TITLE

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

AUTHOR(S)
Liu, Chunyun; Li, Yanhua; Yu, Jiezhong; Feng, Ling; Hou, Shaowei; Liu, Yueting; Guo, Mingfang; Xie, Yong; Meng, Jian; Zhang, Haifei; Xiao, Baoguo; Ma, Cungen
PUB. DATE
February 2013
SOURCE
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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.
ACCESSION #
87623528

 

Related Articles

  • Long-term persistence after acute Q fever of non-infective Coxiella burnetii cell components, including antigens*. Sukocheva, O.A.; Marmion, B.P.; Storm, P.A.; Lockhart, M.; Turra, M.; Graves, S. // QJM: An International Journal of Medicine;Nov2010, Vol. 103 Issue 11, p847 

    Background: Previous studies of inciting factors for a prolonged post-infection fatigue syndrome after Q fever (variously termed QFS or Q fever associated CFS/ME in the literature) showed that after the acute infection a high proportion of asymptomatic and QFS patients had Q fever antibody and...

  • Microglia and monocytes: 'tis plain the twain meet in the brain. Ransohoff, Richard M. // Nature Neuroscience;Sep2011, Vol. 14 Issue 9, p1098 

    The article presents a study on the involvement of microglia and monocytes on the development of multiple sclerosis based on the mouse model, the experimental autoimmune encephalomyelitis (EAE). It notes that the findings reveal that macrophages involved in acute inflammatory central nervous...

  • Strain-related effects of fenbendazole treatment on murine experimental autoimmune encephalomyelitis. Ramp, A. A.; Hall, C.; Orian, J. M. // Laboratory Animals;Jul2010, Vol. 44 Issue 3, p271 

    Parasitic infections are a concern in animal facilities, in view of their influence on physiological processes and the immune status of animals. Pinworms are effectively controlled with the anthelminthic fenbendazole (FBZ, [5-(phenylthio)-1Hbenzamidazol- 2-yl]carbamic acid methyl ester;...

  • Peli1 sets the CNS on fire. Song, Xinyang; Qian, Youcun // Nature Medicine;May2013, Vol. 19 Issue 5, p536 

    The article offers information on the E3 ubiquitin ligase Peli1 which was identified as an important regulator of microglia activation during the pathogenesis of experimental autoimmune encephalomyelitis (EAE). It says that the essential role of Peli1 was recognized by using mouse model of human...

  • Essential Role of NK Cells in IgG Therapy for Experimental Autoimmune Encephalomyelitis. Chong, Wai Po; Ling, Man To; Liu, Yinping; Caspi, Rachel R.; Wong, Wai Man; Wu, Wutian; Tu, Wenwei; Lau, Yu Lung // PLoS ONE;Apr2013, Vol. 8 Issue 4, p1 

    Intravenous immunoglobulin has long been used in treating autoimmune diseases, although mechanisms remain uncertain. Activating Fcγ receptors are receptors of IgG and reported to be essential in intravenous immunoglobulin (IVIG) therapy. Therefore, we hypothesized natural killer (NK) cells,...

  • Selective Chemokine Receptor Usage by Central Nervous System Myeloid Cells in CCR2-Red Fluorescent Protein Knock-In Mice. Saederup, Noah; Cardona, Astrid E.; Croft, Kelsey; Mizutani, Makiko; Cotleur, Anne C.; Chia-Lin Tsou; Ransohoff, Richard M.; Charo, Israel F. // PLoS ONE;2010, Vol. 5 Issue 10, p1 

    Background: Monocyte subpopulations distinguished by differential expression of chemokine receptors CCR2 and CX3CR1 are difficult to track in vivo, partly due to lack of CCR2 reagents. Methodology/Principal Findings: We created CCR2-red fluorescent protein (RFP) knock-in mice and crossed them...

  • Disparate Effects of Mesenchymal Stem Cells in Experimental Autoimmune Encephalomyelitis and Cuprizone-Induced Demyelination. Glenn, Justin D.; Smith, Matthew D.; Kirby, Leslie A.; Baxi, Emily G.; Whartenby, Katharine A // PLoS ONE;9/25/2015, Vol. 10 Issue 9, p1 

    Mesenchymal stem cells (MSCs) are pleiotropic cells with potential therapeutic benefits for a wide range of diseases. Because of their immunomodulatory properties they have been utilized to treat autoimmune diseases such as multiple sclerosis (MS), which is characterized by demyelination. The...

  • Physiological Induction of Regulatory Qa-1-Restricted CD8+ T Cells Triggered by Endogenous CD4+ T Cell Responses. Varthaman, Aditi; Clement, Marc; Khallou-Laschet, Jamila; Fornasa, Giulia; Gaston, Anh-Thu; Dussiot, Michael; Caligiuri, Giuseppina; Cantor, Harvey; Kaveri, Srinivas; Nicoletti, Antonino // PLoS ONE;2011, Vol. 6 Issue 6, p1 

    T cell-dependent autoimmune diseases are characterized by the expansion of T cell clones that recognize immunodominant epitopes on the target antigen. As a consequence, for a given autoimmune disorder, pathogenic T cell clones express T cell receptors with a limited number of variable regions...

  • Interleukin-25 inhibits interleukin-12 production and Th1 cell-driven inflammation in the gut.  // Inflammatory Bowel Disease Monitor;Apr2009, Vol. 10 Issue 2, p67 

    The article discusses, evidence that the interleukin-25 breaks the secretion by CD 14+ monocytes of IL-23 and IL-12 from patients and mice. The authors offer insights regarding the procedure of the study and the process of the experiment. Result shows that there was a therapeutic effect in the...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics