Dithiolethione ACDT suppresses neuroinflammation and ameliorates disease severity in experimental autoimmune encephalomyelitis

dc.contributor.authorKuo, Ping-Chang
dc.contributor.authorBrown, Dennis A.
dc.contributor.authorScofield, Barbara A.
dc.contributor.authorParaiso, Hallel C.
dc.contributor.authorWang, Pei-Yu
dc.contributor.authorYu, I-Chen
dc.contributor.authorYen, Jui-Hung
dc.contributor.departmentMicrobiology and Immunology, School of Medicineen_US
dc.date.accessioned2018-04-24T15:55:25Z
dc.date.available2018-04-24T15:55:25Z
dc.date.issued2018
dc.description.abstractMultiple sclerosis (MS) is an autoimmune disorder characterized by the central nervous system (CNS) infiltration of myelin-specific pathogenic T cells followed by brain inflammation in association with demyelination. Similarly, experimental autoimmune encephalomyelitis (EAE), the animal model of MS, also exhibits increased CNS infiltration of pathogenic T cells, including Th1 and Th17, leading to detrimental effects of neuroinflammation and demyelination. We previously reported that 3H-1,2-dithiole-3-thione (D3T), the structurally-simplest of the sulfur-containing dithiolethiones, exerted a promising therapeutic effect in EAE. In the current study we report that 5-Amino-3-thioxo-3H-(1,2)dithiole-4-carboxylic acid ethyl ester (ACDT), a substituted derivative of D3T, exhibits anti-inflammatory properties in EAE. ACDT, administered post immunization, delayed disease onset and reduced disease severity in chronic C57BL/6 EAE, and ACDT, administered during disease remission, suppressed disease relapse in relapsing-remitting SJL/J EAE. Further analysis of the cellular and molecular mechanisms underlying the protective effects of ACDT in EAE revealed that ACDT inhibited pathogenic T cell infiltration, suppressed microglia activation, repressed neurotoxic A1 astrocyte generation, lessened blood-brain barrier disruption, and diminished MMP3/9 production in the CNS of EAE. In summary, we demonstrate that ACDT suppresses neuroinflammation and ameliorates disease severity in EAE through multiple cellular mechanisms. Our findings suggest the potential of developing ACDT as a novel therapeutic agent for the treatment of MS/EAE.en_US
dc.eprint.versionAuthor's manuscripten_US
dc.identifier.citationKuo, P.-C., Brown, D. A., Scofield, B. A., Paraiso, H. C., Wang, P.-Y., Yu, I.-C., & Yen, J.-H. (2018). Dithiolethione ACDT suppresses neuroinflammation and ameliorates disease severity in experimental autoimmune encephalomyelitis. Brain, Behavior, and Immunity. https://doi.org/10.1016/j.bbi.2018.03.010en_US
dc.identifier.urihttps://hdl.handle.net/1805/15898
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.isversionof10.1016/j.bbi.2018.03.010en_US
dc.relation.journalBrain, Behavior, and Immunityen_US
dc.rightsPublisher Policyen_US
dc.sourceAuthoren_US
dc.subjectMS/EAEen_US
dc.subjectmicrogliaen_US
dc.subjectTh1/Th17en_US
dc.titleDithiolethione ACDT suppresses neuroinflammation and ameliorates disease severity in experimental autoimmune encephalomyelitisen_US
dc.typeArticleen_US
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