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Bronchoalveolar Lavage Exosomes in Lipopolysaccharide-induced Septic Lung Injury
Published on: May 21, 2018
MSCs-derived extracellular vesicles alleviate sepsis-associated liver dysfunction by inhibiting macrophage
Lei Pei1, Ranran Li2, Xiaofeng Wang1
1Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract:
Sepsis-associated liver dysfunction (SALD) aggravates the disease progression and prognosis of patients. Macrophages in the liver play a crucial role in the occurrence and development of SALD. Human umbilical cord mesenchymal stem cells (MSCs), by secreting extracellular vesicles (EVs), show beneficial effects in various inflammatory diseases. However, whether MSC-derived EVs (MSC-EVs) could ameliorate the inflammatory response in liver macrophages and the underlying mechanisms remain unclear. In this study, a mouse model of sepsis induced by lipopolysaccharide (LPS) challenge was used to investigate the immunomodulatory functions of MSC-EVs in SALD. LPS-stimulated primary Kupffer cells (KCs) and Raw264.7 were used to further explore the potential mechanisms of MSC-EVs in regulating the inflammatory response of macrophages. The results showed that MSC-EVs alleviated liver tissue injury and facilitated the polarization of M1 to M2 macrophages. Further in vitro studies confirmed that MSC-EVs treatment significantly downregulated the expression of several enzymes related to glycolysis and reduced the glycolytic flux by inhibiting hypoxia-inducible factor 1α (HIF-1α) expression, thus effectively inhibiting the inflammatory responses of macrophages. These findings reveal that the application of MSC-EVs might be a potential therapeutic strategy for treating SALD.
Insights
Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) show promise for treating sepsis-associated liver dysfunction (SALD). MSC-EVs reduce inflammation in liver macrophages by inhibiting glycolysis via hypoxia-inducible factor 1α (HIF-1α).
Area of Science:
- Immunology
- Cell Biology
- Hepatology
Background:
- Sepsis-associated liver dysfunction (SALD) worsens patient outcomes.
- Liver macrophages are key players in SALD pathogenesis.
- Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have shown anti-inflammatory effects.
Purpose of the Study:
- To investigate the therapeutic potential of MSC-EVs in SALD.
- To elucidate the mechanisms by which MSC-EVs modulate liver macrophage inflammation.
Main Methods:
- A mouse model of sepsis induced by lipopolysaccharide (LPS) challenge.
- In vitro studies using LPS-stimulated Kupffer cells (KCs) and Raw264.7 macrophages.
- Analysis of macrophage polarization, glycolytic enzymes, glycolytic flux, and hypoxia-inducible factor 1α (HIF-1α) expression.
Main Results:
- MSC-EVs treatment alleviated liver injury in a sepsis mouse model.
- MSC-EVs promoted the M1 to M2 macrophage polarization shift.
- MSC-EVs downregulated glycolytic enzymes and reduced glycolytic flux by inhibiting HIF-1α, suppressing macrophage inflammation.
Conclusions:
- MSC-EVs demonstrate immunomodulatory functions in SALD.
- MSC-EVs exert anti-inflammatory effects on liver macrophages by targeting glycolysis.
- MSC-EVs represent a potential therapeutic strategy for SALD.
