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2018 ; 2018
(ä): 3537609
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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
#MMPMID29636842
Li S
; Wu H
; Han D
; Ma S
; Fan W
; Wang Y
; Zhang R
; Fan M
; Huang Y
; Fu X
; Cao F
Oxid Med Cell Longev
2018[]; 2018
(ä): 3537609
PMID29636842
show ga
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-1? 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-1?, 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.