Targeting the Shift from M1 to M2 Macrophages in Experimental Autoimmune Encephalomyelitis Mice Treated with Fasudil

Liu, Chunyun; Li, Yanhua; Yu, Jie‐Zhong; Li, Feng; Hou, Shuxun; Liu, Yueting; Guo, Mingfang; Xie, Yong; Jian, Meng; Zhang, Haifei; Xiao, Bailu; Ma, Cun‐Gen

doi:10.1371/journal.pone.0054841

Cited by 183 publications

(167 citation statements)

References 51 publications

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“…Analysis of the spinal cord of treated mice showed that SHED-CM induced a shift in the macrophage phenotype from an M1 proinflammatory phenotype to an M2 anti-inflammatory phenotype, as well as suppressed the expression of proinflammatory mediators. Treatments resulting in shifts from M1 to M2 phenotypes were shown to suppress EAE (37,38). In addition, our in vitro analysis indicated that the presence of SHED-CM inhibited the proliferation of…”

Section: Discussionmentioning

confidence: 66%

Conditioned Medium from the Stem Cells of Human Exfoliated Deciduous Teeth Ameliorates Experimental Autoimmune Encephalomyelitis

Shimojima

Takeuchi

Jin

et al. 2016

The Journal of Immunology

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Multiple sclerosis (MS) is a major neuroinflammatory demyelinating disease of the CNS. Current MS treatments, including immunomodulators and immunosuppressants, do not result in complete remission. Stem cells from human exfoliated deciduous teeth (SHEDs) are mesenchymal stem cells derived from dental pulp. Both SHED and SHED-conditioned medium (SHED-CM) exhibit immunomodulatory and regenerative activities and have the potential to treat various diseases. In this study, we investigated the efficacy of SHED-CM in treating experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. EAE mice treated with a single injection of SHED-CM exhibited significantly improved disease scores, reduced demyelination and axonal injury, and reduced inflammatory cell infiltration and proinflammatory cytokine expression in the spinal cord, which was associated with a shift in the microglia/macrophage phenotype from M1 to M2. SHED-CM also inhibited the proliferation of myelin oligodendrocyte glycoprotein–specific CD4+ T cells, as well as their production of proinflammatory cytokines in vitro. Treatment of EAE mice with the secreted ectodomain of sialic acid–binding Ig-like lectin-9, a major component of SHED-CM, recapitulated the effects of SHED-CM treatment. Our data suggest that SHED-CM and secreted ectodomain of sialic acid–binding Ig-like lectin-9 may be novel therapeutic treatments for autoimmune diseases, such as MS.

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Section: Discussionmentioning

confidence: 66%

Conditioned Medium from the Stem Cells of Human Exfoliated Deciduous Teeth Ameliorates Experimental Autoimmune Encephalomyelitis

Shimojima

Takeuchi

Jin

et al. 2016

The Journal of Immunology

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“…Failure to switch from a predominance of M1 to M2 causes to the perpetuation of chronic inflammation. 8 Imbalance in the M1/M2 ratio has been associated with cardiovascular diseases such as atherosclerosis, 9 metabolism-associated diseases such as diabetes and metabolic syndrome, 10 and autoimmune diseases such as multiple sclerosis, 11 systemic lupus erythematosus, 12 Crohn's disease 13 and rheumatoid arthritis. Persistence of M1 macrophages in the local inflammatory response can also prevent the resolution of inflammation in several chronic skin diseases, such as diabetes-associated skin ulcerations, 14 chronic venous ulcers, 15 and atopic dermatitis.…”

Section: Introductionmentioning

confidence: 99%

Targeting CD64 mediates elimination of M1 but not M2 macrophages in vitro and in cutaneous inflammation in mice and patient biopsies

