Exosomes from adipose-derived stem cells alleviate the inflammation and oxidative stress via regulating Nrf2/HO-1 axis in macrophages
| Autor: | Jinxin Zhang, Dahai Hu, Yunchuan Wang, Xujie Wang, Jin Li, Yanhui Jia, Kaituo Liu, Jing Wang, Kuo Shen, Weixia Cai, Ming Zhao, Shaohui Li |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
NF-E2-Related Factor 2 Adipose tissue Inflammation Exosomes Biochemistry Proinflammatory cytokine Flow cytometry 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Physiology (medical) medicine Humans Macrophage Kelch-Like ECH-Associated Protein 1 medicine.diagnostic_test Chemistry Macrophages Stem Cells Regeneration (biology) Microvesicles Cell biology Oxidative Stress 030104 developmental biology medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | Free Radical Biology and Medicine. 165:54-66 |
| ISSN: | 0891-5849 |
| Popis: | ADSCs exosomes, an important means of intercellular communication, can regulate an array of biological processes, including promoting tissue repairs and regeneration, and attenuating inflammation. In this study, we found that ADSCs exosomes could polarize macrophage to an anti-inflammatory phenotype via regulating the expression of Nrf2 and HO-1, and improve inflammatory reaction and injury of multi-organ in sepsis. We revealed that ADSCs exosomes could alleviate LPS induced accumulation of ROS and the expression of inflammatory cytokines IL-1β, TNF-α, and IL-6 in macrophages. Western blot and Flow cytometry results indicated that expression of M1 markers (iNOS and CD86) in LPS stimulated macrophages were significantly declined, while M2 (Arg1 and CD206) were enhanced when pretreated with ADSCs exosomes. Besides, the stress-related molecule HO-1 was upregulated when pretreated with ADSCs exosomes. Further H0-1 interference experiment indicated that anti-inflammatory effect of ADSCs exosomes was dependent on HO-1. Moreover, ADSCs exosomes enhanced expression and nucleus translocation of Nrf2, while downregulated its negative mediator Keap1. In in vivo sepsis models, intravenous injection of ADSCs exosomes relieved inflammatory cytokines storm and organ injury, while promoted expression of HO-1. In conclusion, we proved that ADSCs exosomes alleviated LPS induced inflammation and exerted protective effect in sepsis via regulating Nrf2/HO-1 expression. |
| Databáze: | OpenAIRE |
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