PMID- 29636842
OWN - NLM
STAT- MEDLINE
DCOM- 20180917
LR  - 20191210
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2018
DP  - 2018
TI  - A Novel Mechanism of Mesenchymal Stromal Cell-Mediated Protection against Sepsis: 
      Restricting Inflammasome Activation in Macrophages by Increasing Mitophagy and 
      Decreasing Mitochondrial ROS.
PG  - 3537609
LID - 10.1155/2018/3537609 [doi]
LID - 3537609
AB  - 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-1beta 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-1beta, 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.
FAU - Li, Shuang
AU  - Li S
AD  - Department of Cardiology & National Clinical Research Center of Geriatrics 
      Disease, Chinese PLA General Hospital, Beijing 100853, China.
AD  - Department of Cardiology, Chengdu Military General Hospital, Chengdu 610083, 
      China.
FAU - Wu, Hao
AU  - Wu H
AUID- ORCID: 0000-0003-4563-3365
AD  - Department of Toxicology, School of Public Health, Fourth Military Medical 
      University, Xi'an, Shaanxi 710032, China.
FAU - Han, Dong
AU  - Han D
AUID- ORCID: 0000-0002-0545-3338
AD  - Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi 710032, China.
FAU - Ma, Sai
AU  - Ma S
AUID- ORCID: 0000-0002-7638-9900
AD  - Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi 710032, China.
FAU - Fan, Wensi
AU  - Fan W
AD  - Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi 710032, China.
FAU - Wang, Yabin
AU  - Wang Y
AUID- ORCID: 0000-0002-7966-6117
AD  - Department of Cardiology & National Clinical Research Center of Geriatrics 
      Disease, Chinese PLA General Hospital, Beijing 100853, China.
FAU - Zhang, Ran
AU  - Zhang R
AD  - Department of Cardiology & National Clinical Research Center of Geriatrics 
      Disease, Chinese PLA General Hospital, Beijing 100853, China.
FAU - Fan, Miaomiao
AU  - Fan M
AD  - Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi 710032, China.
FAU - Huang, Yuesheng
AU  - Huang Y
AD  - Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined 
      Injury, Southwest Hospital, Third Military Medical University, Chongqing 400038, 
      China.
FAU - Fu, Xiaobing
AU  - Fu X
AUID- ORCID: 0000-0002-2465-1700
AD  - Department of Cardiology & National Clinical Research Center of Geriatrics 
      Disease, Chinese PLA General Hospital, Beijing 100853, China.
FAU - Cao, Feng
AU  - Cao F
AUID- ORCID: 0000-0002-1010-6429
AD  - Department of Cardiology & National Clinical Research Center of Geriatrics 
      Disease, Chinese PLA General Hospital, Beijing 100853, China.
LA  - eng
PT  - Journal Article
DEP - 20180213
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 0 (Inflammasomes)
RN  - 0 (Interleukin-1beta)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.3.2.27 (parkin protein)
RN  - EC 3.4.22.36 (Caspase 1)
SB  - IM
MH  - Animals
MH  - Caspase 1/metabolism
MH  - Cecum/pathology
MH  - Enzyme Activation
MH  - Inflammasomes/*metabolism
MH  - Inflammation/pathology
MH  - Injections, Intravenous
MH  - Interleukin-1beta/metabolism
MH  - Ligation
MH  - Macrophages/*metabolism/pathology
MH  - *Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/*cytology/metabolism
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Mitochondria/*metabolism
MH  - *Mitophagy
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
MH  - Punctures
MH  - Reactive Oxygen Species/*metabolism
MH  - Sepsis/prevention & control/*therapy
MH  - Survival Analysis
MH  - Ubiquitin-Protein Ligases/metabolism
PMC - PMC5831900
EDAT- 2018/04/11 06:00
MHDA- 2018/09/18 06:00
PMCR- 2018/02/13
CRDT- 2018/04/12 06:00
PHST- 2017/07/30 00:00 [received]
PHST- 2017/11/02 00:00 [revised]
PHST- 2017/12/04 00:00 [accepted]
PHST- 2018/04/12 06:00 [entrez]
PHST- 2018/04/11 06:00 [pubmed]
PHST- 2018/09/18 06:00 [medline]
PHST- 2018/02/13 00:00 [pmc-release]
AID - 10.1155/2018/3537609 [doi]
PST - epublish
SO  - Oxid Med Cell Longev. 2018 Feb 13;2018:3537609. doi: 10.1155/2018/3537609. 
      eCollection 2018.