Harunori Takeshita

Publications (2)2.48 Total impact

• Article: Sphingosine 1-phosphate (S1P)/S1P receptor 1 signaling regulates receptor activator of NF-κB ligand (RANKL) expression in rheumatoid arthritis.

  Harunori Takeshita, Masayasu Kitano, Tsuyoshi Iwasaki, Sachie Kitano, Sachi Tsunemi, Chieri Sato, Masahiro Sekiguchi, Naoto Azuma, Keiji Miyazawa, Timothy Hla, Hajime Sano
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  ABSTRACT: Sphingosine 1-phosphate (S1P)/S1P receptor 1 (S1P1) signaling plays an important role in synovial cell proliferation and inflammatory gene expression by rheumatoid arthritis (RA) synoviocytes. The purpose of this study is to clarify the role of S1P/S1P1 signaling in the expression of receptor activator of NF-κB ligand (RANKL) in RA synoviocytes and CD4(+) T cells. We demonstrated MH7A cells, a human RA synovial cell line, and CD4(+) T cells expressed S1P1 and RANKL. Surprisingly, S1P increased RANKL expression in MH7A cells and CD4(+) T cells in a dose-dependent manner. Moreover, S1P enhanced RANKL expression induced by stimulation with TNF-α in MH7A cells and CD4(+) T cells. These effects of S1P in MH7A cells were inhibited by pretreatment with PTX, a specific Gi/Go inhibitor. These findings suggest that S1P/S1P1 signaling may play an important role in RANKL expression by MH7A cells and CD4(+) T cells. S1P/S1P1 signaling of RA synoviocytes is closely connected with synovial hyperplasia, inflammation, and RANKL-induced osteoclastogenesis in RA. Thus, regulation of S1P/S1P1 signaling may become a novel therapeutic target for RA.
  Biochemical and Biophysical Research Communications 02/2012; 419(2):154-9. · 2.48 Impact Factor
• Source

  Available from: Tsuyoshi Iwasaki

  Article: Therapy of autoimmune diseases by novel immunosuppressant FTY720

  Sachi Tsunemi, Tsuyoshi Iwasaki, Keiji Miyazawa, Sachie Kitano, Chieri Kanda, Harunori Takeshita, Masahiro Sekiguchi, Masayasu Kitano, Hajime Sano
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  ABSTRACT: FTY720 (FTY) is a new immunosuppressant which modulates sphingosine 1-phospate re-ceptors. FTY has been shown to be highly effective to multiple sclerosis in clinical studies. Recently, we reported the effects and the mechanisms by which FTY inhibited arthritis in rheumatoid arthritis model of SKG mice. Here, we briefly review up to date reports of FTY including our experimental results.
  Inflammation and Regeneration 04/2011; 31.