TY - JOUR
T1 - A novel sphingosine-1-phosphate receptor agonist KRP-203 attenuates rat autoimmune myocarditis
AU - Ogawa, Ryo
AU - Takahashi, Masafumi
AU - Hirose, Sho ichi
AU - Morimoto, Hajime
AU - Ise, Hirohiko
AU - Murakami, Takashi
AU - Yasue, Tokutaro
AU - Kuriyama, Kazuhiko
AU - Hongo, Minoru
AU - Kobayashi, Eiji
AU - Ikeda, Uichi
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2007/9/28
Y1 - 2007/9/28
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bbrc.2007.07.061
DO - 10.1016/j.bbrc.2007.07.061
M3 - Article
C2 - 17673173
AN - SCOPUS:34547756416
SN - 0006-291X
VL - 361
SP - 621
EP - 628
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -
