title: 3H-1,2-dithiole-3-thione as a novel therapeutic agent for the treatment of experimental autoimmune encephalomyelitis.
abstract: 3H-1,2-dithiole-3-thione (D3T), the simplest member of the sulfur-containing dithiolethiones, is found in cruciferous vegetables, and has been previously reported to be a potent inducer of antioxidant genes and glutathione biosynthesis by activation of the transcription factor Nrf2. D3T is a cancer chemopreventive agent and possesses anti-inflammatory properties. Although D3T has been shown to protect against neoplasia, the effect of D3T in the autoimmune inflammatory disease multiple sclerosis/experimental autoimmune encephalomyelitis (EAE) is unknown. The present study is the first report of the therapeutic effect of D3T in EAE. Our results show D3T, administered post immunization, not only delays disease onset but also dramatically reduces disease severity in EAE. Strikingly, D3T, administered post disease onset of EAE, effectively prevents disease progression and exacerbation. Mechanistic studies revealed that D3T suppresses dendritic cell activation and cytokine production, inhibits pathogenic Th1 and Th17 differentiation, represses microglia activation and inflammatory cytokine expression, and promotes microglia phase II enzyme induction. In summary, these results indicate that D3T affects both innate and adaptive immune cells, and the protective effect of D3T in EAE might be attributed to its effects on modulating dendritic cell and microglia activation and pathogenic Th1/Th17 cell differentiation.
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Fort Wayne, IN, United States.
authors.forename: Ping-Chang
authors.initials: PC
authors.lastname: Kuo
authors.affiliation: Department of Pharmaceutical Sciences, Manchester University College of Pharmacy, Fort Wayne, IN, United States.
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Brown
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Fort Wayne, IN, United States.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Scofield
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, Fort Wayne, IN, United States.
authors.forename: I-Chen
authors.initials: IC
authors.lastname: Yu
authors.affiliation: Department of Neurology, Indiana University School of Medicine, Fort Wayne, IN, United States.
authors.forename: Fen-Lei
authors.initials: FL
authors.lastname: Chang
authors.affiliation: Graduate Institute of Brain and Mind Science, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Fort Wayne, IN, United States. Electronic address: yenj@ipfw.edu.
authors.forename: Jui-Hung
authors.initials: JH
authors.lastname: Yen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects*; D018417:Th1 Cells / Q000187:drug effects*; D058504:Th17 Cells / Q000187:drug effects*; D013871:Thiones / Q000008:administration & dosage / Q000494:pharmacology*; D013876:Thiophenes / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D013871:Thiones; D013876:Thiophenes; C049325:1,2-dithiol-3-thione
keywords: D3T; Dendritic cells; MS/EAE; Microglia; Th1/Th17