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dc.creatorMiljković, Đorđe
dc.creatorBlaževski, Jana
dc.creatorPetković, Filip
dc.creatorĐedović, Neda
dc.creatorMomčilović, Miljana B.
dc.creatorStanisavljević, Suzana
dc.creatorJevtić, Bojan
dc.creatorStojkovic, Marija Mostarica
dc.creatorSpasojevic, Ivan
dc.date.accessioned2016-05-23T10:59:50Z
dc.date.issued2015
dc.identifier.issn1550-6606
dc.identifier.urihttps://ibiss-r.rcub.bg.ac.rs/handle/123456789/1987
dc.description.abstractDimethyl fumarate (DMF), a new drug for multiple sclerosis (MS) treatment, acts against neuroinflammation via mechanisms that are triggered by adduct formation with thiol redox switches. Ethyl pyruvate (EP), an off-the-shelf agent, appears to be a redox analog of DMF, but its immunomodulatory properties have not been put into the context of MS therapy. In this article, we examined and compared the effects of EP and DMF on MS-relevant activity/functions of T cells, macrophages, microglia, and astrocytes. EP efficiently suppressed the release of MS signature cytokines, IFN-gamma and IL-17, from human PBMCs. Furthermore, the production of these cytokines was notably decreased in encephalitogenic T cells after in vivo application of EP to rats. Production of two other proinflammatory cytokines, IL-6 and TNF, and NO was suppressed by EP in macrophages and microglia. Reactive oxygen species production in macrophages, microglia activation, and the development of Ag-presenting phenotype in microglia and macrophages were constrained by EP. The release of IL-6 was reduced in astrocytes. Finally, EP inhibited the activation of transcription factor NF-kappa B in microglia and astrocytes. Most of these effects were also found for DMF, implying that EP and DMF share common targets and mechanisms of action. Importantly, EP had in vivo impact on experimental autoimmune encephalomyelitis, an animal model of MS. Treatment with EP resulted in delay and shortening of the first relapse, and lower clinical scores, whereas the second attack was annihilated. Further studies on the possibility to use EP as an MS therapeutic are warranted.
dc.description.sponsorshipMinistry of Education, Science and Technological Development of the Republic of Serbia {[}OI173035, OI175038, OI173014, OI173013]
dc.languageEnglish
dc.rightsrestrictedAccess
dc.sourceJournal of Immunology
dc.titleA Comparative Analysis of Multiple Sclerosis-Relevant Anti-Inflammatory Properties of Ethyl Pyruvate and Dimethyl Fumarate
dc.typearticle
dc.rights.licenseARR
dcterms.abstractЂедовић, Неда; Спасојевиц, Иван; Стојковиц, Марија Мостарица; Блажевски, Јана; Јевтић, Бојан; Миљковић, Ђорђе М.; Петковић, Филип; Момчиловић, Миљана Б.; Станисављевић, Сузана;
dc.citation.issue6
dc.citation.volume194
dc.identifier.doi10.4049/jimmunol.1402302
dc.identifier.scopus2-s2.0-84924530072
dc.identifier.wos000350755200008
dc.citation.spage2493
dc.citation.epage2503
dc.type.versionpublishedVersionen


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