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

被引：32

作者：

Migita, K ^{[1
]}

Eguchi, K ^{[1
]}

Aoyagi, T ^{[1
]}

Tsukada, T ^{[1
]}

Tsuboi, M ^{[1
]}

Kawabe, Y ^{[1
]}

Nagataki, S ^{[1
]}

机构：

[1] NATL URESHINO HOSP,DEPT ORTHOPAED,URESHINO,JAPAN

来源：

CLINICAL AND EXPERIMENTAL IMMUNOLOGY | 1996年 / 104卷 / 01期

关键词：

rapamycin; rheumatoid arthritis; synovial fibroblast; protein kinase;

D O I：

10.1046/j.1365-2249.1996.d01-651.x

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 [免疫学];

摘要：

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 patent 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 (P70(S6K)) and 90-kD-S6 kinase (P90(rsk)). Rapamycin, a macrolide immunosuppressant, inhibited completely growth factor-induced synovial fibroblast proliferation and P70(S6K) activation. In contrast, tyrosine phosphorylation and activation of MAP kinases and P90(rsk) were not influenced by rapamycin treatment. Our data demonstrate that growth factor-mediated p70(S6K) activation is closely related to the growth of synovial fibroblast, and suggest the efficacy of rapamycin for controlling synovial hyperplasia in RA.

引用

页码：86 / 91

页数：6

共 29 条

[1]

MOLECULAR-STRUCTURE OF A MAJOR INSULIN MITOGEN-ACTIVATED 70-KDA S6 PROTEIN-KINASE [J].