Thrombin-induced expression of RANTES mRNA through protease activated receptor-1 in human synovial fibroblasts.
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.
Hirano
F
F
Second Department of Internal Medicine, Asahikawa Medical College, Japan. fhirano@asahikawa-med.ac.jp
Kobayashi
A
A
Hirano
Y
Y
Nomura
Y
Y
Fukawa
E
E
Makino
I
I
D051017:Apoptosis Regulatory Proteins; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000235:genetics*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006367:HeLa Cells; D015801:Helminth Proteins / Q000032:analysis / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology*; D014162:Transfection; D001616:beta-Galactosidase / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D018946:Chemokine CCL5; D015801:Helminth Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C101296:prostate apoptosis response-4 protein; C097238:PAR-3 protein, C elegans; D017346:Protein Serine-Threonine Kinases; D001616:beta-Galactosidase; D013917:Thrombin