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OBJECTIVE: To determine whether, in human fibroblasts and chondrosarcoma cells, the regulation of interleukins (IL)-6, 8, and 11 and matrix metalloproteinases (MMP)-1, 3, and 13, and their tissue inhibitor TIMP-1, depends on the transcription factor nuclear factor-kappaB (NF-kappaB). METHODS: Fibroblasts and chondrosarcoma cells were effectively infected with an adenovirus encoding human IkappaBalpha, and inhibition of NF-kappaB function was observed. The induction of MMP and IL-6, 8, and 11 by various stimuli was assessed by ELISA. RESULTS: The induction of IL-6 and IL-8 clearly depended on NF-kappaB in both fibroblasts and chondrosarcoma cells, irrespective of stimulus, but IkappaBalpha overexpression had little effect on IL-11. MMP-1, -3, and -13 were also inhibited, but TIMP-1 was unaffected. CONCLUSION: NF-kappaB appears to play an important and selective role in MMP induction in human fibroblasts and chondrosarcoma cells. This suggests there are NF-kappaB dependent mechanisms of cartilage destruction in rheumatoid arthritis, and supports the concept that there are similarities in the regulation of inflammatory and destructive pathways in that disease.


Journal article


J Rheumatol

Publication Date





2078 - 2089


Arthritis, Rheumatoid, Chondrosarcoma, Cytokines, DNA-Binding Proteins, Fibroblasts, Gene Transfer Techniques, Genetic Vectors, Humans, I-kappa B Proteins, Inflammation, Interleukin-1, Matrix Metalloproteinases, NF-KappaB Inhibitor alpha, NF-kappa B, Phorbol Esters, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha