Cargando…

Microglia Polarization from M1 toward M2 Phenotype Is Promoted by Astragalus Polysaccharides Mediated through Inhibition of miR-155 in Experimental Autoimmune Encephalomyelitis

Activated microglia is considered to be major mediators of the neuroinflammatory environment in demyelinating diseases of the central nervous system (CNS). Activated microglia are mainly polarized into M1 type, which plays a role in promoting inflammation and demyelinating. However, the proportion o...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Xiaojun, Ma, Jinyun, Ding, Guiqing, Gong, Qianyi, Wang, Yuanhua, Yu, Hua, Cheng, Xiaodong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8720009/
https://www.ncbi.nlm.nih.gov/pubmed/34976303
http://dx.doi.org/10.1155/2021/5753452
_version_ 1784625061168152576
author Liu, Xiaojun
Ma, Jinyun
Ding, Guiqing
Gong, Qianyi
Wang, Yuanhua
Yu, Hua
Cheng, Xiaodong
author_facet Liu, Xiaojun
Ma, Jinyun
Ding, Guiqing
Gong, Qianyi
Wang, Yuanhua
Yu, Hua
Cheng, Xiaodong
author_sort Liu, Xiaojun
collection PubMed
description Activated microglia is considered to be major mediators of the neuroinflammatory environment in demyelinating diseases of the central nervous system (CNS). Activated microglia are mainly polarized into M1 type, which plays a role in promoting inflammation and demyelinating. However, the proportion of microglia polarized into M2 type is relatively low, which cannot fully play the role of anti-inflammatory and resistance to demyelinating. Our previous study found that Astragalus polysaccharides (APS) has an immunomodulatory effect and can inhibit neuroinflammation and demyelination in experimental autoimmune encephalomyelitis (EAE), which is a classic animal model of CNS demyelinating disease. In this study, we found that APS was effective in treating EAE mice. It restored microglia balance by inhibiting the polarization of microglia to M1-like phenotype and promoting the polarization of microglia to M2-like phenotype in vivo and in vitro. miR-155 is a key factor in regulating microglia polarization. We found that APS could inhibit the expression level of miR-155 in vivo and in vitro. Furthermore, we performed transfection overexpression and blocking experiments. The results showed that miR-155 mediated the polarization of microglia M1/M2 phenotype, while the selective inhibitor of miR-155 attenuated the inhibition of APS on microglia M1 phenotype and eliminated the promotion of APS on microglia M2 phenotype. Microglia can secrete IL-1α, TNF-α, and C1q after polarizing into M1 type and induce the activation of A1 neurotoxic astrocytes, further aggravating neuroinflammation and demyelination. APS reduced the secretion of IL-1α, TNF-α, and C1q by activated microglia, thus inhibited the formation of A1 neurotoxic astrocytes. In summary, our study suggests that APS regulates the polarization of microglia from M1 to M2 phenotype by inhibiting the miR-155, reduces the secretion of inflammatory factors, and inhibits the activation of neurotoxic astrocytes, thus effectively treating EAE.
format Online
Article
Text
id pubmed-8720009
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-87200092022-01-01 Microglia Polarization from M1 toward M2 Phenotype Is Promoted by Astragalus Polysaccharides Mediated through Inhibition of miR-155 in Experimental Autoimmune Encephalomyelitis Liu, Xiaojun Ma, Jinyun Ding, Guiqing Gong, Qianyi Wang, Yuanhua Yu, Hua Cheng, Xiaodong Oxid Med Cell Longev Research Article Activated microglia is considered to be major mediators of the neuroinflammatory environment in demyelinating diseases of the central nervous system (CNS). Activated microglia are mainly polarized into M1 type, which plays a role in promoting inflammation and demyelinating. However, the proportion of microglia polarized into M2 type is relatively low, which cannot fully play the role of anti-inflammatory and resistance to demyelinating. Our previous study found that Astragalus polysaccharides (APS) has an immunomodulatory effect and can inhibit neuroinflammation and demyelination in experimental autoimmune encephalomyelitis (EAE), which is a classic animal model of CNS demyelinating disease. In this study, we found that