Interleukin-1β-Treated Mesenchymal Stem Cells Inhibit Inflammation in Hippocampal Astrocytes Through Exosome-Activated Nrf-2 Signaling
Kai Liu,1,* Guo-Liang Cai,2,3 Zhe Zhuang,4,* Si-Ying Pei,1 Sheng-Nan Xu,5 Ya-Nan Wang,1 Hong Wang,1 Xin Wang,1 Cheng Cui,5 Man-Chao Sun,5 Si-Hui Guo,5 Kun-Ping Jia,1 Xiu-Zhen Wang,1 Guo-Feng Cai1 1Hanan Branch of Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine,...
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Dove Medical Press
2021
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oai:doaj.org-article:6823bd7fe4c94e239230fc7568a44d112021-12-02T13:43:49ZInterleukin-1β-Treated Mesenchymal Stem Cells Inhibit Inflammation in Hippocampal Astrocytes Through Exosome-Activated Nrf-2 Signaling1178-2013https://doaj.org/article/6823bd7fe4c94e239230fc7568a44d112021-02-01T00:00:00Zhttps://www.dovepress.com/interleukin-1beta-treated-mesenchymal-stem-cells-inhibit-inflammation--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Kai Liu,1,* Guo-Liang Cai,2,3 Zhe Zhuang,4,* Si-Ying Pei,1 Sheng-Nan Xu,5 Ya-Nan Wang,1 Hong Wang,1 Xin Wang,1 Cheng Cui,5 Man-Chao Sun,5 Si-Hui Guo,5 Kun-Ping Jia,1 Xiu-Zhen Wang,1 Guo-Feng Cai1 1Hanan Branch of Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, 150001, People’s Republic of China; 2Postdoctoral Research Workstation of Harbin Sport University, Harbin, 150001, People’s Republic of China; 3Department of Sport Science and Health, Harbin Sport University, Harbin, 150008, People’s Republic of China; 4Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, 150001, People’s Republic of China; 5Heilongjiang University of Traditional Chinese Medicine, Harbin, 150001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guo-Feng CaiHanan Branch of Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, 150001, People’s Republic of ChinaEmail cangjiong1973@163.comBackground: Interleukin-1β (IL-1)-treated mesenchymal stem cells (MSCs) and IL-1-MSCs-conditioned medium (CM) exert anti-inflammatory roles. Astrocytes are essential for the modulation of synaptic activity and neuronal homeostasis in the brain. Exosomes are the critical mediators in intercellular communication. However, the mechanism underlying the anti-inflammatory effect of IL-1-treated MSCs remains unknown.Methods: In this study, exosomes (IL-1-Exo) were isolated from IL-1-treated MSCs. In addition, lipopolysaccharide (LPS)-treated hippocampal astrocytes and status epilepticus (SE) mice were treated with IL-1-Exo. Inflammatory activity, astrogliosis, and cognitive performance were measured to determine the effect of IL-1-Exo on inflammation.Results: The results revealed that IL-1-Exo significantly inhibited LPS-induced astrogliosis and inflammatory responses of astrocytes. Also, IL-1-Exo reversed the LPS-induced effect on calcium signaling. The Nrf2 signaling pathway was associated with the effect of IL-1-Exo in LPS-treated astrocytes. Furthermore, IL-1-Exo reduced the inflammatory response and improved the cognitive performance of SE mice.Conclusion: The results suggest that IL-1-Exo inhibited LPS-induced inflammatory responses in astrocytes and SE mice and that the effect of IL-1-Exo was primarily mediated through the Nrf-2 signaling pathway. This study provides a new understanding of the molecular mechanism of inflammation-associated brain diseases and an avenue to develop nanotherapeutic agents for the treatment of inflammatory conditions in the brain.Keywords: mesenchymal stem cells, interleukin-1β, exosome, astrocyte, inflammation, Nrf-2Liu KCai GLZhuang ZPei SYXu SNWang YNWang HWang XCui CSun MCGuo SHJia KPWang XZCai GFDove Medical Pressarticlemesenchymal stem cellsinterleukin-1βexosomeastrocyteinflammationnrf-2Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 1423-1434 (2021) |
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DOAJ |
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EN |
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mesenchymal stem cells interleukin-1β exosome astrocyte inflammation nrf-2 Medicine (General) R5-920 |