Hristodorov¹,

Mladenov²,

Felbert³

et al. 2015

mAbs

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(2015) Targeting CD64 mediates elimination of M1 but not M2 macrophages in vitro and in cutaneous inflammation in mice and patient biopsies, mAbs, 7:5, 853-862, DOI: 10.1080/19420862.2015 To link to this article: https://doi.org/10. 1080/19420862.2015 (classical M1 or alternative M2), that play a differential role in immune regulation. In general, the M1 contribute to onset of inflammation, whereas the M2 orchestrate resolution and repair, whereby failure to switch from predominantly M1 to M2 reinforces a pro-inflammatory environment and chronic inflammation. Here, we show selective elimination of M1 macrophages in vitro by a range of CD64-targeted immunotoxins, including H22 (scFv)-ETA'. After re-polarization of already polarized macrophages, still only M1 polarization showed sensitivity toward CD64-directed immunotoxins. The selectivity for M1 was found linked to reduced endosomal protease activity in M1 macrophages as demonstrated by inhibition of endosomal proteases. Using the H22(scFv)-ETA' in a transgenic mouse model for chronic cutaneous inflammation, the M1 specificity was confirmed in vivo and a beneficial effect on inflammation demonstrated. Also ex vivo on skin biopsies from atopic dermatitis and diabetes type II patients with chronically-inflamed skin, a clear M1 specific effect was found. This indicates the potential relevance for human application. Our data show that targeting M1 macrophages through CD64 can be instrumental in developing novel intervention strategies for chronic inflammatory conditions.

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“…During the test, Western Blotting and immunohistochemistry were used for limitation and measuring the influence of specific markers. Ultimately achieving M2 macrophages resulted in a diminution in inflammatory response (Liu et al, 2013). Sica and Mantovani (2012) studied the phenotype change in macrophage property via stimulating them by IL3 and IL4.…”

Section: Discussionmentioning

confidence: 99%

Assessing the Impact of BCG Vaccine and Fertile Hydatid Cyst Fluid in Classical and Alternative Macrophage Polarization

Jalili¹,

Moslemi²,

Izadi³

et al. 2015

Research J. of Microbiology

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Classical macrophages (M1) and alternative macrophages (M2) are responsible for various functions in order to maintain homeostasis. The BCG vaccine and hydatid cyst fluid can be examples of stimulants which can cause M1 and M2 macrophage polarization. Evaluating the expression of markers such as IFNγ and TNFα for M1 phenotype and TGFβ and IL4 for M2 phenotype is one of the confirmatory ways of polarization. The purpose of this study is to verify the polarization of macrophages which was induced by BCG vaccine and hydatid cyst fluid by studying the gene expression of aforementioned markers. Mononuclear normal human peripheral blood cells were separated by using ficoll 1077 and gradient concentration. Monocyte populations were separated by adhesion technique from cultured cells in complete tissue culture medium. Monocyte derived macrophages were treated by BCG intravesical vaccine and fertile hydatid cyst fluid for 8 h. The RT-PCR was performed to confirm the polarization. The expression of amplified genes were compared with control groups. Amplification of TNFα and IFNγ genes in M1 and TGFβ and IL4 in M2 group confirmed the polarization procedure. Also, lack of PCR product in negative control samples indicates either the absence or a very low expression of this gene in control group. The ability of these stimulants in macrophage polarization can be used in experimental studies. It is also possible to take advantage of this model to achieve useful goals in cell therapy and develop more efficient therapeutic methods in inflammatory diseases and cancer immunotherapy.

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Targeting the Shift from M1 to M2 Macrophages in Experimental Autoimmune Encephalomyelitis Mice Treated with Fasudil

Cited by 183 publications

References 51 publications

Conditioned Medium from the Stem Cells of Human Exfoliated Deciduous Teeth Ameliorates Experimental Autoimmune Encephalomyelitis

Conditioned Medium from the Stem Cells of Human Exfoliated Deciduous Teeth Ameliorates Experimental Autoimmune Encephalomyelitis

Targeting CD64 mediates elimination of M1 but not M2 macrophages in vitro and in cutaneous inflammation in mice and patient biopsies

Assessing the Impact of BCG Vaccine and Fertile Hydatid Cyst Fluid in Classical and Alternative Macrophage Polarization

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