title: The ribosomal S6 kinase inhibitor BI-D1870 ameliorated experimental autoimmune encephalomyelitis in mice.
abstract: Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS) caused by the infiltration of TH1 and TH17 cells into the CNS. Ribosomal S6 kinase 2 (RSK2; RPS6KA3) regulates TH17 differentiation by attenuating RORγt transcriptional activities and IL-17A production. The pan-RSK inhibitor BI-D1870 also inhibits TH17 differentiation, but the effect of BI-D1870 in vivo remains unclear. Here, we generated mice with experimental autoimmune encephalomyelitis (EAE) and treated them with BI-D1870. BI-D1870 administration protected mice from EAE by reducing the infiltration of TH1 and TH17 cells into the CNS and decreasing mRNA levels of Ccr6 in TH17 cells. These results suggest that RSK inhibition is a promising strategy for the treatment of MS.
authors.affiliation: Division of Biochemistry, Department of Biomedical Sciences, School of Medicine, Nihon University, Itabashi-ku, Tokyo 173-8610, Japan; School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan. Electronic address: takada.ichiro@nihon-u.ac.jp.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takada
authors.affiliation: School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Yogiashi
authors.affiliation: Division of Biochemistry, Department of Biomedical Sciences, School of Medicine, Nihon University, Itabashi-ku, Tokyo 173-8610, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Makishima
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011621:Pteridines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D054399:Receptors, CCR6 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
chemical_list: C516541:BI D1870; C498126:CCR6 protein, mouse; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D047428:Protein Kinase Inhibitors; D011621:Pteridines; D012333:RNA, Messenger; D054399:Receptors, CCR6; C445081:myelin oligodendrocyte glycoprotein (35-55); D038744:Ribosomal Protein S6 Kinases, 90-kDa; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3
keywords: RORgt; RSK; Th17 cell