Thrombin receptor mediated signals induce expressions of interleukin 6 and granulocyte colony stimulating factor via NF-kappa B activation in synovial fibroblasts.
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 kappa-chloramphenicol acetyltransferase (CAT) assay, and immunostaining for NF-kappa B subunit molecule was performed.


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


CONCLUSIONS
Thrombin receptor mediated signal transduction could induce the expressions of IL6 and G-CSF, and increase inflammatory events in the cavum articulare via NF-kappa B activation.
Shin
H
H
Drug Discovery Research Laboratories, Kaken Pharmaceutical Co, Ltd, Kyoto, Japan.
Kitajima
I
I
Nakajima
T
T
Shao
Q
Q
Tokioka
T
T
Takasaki
I
I
Hanyu
N
N
Kubo
T
T
Maruyama
I
I
D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism*; D018929:Cell Culture Techniques; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D018179:Receptors, Thrombin / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013583:Synovial Membrane / Q000378:metabolism*; D014178:Translocation, Genetic
D016207:Cytokines; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D018179:Receptors, Thrombin; D016179:Granulocyte Colony-Stimulating Factor