Ann Rheum Dis 1999;58:55-60 ( January )

Extended reports

Thrombin receptor mediated signals induce expressions of interleukin 6 and granulocyte colony stimulating factor via NF-B activation in synovial fibroblasts Hiroshi Shin,^{a b} Isao Kitajima,^b Toshihiro Nakajima,^{b c} Qing Shao,^b Takeshi Tokioka,^b Ikuko Takasaki,^b Naohiro Hanyu,^b Toshikazu Kubo,^d Ikuro Maruyama^b

^a Drug Discovery Research Laboratories, Kaken Pharmaceutical Co, Ltd, Kyoto, Japan, ^b Departments of Laboratory and Molecular Medicine Kagoshima University, Kagoshima, Japan, ^c Institute of Applied Biochemistry, Tsukuba University, Ibaraki, Japan, ^d Department of Orthopaedic Surgery, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Japan

Correspondence to: Dr I Kitajima, Department of Laboratory and Molecular Medicine, Kagoshima University School of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890-8250, Japan.

Accepted for publication 23 September 1998

OBJECTIVETo clarify the mechanism of thrombin receptor mediated signal transduction and the induction of cytokines by thrombin stimulation in rheumatoid synovial fibroblasts.
METHODSCytokines 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 -chloramphenicol acetyltransferase (CAT) assay, and immunostaining for NF-B subunit molecule was performed.
RESULTSThrombin stimulation activated the inducible transcription factor NF-B, and then induced subsequent expressions of interleukin 6 (IL6) and granulocyte colony stimulating factor (G-CSF) in the cells.
CONCLUSIONThrombin receptor mediated signal transduction could induce the expressions of IL6 and G-CSF, and increase inflammatory events in the cavum articulare via NF-B activation.

Keywords: thrombin; NF-B; cytokine; synovial cells

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© 1999 by Annals of the Rheumatic Diseases
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