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mesenchymal stem cells interleukin-1β exosome astrocyte inflammation nrf-2 Medicine (General) R5-920 Liu K Cai GL Zhuang Z Pei SY Xu SN Wang YN Wang H Wang X Cui C Sun MC Guo SH Jia KP Wang XZ Cai GF Interleukin-1β-Treated Mesenchymal Stem Cells Inhibit Inflammation in Hippocampal Astrocytes Through Exosome-Activated Nrf-2 Signaling |
| description |
Kai Liu,1,* Guo-Liang Cai,2,3 Zhe Zhuang,4,* Si-Ying Pei,1 Sheng-Nan Xu,5 Ya-Nan Wang,1 Hong Wang,1 Xin Wang,1 Cheng Cui,5 Man-Chao Sun,5 Si-Hui Guo,5 Kun-Ping Jia,1 Xiu-Zhen Wang,1 Guo-Feng Cai1 1Hanan Branch of Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, 150001, People’s Republic of China; 2Postdoctoral Research Workstation of Harbin Sport University, Harbin, 150001, People’s Republic of China; 3Department of Sport Science and Health, Harbin Sport University, Harbin, 150008, People’s Republic of China; 4Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, 150001, People’s Republic of China; 5Heilongjiang University of Traditional Chinese Medicine, Harbin, 150001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guo-Feng CaiHanan Branch of Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, 150001, People’s Republic of ChinaEmail cangjiong1973@163.comBackground: Interleukin-1β (IL-1)-treated mesenchymal stem cells (MSCs) and IL-1-MSCs-conditioned medium (CM) exert anti-inflammatory roles. Astrocytes are essential for the modulation of synaptic activity and neuronal homeostasis in the brain. Exosomes are the critical mediators in intercellular communication. However, the mechanism underlying the anti-inflammatory effect of IL-1-treated MSCs remains unknown.Methods: In this study, exosomes (IL-1-Exo) were isolated from IL-1-treated MSCs. In addition, lipopolysaccharide (LPS)-treated hippocampal astrocytes and status epilepticus (SE) mice were treated with IL-1-Exo. Inflammatory activity, astrogliosis, and cognitive performance were measured to determine the effect of IL-1-Exo on inflammation.Results: The results revealed that IL-1-Exo significantly inhibited LPS-induced astrogliosis and inflammatory responses of astrocytes. Also, IL-1-Exo reversed the LPS-induced effect on calcium signaling. The Nrf2 signaling pathway was associated with the effect of IL-1-Exo in LPS-treated astrocytes. Furthermore, IL-1-Exo reduced the inflammatory response and improved the cognitive performance of SE mice.Conclusion: The results suggest that IL-1-Exo inhibited LPS-induced inflammatory responses in astrocytes and SE mice and that the effect of IL-1-Exo was primarily mediated through the Nrf-2 signaling pathway. This study provides a new understanding of the molecular mechanism of inflammation-associated brain diseases and an avenue to develop nanotherapeutic agents for the treatment of inflammatory conditions in the brain.Keywords: mesenchymal stem cells, interleukin-1β, exosome, astrocyte, inflammation, Nrf-2 |
| format |
article |
| author |
Liu K Cai GL Zhuang Z Pei SY Xu SN Wang YN Wang H Wang X Cui C Sun MC Guo SH Jia KP Wang XZ Cai GF |
| author_facet |
Liu K Cai GL Zhuang Z Pei SY Xu SN Wang YN Wang H Wang X Cui C Sun MC Guo SH Jia KP Wang XZ Cai GF |
| author_sort |
Liu K |
| title |
Interleukin-1β-Treated Mesenchymal Stem Cells Inhibit Inflammation in Hippocampal Astrocytes Through Exosome-Activated Nrf-2 Signaling |
| title_short |
Interleukin-1β-Treated Mesenchymal Stem Cells Inhibit Inflammation in Hippocampal Astrocytes Through Exosome-Activated Nrf-2 Signaling |
| title_full |
Interleukin-1β-Treated Mesenchymal Stem Cells Inhibit Inflammation in Hippocampal Astrocytes Through Exosome-Activated Nrf-2 Signaling |
| title_fullStr |
Interleukin-1β-Treated Mesenchymal Stem Cells Inhibit Inflammation in Hippocampal Astrocytes Through Exosome-Activated Nrf-2 Signaling |
| title_full_unstemmed |
Interleukin-1β-Treated Mesenchymal Stem Cells Inhibit Inflammation in Hippocampal Astrocytes Through Exosome-Activated Nrf-2 Signaling |
| title_sort |
interleukin-1β-treated mesenchymal stem cells inhibit inflammation in hippocampal astrocytes through exosome-activated nrf-2 signaling |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/6823bd7fe4c94e239230fc7568a44d11 |
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