A novel sphingosine-1-phosphate receptor agonist KRP-203 attenuates rat autoimmune myocarditis

Ryo Ogawa, Masafumi Takahashi, Sho ichi Hirose, Hajime Morimoto, Hirohiko Ise, Takashi Murakami, Tokutaro Yasue, Kazuhiko Kuriyama, Minoru Hongo, Eiji Kobayashi, Uichi Ikeda

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Sphingosine-1-phosphate (S1P) is an active sphingolipid metabolite that exerts important biological effects. Recently, we demonstrated that KRP-203 is a novel S1P receptor agonist that can alter lymphocyte homing and act as an immunomodulating agent. We investigated the efficacy of KRP-203 in the treatment of rat experimental autoimmune myocarditis. KRP-203 significantly attenuated the inflammation area, heart weight/body weight ratio, and left ventricular function. Immunohistochemical analysis and RT-PCR revealed that KRP-203 significantly decreased the infiltration of macrophages and CD4 T cells in the myocardium and the expression of inflammatory cytokines. Flow cytometric analysis revealed that treatment with KRP-203 effectively reduced the number of peripheral CD4 and CD8 T cells but not that of B cells and granulocytes. Further, late KRP-203 treatment was effective even against established EAM. These results demonstrate the therapeutic potential of KRP-203 for the treatment of human myocarditis and provide new insights into the pathogenesis of this disease.

Original languageEnglish
Pages (from-to)621-628
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume361
Issue number3
DOIs
Publication statusPublished - Sep 28 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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