Effective adenoviral transfer of I kappa B alpha into human fibroblasts and chondrosarcoma cells reveals that the induction of matrix metalloproteinases and proinflammatory cytokines is nuclear factor-kappa B dependent

Objective. To determine whether, in human fibroblasts and chondrosarcoma ce lls, the regulation of interleukins (TL)-6, 8, and 11 and matrix metallopro teinases (MMP)-1, 3, and 13, and their tissue inhibitor TIMP-1, depends on the transcription factor nuclear factor-kappa B (NF-kappa B). Methods. Fibroblasts and chondrosarcoma cells were effectively infected wit h an adenovirus encoding human I kappa B alpha, and inhibition of NF-kappa B function was observed. The induction of MMP and IL-6, 8, and 11 by variou s stimuli was assessed by ELISA. Results. The induction of IL-6 and IL-8 clearly depended on NF-kappa B in b oth fibroblasts and chondrosarcoma cells, Irrespective of stimulus, but I k appa B alpha overexpression had little effect on IL-11. MMP-1, -3, and -13 were also inhibited, but TIMP-1 was unaffected. Conclusion. NF-kappa B appears to play an important and selective role in M MP induction in human fibroblasts and chondrosarcoma cells. This suggests t here are NF-kappa B dependent mechanisms of cartilage destruction in rheuma toid arthritis, and supports the concept that there are similarities in the regulation of inflammatory and destructive pathways in that disease.