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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).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.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.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.

Type

Journal article

Journal

The Journal of rheumatology

Publication Date

09/2000

Volume

27

Pages

2078 - 2089

Addresses

Kennedy Institute of Rheumatology, London, UK.

Keywords

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