title: Dimethyl fumarate suppresses Theiler's murine encephalomyelitis virus-induced demyelinating disease by modifying the Nrf2-Keap1 pathway.
abstract: Dimethyl fumarate (DMF) is a modifier of the nuclear factor (erythroid-derived 2)-2 (Nrf2)-kelch-like ECH-associated protein 1 (Keap1) pathway. DMF treatment in the effector phase significantly suppressed the development of Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) both clinically and histologically. DMF treatment leads to an enhanced Nrf2 antioxidant response in TMEV-IDD mice. DMF treatment in the effector phase significantly suppressed the level of IL-17A mRNA. DMF is known to inhibit differentiation of T helper 17 (Th17) cells via suppressing NF-κB. Taken together, our data suggest that DMF treatment in the effector phase may suppress TMEV-IDD not only via enhancing the antioxidant response but also via suppressing IL-17A.
authors.affiliation: Department of Biomedical Laboratory Sciences, Graduate School of Medicine, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Kunitoshi
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Biomedical Laboratory Sciences, Graduate School of Medicine, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tomiki
authors.affiliation: Department of Pediatrics, School of Medicine, Shinshu University, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Inaba
authors.affiliation: Department of Biomedical Laboratory Sciences, Graduate School of Medicine, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Motoki
authors.initials: M
authors.lastname: Ichikawa
authors.affiliation: Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA.
authors.forename: Byung S
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Department of Biomedical Laboratory Sciences, Graduate School of Medicine, Matsumoto, Nagano 390-8621, Japan kshosei@shinshu-u.ac.jp.
authors.forename: Chang-Sung
authors.initials: CS
authors.lastname: Koh
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003711:Demyelinating Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D000069462:Dimethyl Fumarate / Q000494:pharmacology*; D005260:Female; D000072019:Kelch-Like ECH-Associated Protein 1; D051379:Mice; D008815:Mice, Inbred Strains; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D017945:Theilovirus / Q000187:drug effects*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C117301:Keap1 protein, mouse; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; D000069462:Dimethyl Fumarate
keywords: Nrf2-Keap1 pathway; TMEV-induced demyelinating disease (TMEV-IDD); Theiler’s murine encephalomyelitis virus (TMEV); dimethyl fumarate (DMF); multiple sclerosis (MS)