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Title

A cannabigerol derivative suppresses immune responses and protects mice from experimental autoimmune encephalomyelitis

AuthorsCarrillo-Salinas, F. J.; Navarrete, Carmen; Mecha, Miriam ; Feliú, Ana; Collado, J.A.; Cantarero, Irene; Bellido, María Luz ; Muñoz, E.; Guaza, Carmen
KeywordsExperimental autoimmune
Issue Date2014
PublisherPublic Library of Science
CitationPLoS ONE 9 (2014)
AbstractPhytocannabinoids that do not produce psychotropic effects are considered of special interest as novel therapeutic agents in CNS diseases. A cannabigerol quinone, the compound VCE-003, has been shown to alleviate symptoms in a viral model of multiple sclerosis (MS). Hence, we studied T cells and macrophages as targets for VCE-003 and its efficacy in an autoimmune model of MS. Proliferation, cell cycle, expression of activation markers was assessed by FACs in human primary T cells, and cytokine and chemokine production was evaluated. Transcription was studied in Jurkat cells and RAW264.7 cells were used to study the effects of VCE-003 on IL-17-induced macrophage polarization to a M1 phenotype. Experimental autoimmune encephalomyelitis (EAE) was induced by myelin oligodendrocyte glycoprotein (MOG35-55) immunization and spinal cord pathology was assessed by immunohistochemistry. Neurological impairment was evaluated using disease scores. We show here that VCE-003 inhibits CD3/CD28-induced proliferation, cell cycle progression and the expression of the IL-2Ra and ICAM-1 activation markers in human primary T cells. VCE-003 inhibits the secretion of Th1/Th17 cytokines and chemokines in primary murine T cells, and it reduces the transcriptional activity of the IL-2, IL-17 and TNFa promoters induced by CD3/ CD28. In addition, VCE-003 and JWH-133, a selective CB2 agonist, dampened the IL-17-induced polarization of macrophages to a pro-inflammatory M1 profile. VCE-003 also prevented LPS-induced iNOS expression in microglia. VCE-003 ameliorates the neurological defects and the severity of MOG-induced EAE in mice through CB2 and PPARc receptor activation. A reduction in cell infiltrates, mainly CD4T cells, was observed, and Th1 and Th17 responses were inhibited in the spinal cord of VCE-003-treated mice, accompanied by weaker microglial activation, structural preservation of myelin sheets and reduced axonal damage. This study highlights the therapeutic potential of VCE-003 as an agent for the treatment of human immune diseases with both inflammatory and autoimmune components. © 2014 Carrillo-Salinas et al.
URIhttp://hdl.handle.net/10261/156411
DOI10.1371/journal.pone.0094733
Identifiersdoi: 10.1371/journal.pone.0094733
issn: 1932-6203
Appears in Collections:(IC) Artículos
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