The ribosomal S6 kinase inhibitor BI-D1870 ameliorated experimental autoimmune encephalomyelitis in mice

Ichiro Takada; Yoshiko Yogiashi; Makoto Makishima

doi:10.1016/j.imbio.2015.09.008

The ribosomal S6 kinase inhibitor BI-D1870 ameliorated experimental autoimmune encephalomyelitis in mice

Immunobiology. 2016 Feb;221(2):188-92. doi: 10.1016/j.imbio.2015.09.008. Epub 2015 Sep 8.

Authors

Ichiro Takada¹, Yoshiko Yogiashi², Makoto Makishima³

Affiliations

¹ 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.
² School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan.
³ Division of Biochemistry, Department of Biomedical Sciences, School of Medicine, Nihon University, Itabashi-ku, Tokyo 173-8610, Japan.

PMID: 26386981
DOI: 10.1016/j.imbio.2015.09.008

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.

Keywords: RORgt; RSK; Th17 cell.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Movement / drug effects
Central Nervous System / drug effects
Central Nervous System / immunology
Central Nervous System / pathology
Disease Models, Animal
Encephalomyelitis, Autoimmune, Experimental / chemically induced
Encephalomyelitis, Autoimmune, Experimental / drug therapy*
Encephalomyelitis, Autoimmune, Experimental / genetics
Encephalomyelitis, Autoimmune, Experimental / immunology
Gene Expression Regulation
Mice
Mice, Inbred C57BL
Multiple Sclerosis / genetics
Multiple Sclerosis / immunology
Multiple Sclerosis / pathology
Myelin-Oligodendrocyte Glycoprotein
Peptide Fragments
Protein Kinase Inhibitors / pharmacology*
Pteridines / pharmacology*
RNA, Messenger / antagonists & inhibitors
RNA, Messenger / genetics
RNA, Messenger / immunology
Receptors, CCR6 / antagonists & inhibitors
Receptors, CCR6 / genetics
Receptors, CCR6 / immunology
Ribosomal Protein S6 Kinases, 90-kDa / antagonists & inhibitors*
Ribosomal Protein S6 Kinases, 90-kDa / genetics
Ribosomal Protein S6 Kinases, 90-kDa / immunology
Signal Transduction
Th1 Cells / drug effects*
Th1 Cells / immunology
Th1 Cells / pathology
Th17 Cells / drug effects*
Th17 Cells / immunology
Th17 Cells / pathology

Substances

BI D1870
CCR6 protein, mouse
Myelin-Oligodendrocyte Glycoprotein
Peptide Fragments
Protein Kinase Inhibitors
Pteridines
RNA, Messenger
Receptors, CCR6
myelin oligodendrocyte glycoprotein (35-55)
Ribosomal Protein S6 Kinases, 90-kDa
ribosomal protein S6 kinase, 90kDa, polypeptide 3