Progesterone therapy induces an M1 to M2 switch in microglia phenotype and suppresses NLRP3 inflammasome in a cuprizone-induced demyelination mouse model

Aryanpour, Roya; Pasbakhsh, Parichehr; Zibara, Kazem; Namjoo, Zeinab; Boroujeni, Fatemeh Beigi; Shahbeigi, Saeed; Kashani, Iraj Ragerdi; Beyer, Cordian; Zendehdel, Adib

doi:10.1016/j.intimp.2017.08.007

Cited by 121 publications

(86 citation statements)

References 66 publications

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“…In addition, oligodendrocytes are highly vulnerable in an inflammatory environment . In this study, we found that Iba‐1 + microglia were aggregated or increased in the corpus callosum and striatum, demonstrating that CPZ induced microglia activation, which is consistent with other studies . Activated microglia are known to contribute to neurodegeneration via various cytotoxic molecules .…”

Section: Discussionsupporting

confidence: 91%

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: Discussionsupporting

confidence: 91%

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

et al. 2019

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“…[126][127][128] An overview of differences between M1 and M2 macrophages as well as transitions between them concerning surface markers, inflammation-related receptors, cytokines, and chemokines as well as their respective receptors, expression of iNOS, and formation of ROS is found in Ref. 125 Importantly, the M1 vs M2 polarization known from macrophages in peripheral tissues is found in a very similar way in microglia, [129][130][131] findings that will gain substantial relevance in the fields of inflammaging and neurodegeneration, that is, other important areas of melatonin research.…”

Section: Macrophage Polarizationmentioning

confidence: 99%

Melatonin in macrophage biology: Current understanding and future perspectives

Xia

Chen

Zeng

et al. 2019

Journal of Pineal Research

152

126

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Melatonin is a ubiquitous hormone found in various organisms and highly affects the function of immune cells. In this review, we summarize the current understanding of the significance of melatonin in macrophage biology and the beneficial effects of melatonin in macrophage‐associated diseases. Enzymes associated with synthesis of melatonin, as well as membrane receptors for melatonin, are found in macrophages. Indeed, melatonin influences the phenotype polarization of macrophages. Mechanistically, the roles of melatonin in macrophages are related to several cellular signaling pathways, such as NF‐κB, STATs, and NLRP3/caspase‐1. Notably, miRNAs (eg, miR‐155/‐34a/‐23a), cellular metabolic pathways (eg, α‐KG, HIF‐1α, and ROS), and mitochondrial dynamics and mitophagy are also involved. Thus, melatonin modulates the development and progression of various macrophage‐associated diseases, such as cancer and rheumatoid arthritis. This review provides a better understanding about the importance of melatonin in macrophage biology and macrophage‐associated diseases.

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“…NLRP3 and IL-18 mRNA expression dramatically increased after cuprizone treatment and the adverse effect was reversed after progesterone therapy. Therefore, progesterone was concluded as having ameliorative effects to induce remyelination [44]. Some studies have determined the intervention of agonist or antagonist in disease amelioration.…”

Section: Role Of Macrophages In Brain Injuries and Neuron Protectionmentioning

confidence: 99%

Chemopreventive Effects of Phytochemicals and Medicines on M1/M2 Polarized Macrophage Role in Inflammation-Related Diseases

Koh

Yang

Lai

et al. 2018

IJMS

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Macrophages can polarize into two different states (M1 and M2), which play contrasting roles during pathogenesis or tissue damage. M1 polarized macrophages produce pro-inflammatory cytokines and mediators resulting in inflammation, while M2 macrophages have an anti-inflammatory effect. Secretion of appropriate cytokines and chemokines from macrophages can lead to the modification of the microenvironment for bridging innate and adaptive immune responses. Increasing evidence suggests that polarized macrophages are pivotal for disease progression, and the regulation of macrophage polarization may provide a new approach in therapeutic treatment of inflammation-related diseases, including cancer, obesity and metabolic diseases, fibrosis in organs, brain damage and neuron injuries, and colorectal disease. Polarized macrophages affect the microenvironment by secreting cytokines and chemokines while cytokines or mediators that are produced by resident cells or tissues may also influence macrophages behavior. The interplay of macrophages and other cells can affect disease progression, and therefore, understanding the activation of macrophages and the interaction between polarized macrophages and disease progression is imperative prior to taking therapeutic or preventive actions. Manipulation of macrophages can be an entry point for disease improvement, but the mechanism and potential must be understood. In this review, some advanced studies regarding the role of macrophages in different diseases, potential mechanisms involved, and intervention of drugs or phytochemicals, which are effective on macrophage polarization, will be discussed.

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Progesterone therapy induces an M1 to M2 switch in microglia phenotype and suppresses NLRP3 inflammasome in a cuprizone-induced demyelination mouse model

Cited by 121 publications

References 66 publications

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

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

Melatonin in macrophage biology: Current understanding and future perspectives

Chemopreventive Effects of Phytochemicals and Medicines on M1/M2 Polarized Macrophage Role in Inflammation-Related Diseases

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