Expression of sphingosine kinase 2 in synovial fibroblasts of rheumatoid arthritis contributing to apoptosis by a sphingosine analogue, FTY720

Kazuo Kamada, Norimasa Arita, Takahito Tsubaki, Nobuo Takubo, Takahiro Fujino, Yoshiko Soga, Tatsuhiko Miyazaki, Haruyasu Yamamoto, Masato Nose

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Gene expression profiles in synovial tissues from rheumatoid arthritis (RA) patients have yielded useful information on the pathogenetic process of the synovitis. In one group of them, sphingosine kinase 2 (SPHK2), a nuclear protein regulating cell proliferation, seemed to be highly expressed, undergoing a different pathogenetic process of synovitis. In the present study it was clarified that SPHK2 was expressed in the synovial fibroblasts of the synovial tissues obtained from the knee joints of the RA patients. In the cultured synovial fibroblasts from these patients, SPHK2 was more highly expressed than that in the human macrophage cell line, THP-1 and human dermal fibroblasts. SPHK2 was expressed in and around the nucleus and transferred to the cytoplasm and cell surface by the administration of epidermal growth factor, associated with the increased expression of sphingosine-1-phosphate. A sphingosine analogue, FTY720, which is activated by phosphorylation specifically by SPHK2, mediated apoptotic signaling of the cultured synovial fibroblasts. These findings suggest that SPHK2 may regulate the autonomous proliferation of synovial fibroblasts as one of the predisposing genes to RA and could be a target for a novel therapeutic strategy for RA.

Original languageEnglish
Pages (from-to)382-389
Number of pages8
JournalPathology international
Volume59
Issue number6
DOIs
Publication statusPublished - 2009 Jun 1
Externally publishedYes

Keywords

  • Apoptosis
  • Early-stage rheumatoid arthritis
  • Epidermal growth factor
  • Polymerase chain reaction array
  • Sphingosine 1-phosphate

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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