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

J Rheumatol. 2000 Sep;27(9):2078-89.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Humans
  • I-kappa B Proteins*
  • Inflammation / enzymology
  • Inflammation / genetics*
  • Interleukin-1 / pharmacology
  • Matrix Metalloproteinases / biosynthesis
  • Matrix Metalloproteinases / drug effects
  • Matrix Metalloproteinases / genetics*
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / genetics*
  • Phorbol Esters / pharmacology
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / enzymology
  • Tumor Necrosis Factor-alpha / pharmacology


  • Cytokines
  • DNA-Binding Proteins
  • I-kappa B Proteins
  • Interleukin-1
  • NF-kappa B
  • NFKBIA protein, human
  • Phorbol Esters
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha
  • Matrix Metalloproteinases