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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

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.

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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
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: http://orca.cf.ac.uk/id/eprint/57288

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