Inflammasome Activation in Macrophages by Increasing Mitophagy and Decreasing Mitochondrial ROS
title_fullStr A Novel Mechanism of Mesenchymal Stromal Cell-Mediated Protection against Sepsis: Restricting Inflammasome Activation in Macrophages by Increasing Mitophagy and Decreasing Mitochondrial ROS
title_full_unstemmed A Novel Mechanism of Mesenchymal Stromal Cell-Mediated Protection against Sepsis: Restricting Inflammasome Activation in Macrophages by Increasing Mitophagy and Decreasing Mitochondrial ROS
title_short A Novel Mechanism of Mesenchymal Stromal Cell-Mediated Protection against Sepsis: Restricting Inflammasome Activation in Macrophages by Increasing Mitophagy and Decreasing Mitochondrial ROS
title_sort novel mechanism of mesenchymal stromal cell-mediated protection against sepsis: restricting inflammasome activation in macrophages by increasing mitophagy and decreasing mitochondrial ros
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5831900/
https://www.ncbi.nlm.nih.gov/pubmed/29636842
http://dx.doi.org/10.1155/2018/3537609
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