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Thrombin-induced expression of RANTES mRNA through protease activated receptor-1 in human synovial fibroblasts
  1. F Hirano,
  2. A Kobayashi,
  3. Y Hirano,
  4. Y Nomura,
  5. E Fukawa,
  6. I Makino
  1. Second Department of Internal Medicine, Asahikawa Medical College, Japan
  1. Correspondence to:
    Dr F Hirano, Second Department of Internal Medicine, Asahikawa Medical College, Midorigaoka Higashi 2–1, Asahikawa 078–8510, Japan;
    fhirano{at}asahikawa-med.ac.jp

Abstract

Objective: To examine the effects of thrombin on RANTES mRNA expression through protease activated receptor in synovial fibroblasts in patients with rheumatoid arthritis (RA).

Methods: A semiquantitative reverse transcriptase-polymerase chain reaction and reporter gene assay were performed using cultured human synovial fibroblasts from patients with RA. The up regulatory effects of thrombin on RANTES mRNA expression were tested. In addition, the roles of protease activated receptors (PARs) were analysed.

Results: PAR-1 and PAR-3, but not PAR-4, were expressed in synovial fibroblasts. Thrombin induced RANTES mRNA expression in a time dependent manner in synovial fibroblasts expressing PAR-1. A reporter gene assay showed that thrombin-induced RANTES gene expression was through PAR-1, but not PAR-3.

Conclusions: Thrombin induced RANTES mRNA expression through a PAR-1 mediated pathway, possibly indicating that thrombin has an important role in migration of inflammatory cells by RANTES to the synovium in patients with RA.

  • rheumatoid arthritis
  • RANTES
  • thrombin
  • protease activated receptor
  • FCS, fetal calf serum
  • GAPDH, glyceraldehyde-3-phosphate dehydrogenase
  • PARs, protease activated receptors
  • RA, rheumatoid arthritis
  • RANTES, regulated upon activation, normal T cells expressed and secreted
  • RT-PCR, reverse transcriptase-polymerase chain reaction

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