Increased expression of pro-inflammatory cytokines and metalloproteinase-1 by TGF-beta1 in synovial fibroblasts from rheumatoid arthritis and normal individuals

Clin Exp Immunol. 2002 Mar;127(3):547-52. doi: 10.1046/j.1365-2249.2002.01785.x.


Transforming growth factor (TGF)-beta1 is expressed abundantly in the rheumatoid synovium. In this study, the inflammatory effect of TGF-beta1 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-1beta, tumour necrosis factor (TNF)-alpha, IL-8, macrophage inflammatory protein (MIP)-1alpha and metalloproteinase (MMP)-1 were increased in RA and OA FLS by TGF-beta1 treatment, but not in non-arthritic FLS. Enhanced protein expression of IL-1beta, IL-8 and MMP-1 was also observed in RA FLS. Moreover, TGF-beta1 showed a synergistic effect in increasing protein expression of IL-1beta and matrix metalloproteinase (MMP)-1 with TNFalpha and IL-1beta, respectively. Biological activity of IL-1 determined by mouse thymocyte proliferation assay was also enhanced by 50% in response to TGF-beta1 in the culture supernatant of RA FLS. DNA binding activities of nuclear factor (NF)-kappaB and activator protein (AP)-1 were shown to increase by TGF-beta1 as well. These results suggest that TGF-beta1 contributes for the progression of inflammation and joint destruction in RA, and this effect is specific for the arthritic synovial fibroblasts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / enzymology
  • Arthritis, Rheumatoid / immunology*
  • Cells, Cultured
  • Chemokine CCL3
  • Chemokine CCL4
  • Cytokines / biosynthesis*
  • Cytokines / genetics
  • Fibroblasts / drug effects
  • Fibroblasts / enzymology
  • Fibroblasts / immunology*
  • Humans
  • Interleukin-1 / biosynthesis
  • Interleukin-1 / genetics
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / genetics
  • Macrophage Inflammatory Proteins / biosynthesis
  • Macrophage Inflammatory Proteins / genetics
  • Matrix Metalloproteinase 1 / biosynthesis*
  • Matrix Metalloproteinase 1 / genetics
  • NF-kappa B / metabolism
  • Osteoarthritis / immunology
  • RNA, Messenger / biosynthesis
  • Synovial Membrane / cytology
  • Synovial Membrane / enzymology
  • Synovial Membrane / immunology*
  • Transcription Factor AP-1 / metabolism
  • Transcriptional Activation
  • Transforming Growth Factor beta / pharmacology*
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics


  • Chemokine CCL3
  • Chemokine CCL4
  • Cytokines
  • Interleukin-1
  • Interleukin-8
  • Macrophage Inflammatory Proteins
  • NF-kappa B
  • RNA, Messenger
  • TGFB1 protein, human
  • Tgfb1 protein, mouse
  • Transcription Factor AP-1
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha
  • Matrix Metalloproteinase 1