title: Thrombin receptor mediated signals induce expressions of interleukin 6 and granulocyte colony stimulating factor via NF-kappa B activation in synovial fibroblasts.
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 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.
authors.affiliation: Drug Discovery Research Laboratories, Kaken Pharmaceutical Co, Ltd, Kyoto, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Shin
authors.forename: I
authors.initials: I
authors.lastname: Kitajima
authors.forename: T
authors.initials: T
authors.lastname: Nakajima
authors.forename: Q
authors.initials: Q
authors.lastname: Shao
authors.forename: T
authors.initials: T
authors.lastname: Tokioka
authors.forename: I
authors.initials: I
authors.lastname: Takasaki
authors.forename: N
authors.initials: N
authors.lastname: Hanyu
authors.forename: T
authors.initials: T
authors.lastname: Kubo
authors.forename: I
authors.initials: I
authors.lastname: Maruyama
mesh_terms: 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
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D018179:Receptors, Thrombin; D016179:Granulocyte Colony-Stimulating Factor