Abstract
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
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Research Support, Non-U.S. Gov't
MeSH terms
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Arthritis, Rheumatoid / enzymology
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Arthritis, Rheumatoid / immunology*
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Cells, Cultured
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Chemokine CCL3
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Chemokine CCL4
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Cytokines / biosynthesis*
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Cytokines / genetics
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Fibroblasts / drug effects
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Fibroblasts / enzymology
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Fibroblasts / immunology*
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Humans
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Interleukin-1 / biosynthesis
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Interleukin-1 / genetics
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Interleukin-8 / biosynthesis
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Interleukin-8 / genetics
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Macrophage Inflammatory Proteins / biosynthesis
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Macrophage Inflammatory Proteins / genetics
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Matrix Metalloproteinase 1 / biosynthesis*
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Matrix Metalloproteinase 1 / genetics
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NF-kappa B / metabolism
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Osteoarthritis / immunology
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RNA, Messenger / biosynthesis
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Synovial Membrane / cytology
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Synovial Membrane / enzymology
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Synovial Membrane / immunology*
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Transcription Factor AP-1 / metabolism
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Transcriptional Activation
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Transforming Growth Factor beta / pharmacology*
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Transforming Growth Factor beta1
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Tumor Necrosis Factor-alpha / biosynthesis
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Tumor Necrosis Factor-alpha / genetics
Substances
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Chemokine CCL3
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Chemokine CCL4
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Cytokines
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Interleukin-1
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Interleukin-8
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Macrophage Inflammatory Proteins
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NF-kappa B
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RNA, Messenger
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TGFB1 protein, human
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Tgfb1 protein, mouse
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Transcription Factor AP-1
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Transforming Growth Factor beta
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Transforming Growth Factor beta1
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Tumor Necrosis Factor-alpha
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Matrix Metalloproteinase 1