Targeting the shift from M1 to M2 macrophages in experimental autoimmune encephalomyelitis mice treated with fasudil.
We observed the therapeutic effect of Fasudil and explored its mechanisms in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Fasudil, a selective Rho kinase (ROCK) inhibitor, was injected intraperitoneally at 40 mg/kg/d in early and late stages of EAE ind...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2013-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3572131?pdf=render |
id |
doaj-8d5c239eaaf14ac9a1f3ae3d62fff025 |
---|---|
record_format |
Article |
spelling |
doaj-8d5c239eaaf14ac9a1f3ae3d62fff0252020-11-25T02:47:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5484110.1371/journal.pone.0054841Targeting the shift from M1 to M2 macrophages in experimental autoimmune encephalomyelitis mice treated with fasudil.Chunyun LiuYanhua LiJiezhong YuLing FengShaowei HouYueting LiuMingfang GuoYong XieJian MengHaifei ZhangBaoguo XiaoCungen MaWe observed the therapeutic effect of Fasudil and explored its mechanisms in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Fasudil, a selective Rho kinase (ROCK) inhibitor, was injected intraperitoneally at 40 mg/kg/d in early and late stages of EAE induction. Fasudil ameliorated the clinical severity of EAE at different stages, and decreased the expression of ROCK-II in spleen, accompanied by an improvement in demyelination and inhibition of inflammatory cells. Fasudil mainly inhibited CD4(+)IL-17(+) T cells in early treatment, but also elevated CD4(+)IL-10(+) regulatory T cells and IL-10 production in late treatment. The treatment of Fasudil shifted inflammatory M1 to anti-inflammatory M2 macrophages in both early and late treatment, being shown by inhibiting CD16/32, iNOS, IL-12, TLR4 and CD40 and increasing CD206, Arg-1, IL-10 and CD14 in spleen. By using Western blot and immunohistochemistry, iNOS and Arg-1, as two most specific markers for M1 and M2, was inhibited or induced in splenic macrophages and spinal cords of EAE mice treated with Fasudil. In vitro experiments also indicate that Fasudil shifts M1 to M2 phenotype, which does not require the participation or auxiliary of other cells. The polarization of M2 macrophages was associated with the decrease of inflammatory cytokine IL-1β, TNF-α and MCP-1. These results demonstrate that Fasudil has therapeutic potential in EAE possibly through inducing the polarization of M2 macrophages and inhibiting inflammatory responses.http://europepmc.org/articles/PMC3572131?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chunyun Liu Yanhua Li Jiezhong Yu Ling Feng Shaowei Hou Yueting Liu Mingfang Guo Yong Xie Jian Meng Haifei Zhang Baoguo Xiao Cungen Ma |
spellingShingle |
Chunyun Liu Yanhua Li Jiezhong Yu Ling Feng Shaowei Hou Yueting Liu Mingfang Guo Yong Xie Jian Meng Haifei Zhang Baoguo Xiao Cungen Ma Targeting the shift from M1 to M2 macrophages in experimental autoimmune encephalomyelitis mice treated with fasudil. PLoS ONE |
author_facet |
Chunyun Liu Yanhua Li Jiezhong Yu Ling Feng Shaowei Hou Yueting Liu Mingfang Guo Yong Xie Jian Meng Haifei Zhang Baoguo Xiao Cungen Ma |
author_sort |
Chunyun Liu |
title |
Targeting the shift from M1 to M2 macrophages in experimental autoimmune encephalomyelitis mice treated with fasudil. |
title_short |
Targeting the shift from M1 to M2 macrophages in experimental autoimmune encephalomyelitis mice treated with fasudil. |
title_full |
Targeting the shift from M1 to M2 macrophages in experimental autoimmune encephalomyelitis mice treated with fasudil. |
title_fullStr |
Targeting the shift from M1 to M2 macrophages in experimental autoimmune encephalomyelitis mice treated with fasudil. |
title_full_unstemmed |
Targeting the shift from M1 to M2 macrophages in experimental autoimmune encephalomyelitis mice treated with fasudil. |
title_sort |
targeting the shift from m1 to m2 macrophages in experimental autoimmune encephalomyelitis mice treated with fasudil. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
We observed the therapeutic effect of Fasudil and explored its mechanisms in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Fasudil, a selective Rho kinase (ROCK) inhibitor, was injected intraperitoneally at 40 mg/kg/d in early and late stages of EAE induction. Fasudil ameliorated the clinical severity of EAE at different stages, and decreased the expression of ROCK-II in spleen, accompanied by an improvement in demyelination and inhibition of inflammatory cells. Fasudil mainly inhibited CD4(+)IL-17(+) T cells in early treatment, but also elevated CD4(+)IL-10(+) regulatory T cells and IL-10 production in late treatment. The treatment of Fasudil shifted inflammatory M1 to anti-inflammatory M2 macrophages in both early and late treatment, being shown by inhibiting CD16/32, iNOS, IL-12, TLR4 and CD40 and increasing CD206, Arg-1, IL-10 and CD14 in spleen. By using Western blot and immunohistochemistry, iNOS and Arg-1, as two most specific markers for M1 and M2, was inhibited or induced in splenic macrophages and spinal cords of EAE mice treated with Fasudil. In vitro experiments also indicate that Fasudil shifts M1 to M2 phenotype, which does not require the participation or auxiliary of other cells. The polarization of M2 macrophages was associated with the decrease of inflammatory cytokine IL-1β, TNF-α and MCP-1. These results demonstrate that Fasudil has therapeutic potential in EAE possibly through inducing the polarization of M2 macrophages and inhibiting inflammatory responses. |
url |
http://europepmc.org/articles/PMC3572131?pdf=render |
work_keys_str_mv |
AT chunyunliu targetingtheshiftfromm1tom2macrophagesinexperimentalautoimmuneencephalomyelitismicetreatedwithfasudil AT yanhuali targetingtheshiftfromm1tom2macrophagesinexperimentalautoimmuneencephalomyelitismicetreatedwithfasudil AT jiezhongyu targetingtheshiftfromm1tom2macrophagesinexperimentalautoimmuneencephalomyelitismicetreatedwithfasudil AT lingfeng targetingtheshiftfromm1tom2macrophagesinexperimentalautoimmuneencephalomyelitismicetreatedwithfasudil AT shaoweihou targetingtheshiftfromm1tom2macrophagesinexperimentalautoimmuneencephalomyelitismicetreatedwithfasudil AT yuetingliu targetingtheshiftfromm1tom2macrophagesinexperimentalautoimmuneencephalomyelitismicetreatedwithfasudil AT mingfangguo targetingtheshiftfromm1tom2macrophagesinexperimentalautoimmuneencephalomyelitismicetreatedwithfasudil AT yongxie targetingtheshiftfromm1tom2macrophagesinexperimentalautoimmuneencephalomyelitismicetreatedwithfasudil AT jianmeng targetingtheshiftfromm1tom2macrophagesinexperimentalautoimmuneencephalomyelitismicetreatedwithfasudil AT haifeizhang targetingtheshiftfromm1tom2macrophagesinexperimentalautoimmuneencephalomyelitismicetreatedwithfasudil AT baoguoxiao targetingtheshiftfromm1tom2macrophagesinexperimentalautoimmuneencephalomyelitismicetreatedwithfasudil AT cungenma targetingtheshiftfromm1tom2macrophagesinexperimentalautoimmuneencephalomyelitismicetreatedwithfasudil |
_version_ |
1724755064874074112 |