Matrine Inhibits CNS Autoimmunity Through an IFN-β-Dependent Mechanism
Matrine (MAT), a quinolizidine alkaloid component derived from the root of Sophora flavescens, suppresses experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS), by inducing the production of immunomodulatory molecules, e.g., IL-10. In an effort to find the upst...
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doaj-2d8f09852f2e4880a7acf34dd56c52f02020-11-25T03:14:02ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-09-011110.3389/fimmu.2020.569530569530Matrine Inhibits CNS Autoimmunity Through an IFN-β-Dependent MechanismYao-Juan Chu0Wen-Di Ma1Rodolfo Thome2Jie-Dan Ping3Fang-Zhou Liu4Meng-Ru Wang5Ming-Liang Zhang6Guangxian Zhang7Lin Zhu8Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Neurology, Thomas Jefferson University, Philadelphia, PA, United StatesDepartment of Clinical Laboratory, Key Clinical Laboratory of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Province Chinese Medicine Research Institute, Zhengzhou, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Province Engineering Laboratory for Clinical Evaluation Technology of Chinese Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, ChinaDepartment of Neurology, Thomas Jefferson University, Philadelphia, PA, United StatesDepartment of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaMatrine (MAT), a quinolizidine alkaloid component derived from the root of Sophora flavescens, suppresses experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS), by inducing the production of immunomodulatory molecules, e.g., IL-10. In an effort to find the upstream pathway(s) of the mechanism underlying these effects, we have tested certain upregulated immunomodulatory molecules. Among them, we found increased levels of IL-27 and IFN-β, one of the first-line MS therapies. Indeed, while low levels of IFN-β production in sera and type I interferon receptor (IFNAR1) expression in spinal cord of saline-treated control EAE mice were detected, they were significantly increased after MAT treatment. Increased numbers of CD11b+IFN-β+ microglia/infiltrating macrophages were observed in the CNS of MAT-treated mice. The key role of IFN-β induction in the suppressive effect of MAT on EAE was further verified by administration of anti-IFN-β neutralizing antibody, which largely reversed the therapeutic effect of MAT. Further, we found that, while MAT treatment induced production of IL-27 and IL-10 by CNS microglia/macrophages, this effect was significantly reduced by IFN-β neutralizing antibody. Finally, the role of IFN-β in MAT-induced IL-27 and IL-10 production was further confirmed in human monocytes in vitro. Together, our study demonstrates that MAT exerts its therapeutic effect in EAE through an IFN-β/IL-27/IL-10 pathway, and is likely a novel, safe, low-cost, and effective therapy as an alternative to exogenous IFN-β for MS.https://www.frontiersin.org/article/10.3389/fimmu.2020.569530/fullmatrinemultiple sclerosisexperimental autoimmune encephalomyelitisIFN-βIL-10IL-27 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yao-Juan Chu Wen-Di Ma Rodolfo Thome Jie-Dan Ping Fang-Zhou Liu Meng-Ru Wang Ming-Liang Zhang Guangxian Zhang Lin Zhu |
spellingShingle |
Yao-Juan Chu Wen-Di Ma Rodolfo Thome Jie-Dan Ping Fang-Zhou Liu Meng-Ru Wang Ming-Liang Zhang Guangxian Zhang Lin Zhu Matrine Inhibits CNS Autoimmunity Through an IFN-β-Dependent Mechanism Frontiers in Immunology matrine multiple sclerosis experimental autoimmune encephalomyelitis IFN-β IL-10 IL-27 |
author_facet |
Yao-Juan Chu Wen-Di Ma Rodolfo Thome Jie-Dan Ping Fang-Zhou Liu Meng-Ru Wang Ming-Liang Zhang Guangxian Zhang Lin Zhu |
author_sort |
Yao-Juan Chu |
title |
Matrine Inhibits CNS Autoimmunity Through an IFN-β-Dependent Mechanism |
title_short |
Matrine Inhibits CNS Autoimmunity Through an IFN-β-Dependent Mechanism |
title_full |
Matrine Inhibits CNS Autoimmunity Through an IFN-β-Dependent Mechanism |
title_fullStr |
Matrine Inhibits CNS Autoimmunity Through an IFN-β-Dependent Mechanism |
title_full_unstemmed |
Matrine Inhibits CNS Autoimmunity Through an IFN-β-Dependent Mechanism |
title_sort |
matrine inhibits cns autoimmunity through an ifn-β-dependent mechanism |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2020-09-01 |
description |
Matrine (MAT), a quinolizidine alkaloid component derived from the root of Sophora flavescens, suppresses experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS), by inducing the production of immunomodulatory molecules, e.g., IL-10. In an effort to find the upstream pathway(s) of the mechanism underlying these effects, we have tested certain upregulated immunomodulatory molecules. Among them, we found increased levels of IL-27 and IFN-β, one of the first-line MS therapies. Indeed, while low levels of IFN-β production in sera and type I interferon receptor (IFNAR1) expression in spinal cord of saline-treated control EAE mice were detected, they were significantly increased after MAT treatment. Increased numbers of CD11b+IFN-β+ microglia/infiltrating macrophages were observed in the CNS of MAT-treated mice. The key role of IFN-β induction in the suppressive effect of MAT on EAE was further verified by administration of anti-IFN-β neutralizing antibody, which largely reversed the therapeutic effect of MAT. Further, we found that, while MAT treatment induced production of IL-27 and IL-10 by CNS microglia/macrophages, this effect was significantly reduced by IFN-β neutralizing antibody. Finally, the role of IFN-β in MAT-induced IL-27 and IL-10 production was further confirmed in human monocytes in vitro. Together, our study demonstrates that MAT exerts its therapeutic effect in EAE through an IFN-β/IL-27/IL-10 pathway, and is likely a novel, safe, low-cost, and effective therapy as an alternative to exogenous IFN-β for MS. |
topic |
matrine multiple sclerosis experimental autoimmune encephalomyelitis IFN-β IL-10 IL-27 |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2020.569530/full |
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