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Title

The endocannabinoid anandamide downregulates IL-23 and IL-12 subunits in a viral model of multiple sclerosis: Evidence for a cross-talk between IL-12p70/IL-23 axis and IL-10 in microglial cells

AuthorsCorrea, Fernando Gabriel ; Hernangómez-Herrero, Miriam ; Mestre, Leyre ; Loría, Frida ; Docagne, Fabian ; Guaza, Carmen
KeywordsTMEV
Multiple sclerosis
Endocannabinoids
Anandamide
Microglia
IL-12p70
IL-23
IL-10
Issue DateMay-2011
PublisherAcademic Press
CitationBrain, Behavior, and Immunity 25(4): 736-749 (2011)
AbstractTheiler's virus (TMEV) infection of the central nervous system (CNS) induces an immune-mediated demyelinating disease in susceptible mouse strains and serves as a relevant infection model for human multiple sclerosis (MS). The endocannabinoid system represents a novel therapeutic target for autoimmune and chronic inflammatory diseases due to its anti-inflammatory properties by regulating cytokine network. IL-12p70 and IL-23 are functionally related heterodimeric cytokines that play a crucial role in the pathogenesis of MS. In the present study we showed that the endocannabinoid anandamide (AEA) downregulated the gene expression of IL-12p70 and IL-23 forming subunits mRNAs in the spinal cord of TMEV-infected mice and ameliorated motor disturbances. This was accompanied by significant decreases on the serological levels of IL-12p70/IL-23 and more interestingly, of IL-17A. In contrast, serum levels of IL-10 resulted elevated. In addition, we studied the signalling pathways involved in the regulation of IL-12p70/IL-23 and IL-10 expression in TMEV-infected microglia and addressed the possible interactions of AEA with these pathways. AEA acted through the ERK1/2 and JNK pathways to downregulate IL-12p70 and IL-23 while upregulating IL-10. These effects were partially mediated by CB2 receptor activation. We also described an autocrine circuit of cross-talk between IL-12p70/IL-23 and IL-10, since endogenously produced IL-10 negatively regulates IL-12p70 and IL-23 cytokines in TMEV-infected microglia. This suggests that by altering the cytokine network, AEA could indirectly modify the type of immune responses within the CNS. Accordingly, pharmacological modulation of endocannabinoids might be a useful tool for treating neuroinflammatory diseases. © 2011 Elsevier Inc.
Publisher version (URL)http://doi.org/10.1016/j.bbi.2011.01.020
URIhttp://hdl.handle.net/10261/66392
DOI10.1016/j.bbi.2011.01.020
Identifiersdoi: 10.1016/j.bbi.2011.01.020
issn: 0889-1591
Appears in Collections:(IC) Artículos
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