APS was effective in treating EAE mice. It restored microglia balance by inhibiting the polarization of microglia to M1-like phenotype and promoting the polarization of microglia to M2-like phenotype in vivo and in vitro. miR-155 is a key factor in regulating microglia polarization. We found that APS could inhibit the expression level of miR-155 in vivo and in vitro. Furthermore, we performed transfection overexpression and blocking experiments. The results showed that miR-155 mediated the polarization of microglia M1/M2 phenotype, while the selective inhibitor of miR-155 attenuated the inhibition of APS on microglia M1 phenotype and eliminated the promotion of APS on microglia M2 phenotype. Microglia can secrete IL-1α, TNF-α, and C1q after polarizing into M1 type and induce the activation of A1 neurotoxic astrocytes, further aggravating neuroinflammation and demyelination. APS reduced the secretion of IL-1α, TNF-α, and C1q by activated microglia, thus inhibited the formation of A1 neurotoxic astrocytes. In summary, our study suggests that APS regulates the polarization of microglia from M1 to M2 phenotype by inhibiting the miR-155, reduces the secretion of inflammatory factors, and inhibits the activation of neurotoxic astrocytes, thus effectively treating EAE. Hindawi 2021-12-24 /pmc/articles/PMC8720009/ /pubmed/34976303 http://dx.doi.org/10.1155/2021/5753452 Text en Copyright © 2021 Xiaojun Liu et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Liu, Xiaojun
Ma, Jinyun
Ding, Guiqing
Gong, Qianyi
Wang, Yuanhua
Yu, Hua
Cheng, Xiaodong
Microglia Polarization from M1 toward M2 Phenotype Is Promoted by Astragalus Polysaccharides Mediated through Inhibition of miR-155 in Experimental Autoimmune Encephalomyelitis
title Microglia Polarization from M1 toward M2 Phenotype Is Promoted by Astragalus Polysaccharides Mediated through Inhibition of miR-155 in Experimental Autoimmune Encephalomyelitis
title_full Microglia Polarization from M1 toward M2 Phenotype Is Promoted by Astragalus Polysaccharides Mediated through Inhibition of miR-155 in Experimental Autoimmune Encephalomyelitis
title_fullStr Microglia Polarization from M1 toward M2 Phenotype Is Promoted by Astragalus Polysaccharides Mediated through Inhibition of miR-155 in Experimental Autoimmune Encephalomyelitis
title_full_unstemmed Microglia Polarization from M1 toward M2 Phenotype Is Promoted by Astragalus Polysaccharides Mediated through Inhibition of miR-155 in Experimental Autoimmune Encephalomyelitis
title_short Microglia Polarization from M1 toward M2 Phenotype Is Promoted by Astragalus Polysaccharides Mediated through Inhibition of miR-155 in Experimental Autoimmune Encephalomyelitis
title_sort microglia polarization from m1 toward m2 phenotype is promoted by astragalus polysaccharides mediated through inhibition of mir-155 in experimental autoimmune encephalomyelitis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8720009/
https://www.ncbi.nlm.nih.gov/pubmed/34976303
http://dx.doi.org/10.1155/2021/5753452
work_keys_str_mv AT liuxiaojun microgliapolarizationfromm1towardm2phenotypeispromotedbyastragaluspolysaccharidesmediatedthroughinhibitionofmir155inexperimentalautoimmuneencephalomyelitis
AT majinyun microgliapolarizationfromm1towardm2phenotypeispromotedbyastragaluspolysaccharidesmediatedthroughinhibitionofmir155inexperimentalautoimmuneencephalomyelitis
AT dingguiqing microgliapolarizationfromm1towardm2phenotypeispromotedbyastragaluspolysaccharidesmediatedthroughinhibitionofmir155inexperimentalautoimmuneencephalomyelitis
AT gongqianyi microgliapolarizationfromm1towardm2phenotypeispromotedbyastragaluspolysaccharidesmediatedthroughinhibitionofmir155inexperimentalautoimmuneencephalomyelitis
AT wangyuanhua microgliapolarizationfromm1towardm2phenotypeispromotedbyastragaluspolysaccharidesmediatedthroughinhibitionofmir155inexperimentalautoimmuneencephalomyelitis
AT yuhua microgliapolarizationfromm1towardm2phenotypeispromotedbyastragaluspolysaccharidesmediatedthroughinhibitionofmir155inexperimentalautoimmuneencephalomyelitis
AT chengxiaodong microgliapolarizationfromm1towardm2phenotypeispromotedbyastragaluspolysaccharidesmediatedthroughinhibitionofmir155inexperimentalautoimmuneencephalomyelitis