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Oxidative Medicine and Cellular Longevity
Volume 2018 (2018), Article ID 3537609, 15 pages
Research Article

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

1Department of Cardiology & National Clinical Research Center of Geriatrics Disease, Chinese PLA General Hospital, Beijing 100853, China
2Department of Cardiology, Chengdu Military General Hospital, Chengdu 610083, China
3Department of Toxicology, School of Public Health, Fourth Military Medical University, Xi’an, Shaanxi 710032, China
4Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi 710032, China
5Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing 400038, China

Correspondence should be addressed to Feng Cao

Received 30 July 2017; Revised 2 November 2017; Accepted 4 December 2017; Published 13 February 2018

Academic Editor: Nabil Eid

Copyright © 2018 Shuang Li et al. 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.


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.