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Ann Rheum Dis 1999;58:55-60 doi:10.1136/ard.58.1.55
  • Extended reports

Thrombin receptor mediated signals induce expressions of interleukin 6 and granulocyte colony stimulating factor via NF-κB activation in synovial fibroblasts

  1. Hiroshi Shina,b,
  2. Isao Kitajimab,
  3. Toshihiro Nakajimab,c,
  4. Qing Shaob,
  5. Takeshi Tokiokab,
  6. Ikuko Takasakib,
  7. Naohiro Hanyub,
  8. Toshikazu Kubod,
  9. Ikuro Maruyamab
  1. aDrug Discovery Research Laboratories, Kaken Pharmaceutical Co, Ltd, Kyoto, Japan, bDepartments of Laboratory and Molecular Medicine Kagoshima University, Kagoshima, Japan, cInstitute of Applied Biochemistry, Tsukuba University, Ibaraki, Japan, dDepartment of Orthopaedic Surgery, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Japan
  1. Dr I Kitajima, Department of Laboratory and Molecular Medicine, Kagoshima University School of Medicine, 8–35–1 Sakuragaoka, Kagoshima 890-8250, Japan.
  • Accepted 23 September 1998

Abstract

OBJECTIVE To clarify the mechanism of thrombin receptor mediated signal transduction and the induction of cytokines by thrombin stimulation in rheumatoid synovial fibroblasts.

METHODS Cytokines were measured by enzyme linked immunosorbent assay (ELISA) in the supernatants of cultured rheumatoid synovial fibroblasts stimulated by thrombin. To assess the mechanism of thrombin receptor mediated signal transduction in the rheumatoid synovial fibroblasts, electrophoretic mobility gel shift assay (EMSA), immunoglobulin κ-chloramphenicol acetyltransferase (CAT) assay, and immunostaining for NF-κB subunit molecule was performed.

RESULTS Thrombin stimulation activated the inducible transcription factor NF-κB, and then induced subsequent expressions of interleukin 6 (IL6) and granulocyte colony stimulating factor (G-CSF) in the cells.

CONCLUSION Thrombin receptor mediated signal transduction could induce the expressions of IL6 and G-CSF, and increase inflammatory events in the cavum articulare via NF-κB activation.

Footnotes

  • Funding: this work was supported by a Ministry of Education grant for general scientific research, and grants of the Mochida Memorial Foundation for Medical and Pharmaceutical Research, the Nakatomi Foundation for Health Medical Research, and the Cell Science Research Foundation.

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