The effects of the immunosuppressant rapamycin on the growth of rheumatoid arthritis (RA) synovial fibroblast

Author:

Migita K1,Eguchi K1,Aoyagi T21,Tsukada T1,Tsuboi M1,Kawabe Y1,Nagataki S1

Affiliation:

1. First Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki

2. Department of Orthopaedics, National Ureshino Hospital, Ureshino, Japan

Abstract

SUMMARY RA is a chronic inflammatory disease characterized by mononuclear cell infiltration and the overgrowth of synovial fibroblast. This invasive growth of synovial tissues corresponds with the progressive destruction of articular carilage and bone. Several immunosuppresive agents, such as cyclophosphamide, cyclosporin A and mizoribine, have been clinically used to control disease progresssion, though relatively little is known of their effects on rheumatoid synovium. Rapamycin exhibits a strong immunosuppressive activity by acting on T cell signalling pathways. In the present study we examined the effects of rapamycin on the growth of synovial fibroblast isolated from RA patients. Platelet-derived growth factor (PDGF) is a potent growth factor in synovial fibroblasts isolated from RA patients. PDGF and serum stimulation resulted in a rapid phosphorylation of tyrosine and activation of mitogen-activated protein kinase (MAP kinase), 70-kD-S6 kinase (P70S6K) and 90-kD-S6 kinase (P90rsk). Rapamycin, a macrolide immunosuppressant, inhibited completely growth factor-induced synovial fibroblast proliferation and P70S6K activation. In contrast, tyrosine phosphorylation and activation of MAP kinases and P90rsk were not influenced by rapamycin treatment. Our data demonstrate that growth factor-mediated P70S6K activation is closely related to the growth of synovial fibroblast, and suggest the efficacy of rapamycin for controlling synovial hyperplasia in RA.

Publisher

Oxford University Press (OUP)

Subject

Immunology,Immunology and Allergy

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