1. Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Attenuate LPS-Induced ARDS by Modulating Macrophage Polarization Through Inhibiting Glycolysis in Macrophages
- Author
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Xin Lv, Huanping Zhou, Xiaoting Hu, Xuan Shi, Lina Zhu, Huimin Deng, Hao Yang, Meiyun Liu, Mansi Wang, Yuanli Chen, Li Zheng, Zhengyu He, Lingmin Wu, and Juan Wei
- Subjects
Lipopolysaccharides ,Male ,Macrophage polarization ,Bone Marrow Cells ,Inflammation ,030204 cardiovascular system & hematology ,Lung injury ,Exosomes ,Critical Care and Intensive Care Medicine ,Mice ,03 medical and health sciences ,0302 clinical medicine ,stomatognathic system ,medicine ,Animals ,Respiratory Distress Syndrome ,Chemistry ,Macrophages ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,030208 emergency & critical care medicine ,Microvesicles ,medicine.anatomical_structure ,Cell culture ,Emergency Medicine ,Alveolar macrophage ,Cancer research ,Bone marrow ,medicine.symptom ,Glycolysis - Abstract
Macrophages play a key role in the development of sepsis-induced acute respiratory distress syndrome (ARDS). Recent evidence has proved that glycolysis plays an important role in regulating macrophage polarization through metabolic reprogramming. Bone marrow mesenchymal stem cells (BMSCs) can alleviate sepsis-induced lung injury and possess potent immunomodulatory and immunosuppressive properties via secreting exosomes. However, it is unknown whether BMSCs-derived exosomes exert their therapeutic effect against sepsis-induced lung injury by inhibiting glycolysis in macrophages. Therefore, the present study aimed to evaluate the anti-inflammatory effects of exosomes released from BMSCs on acute lung injury induced by lipopolysaccharide (LPS) in mice and explored the possible underlying mechanisms in vitro and in vivo. We found that BMSCs inhibited M1 polarization and promoted M2 polarization in MH-S cells (a murine alveolar macrophage cell line) by releasing exosomes. Further experiments showed that exosomes secreted by BMSCs modulated LPS-treated MH-S cells polarization by inhibiting cellular glycolysis. Moreover, our results showed that BMSCs-derived exosomes down-regulated the expression of several essential proteins of glycolysis via inhibition of hypoxia-inducible factor 1 (HIF-1)α. Finally, a model of LPS-induced ARDS in mice was established, we found that BMSCs-derived exosomes ameliorated the LPS-induced inflammation and lung pathological damage. Meanwhile, we found that intratracheal delivery of BMSCs-derived exosomes effectively down-regulated LPS-induced glycolysis in mice lung tissue. These findings reveal new mechanisms of BMSCs-derived exosomes in regulating macrophage polarization which may provide novel strategies for the prevention and treatment of LPS-induced ARDS.
- Published
- 2020