3H-1,2-dithiole-3-thione as a novel therapeutic agent for the treatment of experimental autoimmune encephalomyelitis

Ping Chang Kuo, Dennis A. Brown, Barbara A. Scofield, I. Chen Yu, Fen-Lei Chang, Pei Yu Wang, Jui Hung Yen

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)173-186
Number of pages14
JournalBrain, Behavior, and Immunity
Volume57
DOIs
StatePublished - Oct 1 2016

Fingerprint

Thiones
Autoimmune Experimental Encephalomyelitis
Microglia
Therapeutics
Dendritic Cells
Disease Progression
Cytokines
1,2-dithiol-3-thione
Th17 Cells
Th1 Cells
Enzyme Induction
Therapeutic Uses
Sulfur
Vegetables
Autoimmune Diseases
Multiple Sclerosis
Glutathione
Cell Differentiation
Immunization
Neoplasms

Keywords

  • D3T
  • Dendritic cells
  • Microglia
  • MS/EAE
  • Th1/Th17

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

Cite this

3H-1,2-dithiole-3-thione as a novel therapeutic agent for the treatment of experimental autoimmune encephalomyelitis. / Kuo, Ping Chang; Brown, Dennis A.; Scofield, Barbara A.; Yu, I. Chen; Chang, Fen-Lei; Wang, Pei Yu; Yen, Jui Hung.

In: Brain, Behavior, and Immunity, Vol. 57, 01.10.2016, p. 173-186.

Research output: Contribution to journalArticle

Kuo, Ping Chang ; Brown, Dennis A. ; Scofield, Barbara A. ; Yu, I. Chen ; Chang, Fen-Lei ; Wang, Pei Yu ; Yen, Jui Hung. / 3H-1,2-dithiole-3-thione as a novel therapeutic agent for the treatment of experimental autoimmune encephalomyelitis. In: Brain, Behavior, and Immunity. 2016 ; Vol. 57. pp. 173-186.
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