Increased expression of pro-inflammatory cytokines and metalloproteinase-1 by TGF-β1 in synovial fibroblasts from rheumatoid arthritis and normal individuals

Abstract

SUMMARY Transforming growth factor (TGF)-β1 is expressed abundantly in the rheumatoid synovium. In this study, the inflammatory effect of TGF-β1 in rheumatoid arthritis (RA) was investigated using cultured fibroblast-like synoviocytes (FLS) from RA and osteoarthritis (OA) patients, as well as non-arthritic individuals. mRNA expressions of IL-1β, tumour necrosis factor (TNF)-α, IL-8, macrophage inflammatory protein (MIP)-1α and metalloproteinase (MMP)-1 were increased in RA and OA FLS by TGF-β1 treatment, but not in non-arthritic FLS. Enhanced protein expression of IL-1β, IL-8 and MMP-1 was also observed in RA FLS. Moreover, TGF-β1 showed a synergistic effect in increasing protein expression of IL-1β and matrix metalloproteinase (MMP)-1 with TNFα and IL-1β, respectively. Biological activity of IL-1 determined by mouse thymocyte proliferation assay was also enhanced by 50% in response to TGF-β1 in the culture supernatant of RA FLS. DNA binding activities of nuclear factor (NF)-κB and activator protein (AP)-1 were shown to increase by TGF-β1 as well. These results suggest that TGF-β1 contributes for the progression of inflammation and joint destruction in RA, and this effect is specific for the arthritic synovial fibroblasts.