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dc.contributor.authorGómez-Pérez, R
dc.contributor.authorRedondo, M
dc.contributor.authorMartínez, A
dc.contributor.authorGil, C
dc.contributor.authorGonzalez, Carlos 
dc.contributor.authorBravo, Beatriz 
dc.contributor.authorBallester, Alicia 
dc.contributor.authorEguiluz, Cesar 
dc.contributor.authorBallester, Sara
dc.identifier.citationBr J Pharmacol . 2013 Oct;170(3):602-13.es_ES
dc.description.abstractPDE4 inhibition suppresses experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). However, side effects hinder PDE4 inhibitors clinical use. PDE7 inhibition might constitute an alternative therapeutic strategy, but few data about the anti-inflammatory potential of PDE7 inhibitors are currently available. We have used the EAE model to perform a comparative evaluation of PDE4 and PDE7 inhibition as strategies for MS treatment. Two PDE7 inhibitors, the sulfonamide derivative BRL50481 and the recently described quinazoline compound TC3.6, were assayed to modulate EAE in SJL mice, in comparison with the well-known PDE4 inhibitor Rolipram. We evaluated clinical signs, presence of inflammatory infiltrates in CNS and anti-inflammatory markers. We also analysed the effect of these inhibitors on the inflammatory profile of spleen cells in vitro. TC3.6 prevented EAE with efficacy similar to Rolipram, while BRL50481 had no effect on the disease. Differences between both PDE7 inhibitors are discussed. Data from Rolipram and TC3.6 showed that PDE4 and PDE7 inhibition work through both common and distinct pathways. Rolipram administration caused an increase in IL-10 and IL-27 expression which was not found after TC3.6 treatment. On the other hand, both inhibitors reduced IL-17 levels, prevented infiltration in CNS and increased the expression of the T regulator cell marker Foxp3. These results provide new information about the effects of Rolipram on EAE, underline PDE7 inhibition as a new therapeutic target for inflammatory diseases and show the value of TC3.6 to prevent EAE, with possible consequences for new therapeutic tools in MS.es_ES
dc.description.sponsorshipThis work was sponsored by grants from Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica, Acción estratégica en Salud (PS09/00604 and SAF2009-13015-C02-01) and Instituto de Salud Carlos III (MPY 1402/0909 and RD07/0060/0015). R.G-P was supported by a grant from Instituto de Salud Carlos III. Authors are grateful to F. Javier Hernández and Marta Blanco for the valuable technical assistance. Authors also wish to thank Dr. R. Murillas for the critical reading of the manuscript.es_ES
dc.publisherWiley es_ES
dc.subject.meshAnimals es_ES
dc.subject.meshAnti-Inflammatory Agents es_ES
dc.subject.meshBrain es_ES
dc.subject.meshCells, Cultured es_ES
dc.subject.meshCyclic Nucleotide Phosphodiesterases, Type 4es_ES
dc.subject.meshCyclic Nucleotide Phosphodiesterases, Type 7 es_ES
dc.subject.meshEncephalomyelitis, Autoimmune, Experimental es_ES
dc.subject.meshForkhead Transcription Factors es_ES
dc.subject.meshInflammation Mediators es_ES
dc.subject.meshInterleukin-10 es_ES
dc.subject.meshInterleukin-17 es_ES
dc.subject.meshInterleukins es_ES
dc.subject.meshMice es_ES
dc.subject.meshMice, Inbred C57BL es_ES
dc.subject.meshPhosphodiesterase 4 Inhibitors es_ES
dc.subject.meshRolipram es_ES
dc.subject.meshSpleen es_ES
dc.subject.meshT-Lymphocytes, Regulatory es_ES
dc.titleComparative assessment of PDE 4 and 7 inhibitors as therapeutic agents in experimental autoimmune encephalomyelitis.es_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.contributor.funderUnión Europea 
dc.contributor.funderEuropean Molecular Biology Organization 
dc.contributor.funderInstituto de Salud Carlos III 
dc.identifier.journalBritish journal of pharmacologyes_ES
dc.repisalud.centroISCIII::Unidad Funcional de Investigación de Enfermedades Crónicas (UFIEC)es_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiología
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/MPY 1402/0909es_ES
dc.rights.accessRightsopen accesses_ES

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Atribución-NoComercial-CompartirIgual 4.0 Internacional
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