Fasudil regulates T cell responses through polarization of BV-2 cells in mice experimental autoimmune encephalomyelitis

Chen, Chan; Li, Yanhua; Zhang, Qiong; Yu, Jie‐Zhong; Zhao, Yongfei; Ma, Cun‐Gen; Xiao, Bao‐Guo

doi:10.1038/aps.2014.68

Cited by 24 publications

(16 citation statements)

References 47 publications

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“…The mechanisms of Fasudil action include anti‐inflammation, synaptogenesis, and M2 polarization in microglia . In addition, Fasudil ameliorated the severity of EAE, accompanied by rebalance of helper T cell 1 (Th1) and Th17, macrophage polarization from M1 to M2 phenotype, and less infiltration of inflammatory cells in spinal cord . By regulating peripheral immune dysfunction, Fasudil attenuated neuroinflammation, demyelination, and axonal loss in EAE model .…”

Section: Discussionmentioning

confidence: 99%

Retracted: Effect of Fasudil on remyelination following cuprizone‐induced demyelination

et al. 2019

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BackgroundMultiple sclerosis is characterized by demyelination/remyelination, neuroinflammation, and neurodegeneration. Cuprizone (CPZ)‐induced toxic demyelination is an experimental animal model commonly used to study demyelination and remyelination in the central nervous system. Fasudil is one of the most thoroughly studied Rho kinase inhibitors.MethodsFollowing CPZ exposure, the degree of demyelination in the brain of male C57BL/6 mice was assessed by Luxol fast blue, Black Gold II, myelin basic protein immunofluorescent staining, and Western blot. The effect of Fasudil on behavioral change was determined using elevated plus maze test and pole test. The possible mechanisms of Fasudil action were examined by immunohistochemistry, flow cytometry, ELISA, and dot blot.ResultsFasudil improved behavioral abnormalities, inhibited microglia‐mediated neuroinflammation, and promoted astrocyte‐derived nerve growth factor and ciliary neurotrophic factor, which should contribute to protection and regeneration of oligodendrocytes. In addition, Fasudil inhibited the production of myelin oligodendrocyte glycoprotein antibody and the infiltration of peripheral CD4+ T cells and CD68+ macrophages, which appears to be related to the integrity of the blood‐brain barrier.ConclusionThese results provide evidence for the therapeutic potential of Fasudil in CPZ‐induced demyelination. However, how Fasudil acts on microglia, astrocytes, and immune cells remains to be further explored.

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Section: Discussionmentioning

confidence: 99%

Retracted: Effect of Fasudil on remyelination following cuprizone‐induced demyelination

et al. 2019

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“…Furthermore, many immune cells are capable of expressing IL‐10, including Tregs and alternative activation macrophages which, in turn, further increase the levels of IL‐10 and promote the differentiation of additional regulatory cells. Together, this establishes an anti‐inflammatory milieu capable of suppressing effector T cell functions . Aside from producing IL‐10, alternative activation macrophages are critical for promoting reparative and anti‐inflammatory effects .…”

Section: Discussionmentioning

confidence: 99%

“…Aside from producing IL‐10, alternative activation macrophages are critical for promoting reparative and anti‐inflammatory effects . Together, many approaches to shift the phenotype of macrophages from classical to alternative activation have been executed that demonstrate substantial improvements in EAE .…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory Effects of Adipose Stromal Vascular Fraction Cells Promote Alternative Activation Macrophages to Repair Tissue Damage

et al. 2017

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The pathogenesis of many diseases is driven by the interactions between helper T (T ) cells and macrophages. The phenotypes of these cells are functional dichotomies that are persuaded according to the surrounding milieu. In both multiple sclerosis and the experimental autoimmune encephalomyelitis (EAE) model, T 1 and T 17 cells propagate autoimmune signaling and inflammation in the peripheral lymphoid tissues. In turn, this proinflammatory repertoire promotes the classical activation, formerly the M1-type, macrophages. Together, these cells infiltrate into the central nervous system (CNS) tissues and generate inflammatory and demyelinating lesions. Our most recent report demonstrated the immunomodulatory and anti-inflammatory effects of adipose stromal vascular fraction (SVF) cells and adipose-derived stem cells (ASCs) that led to functional, immunological, and pathological improvements in the EAE model. Here, a deeper investigation revealed the induction of regulatory T cells and alternative activation, or M2-type, macrophages in the periphery followed by the presence of alternative activation macrophages, reduced cellular infiltrates, and attenuation of neuroinflammation in CNS tissues following intraperitoneal administration of these treatments. Spleens from treated EAE mice revealed diminished T 1 and T 17 cell activities and were markedly higher in the levels of anti-inflammatory cytokine interleukin-10. Interestingly, SVF cells were more effective than ASCs at mediating these beneficial changes, which were attributed to their localization to the spleens after administration. Together, SVF cells rapidly and robustly attenuated the propagation of autoimmune signaling in the periphery that provided a permissive milieu in the CNS for repair and possibly regeneration. Stem Cells 2017;35:2198-2207.

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“…This suggests that microglia polarization serves as a potential target for elevating anti-inflammatory and repair-promoting interactions between microglia and infiltrated peripheral cells. The therapeutic potential of promoting microglia M2 polarization by Fasudil supplement has been explored in the EAE model, in which the downregulation of IL-17 secretion from T cells was mediated by M2 polarized microglia after Fasudil treatment (81). Collectively, interactions between microglia and peripheral immune cells show a repair-promoting effect mainly through promoting subtype conversion of microglia.…”

Section: Interactions Between Microglia and Infiltrated Cellsmentioning

confidence: 99%

Communications Between Peripheral and the Brain-Resident Immune System in Neuronal Regeneration After Stroke

et al. 2020

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Cerebral ischemia may cause irreversible neural network damage and result in functional deficits. Targeting neuronal repair after stroke potentiates the formation of new connections, which can be translated into a better functional outcome. Innate and adaptive immune responses in the brain and the periphery triggered by ischemic damage participate in regulating neural repair after a stroke. Immune cells in the blood circulation and gut lymphatic tissues that have been shaped by immune components including gut microbiota and metabolites can infiltrate the ischemic brain and, once there, influence neuronal regeneration either directly or by modulating the properties of brain-resident immune cells. Immune-related signalings and metabolites from the gut microbiota can also directly alter the phenotypes of resident immune cells to promote neuronal regeneration. In this review, we discuss several potential mechanisms through which peripheral and brain-resident immune components can cooperate to promote first the resolution of neuroinflammation and subsequently to improved neural regeneration and a better functional recovery. We propose that new insights into discovery of regulators targeting pro-regenerative process in this complex neuro-immune network may lead to novel strategies for neuronal regeneration.

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Fasudil regulates T cell responses through polarization of BV-2 cells in mice experimental autoimmune encephalomyelitis

Cited by 24 publications

References 47 publications

Retracted: Effect of Fasudil on remyelination following cuprizone‐induced demyelination

Retracted: Effect of Fasudil on remyelination following cuprizone‐induced demyelination

Immunomodulatory Effects of Adipose Stromal Vascular Fraction Cells Promote Alternative Activation Macrophages to Repair Tissue Damage

Communications Between Peripheral and the Brain-Resident Immune System in Neuronal Regeneration After Stroke

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