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

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.