Bondeson, Jan, Brennan, F., Foxwell, B. and Feldmann, M. 2000. Effective adenoviral transfer of IkappaBalpha into human fibroblasts and chondrosarcoma cells reveals that the induction of matrix metalloproteinases and proinflammatory cytokines is nuclear factor-kappaB dependent. The Journal of Rheumatology 27 (9) , pp. 2078-2089. |
Abstract
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.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Medicine |
Subjects: | R Medicine > R Medicine (General) |
Uncontrolled Keywords: | Arthritis, Rheumatoid/enzymology, Arthritis, Rheumatoid/immunology*, Arthritis, Rheumatoid/physiopathology, Chondrosarcoma/enzymology, Cytokines/biosynthesis, Cytokines/drug effects, Cytokines/genetics*, DNA-Binding Proteins/genetics*, Fibroblasts/drug effects, Fibroblasts/enzymology, Gene Transfer Techniques, Genetic Vectors/diagnostic use, Humans, I-kappa B Proteins, Inflammation/enzymology, Inflammation/genetics*, Interleukin-1/pharmacology, Matrix Metalloproteinases/biosynthesis, Matrix Metalloproteinases/drug effects, Matrix Metalloproteinases/genetics*, NF-kappa B/genetics*, Phorbol Esters/pharmacology, Tumor Cells, Cultured/drug effects, Tumor Cells, Cultured/enzymology, Tumor Necrosis Factor-alpha/pharmacology |
ISSN: | 0315-162X |
Last Modified: | 30 Jun 2017 03:26 |
URI: | https://orca.cardiff.ac.uk/id/eprint/57288 |
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