Nuclear factor kappaB/p50 activates an element in the distal matrix metalloproteinase 1 promoter in interleukin-1beta-stimulated synovial fibroblasts

Arthritis Rheum. 1998 Nov;41(11):1987-94. doi: 10.1002/1529-0131(199811)41:11<1987::AID-ART14>3.0.CO;2-8.


Objective: To determine how interleukin-1 (IL-1), through activation of collagenase 1 (matrix metalloproteinase 1 [MMP-1]) transcription in synovial fibroblasts, contributes to cartilage degradation in rheumatoid arthritis.

Methods: Primary rabbit synovial fibroblasts were transiently transfected with MMP-1 promoter/ luciferase constructs, and promoter activity in response to IL-1 was assessed. A minimal IL-1-response element was defined and used to evaluate DNA binding proteins by electrophoretic mobility shift assay and in situ ultraviolet crosslinking assay.

Results: Transcriptional activation of the MMP-1 gene by IL-1 in rabbit synovial fibroblasts required a dorsal-like element, which was located at nucleotide (nt) -3,029, as well as an activator protein 1 site at nt -77. Importantly, an IL-1-induced DNA binding activity that was specific for the dorsal-like element contained the p50 subunit of nuclear factor kappaB (NF-kappaB).

Conclusion: These studies demonstrate, for the first time, a role for NF-kappaB in the induction of MMP-1, and suggest a mechanism of NF-kappaB-mediated cartilage degradation in rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism
  • Base Sequence
  • Binding Sites / genetics
  • Cells, Cultured
  • Collagenases / genetics*
  • Connective Tissue / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / immunology
  • Gene Expression Regulation, Enzymologic / immunology
  • Interleukin-1 / metabolism
  • Interleukin-1 / pharmacology*
  • Matrix Metalloproteinase 1
  • Molecular Sequence Data
  • NF-kappa B / genetics*
  • Promoter Regions, Genetic / physiology*
  • Rabbits
  • Synovial Membrane / cytology*
  • Synovial Membrane / enzymology
  • Transcription Factor AP-1 / immunology
  • Transcription Factor AP-1 / metabolism
  • Transcriptional Activation / immunology


  • DNA-Binding Proteins
  • Interleukin-1
  • NF-kappa B
  • Transcription Factor AP-1
  • Collagenases
  • Matrix Metalloproteinase 1