title: 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.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Kennedy Institute of Rheumatology, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Bondeson
authors.forename: F
authors.initials: F
authors.lastname: Brennan
authors.forename: B
authors.initials: B
authors.lastname: Foxwell
authors.forename: M
authors.initials: M
authors.lastname: Feldmann
mesh_terms: D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000276:immunology* / Q000503:physiopathology; D002813:Chondrosarcoma / Q000201:enzymology; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D020672:I-kappa B Proteins; D007249:Inflammation / Q000201:enzymology / Q000235:genetics*; D007375:Interleukin-1 / Q000494:pharmacology; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics*; D010703:Phorbol Esters / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D007375:Interleukin-1; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D010703:Phorbol Esters; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D020782:Matrix Metalloproteinases