Bcl-3 is an interleukin-1-responsive gene in chondrocytes and synovial fibroblasts that activates transcription of the matrix metalloproteinase 1 gene

Arthritis Rheum. 2002 Dec;46(12):3230-9. doi: 10.1002/art.10675.


Objective: To define the role of Bcl-3, a member of the inhibitor of nuclear factor kappaB (NF-kappaB) family and a known regulator of NF-kappaB, in interleukin-1 (IL-1)-induced matrix metalloproteinase 1 (MMP-1) transcription in chondrocytes and synovial fibroblasts.

Methods: SW-1353 cells, a human chondrosarcoma cell line, were stimulated with IL-1beta, and the harvested RNA was subjected to microarray analysis and quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). The SW-1353 cells were stimulated with IL-1 or transfected with a plasmid that constitutively expressed Bcl-3, and then MMP-1 messenger RNA (mRNA) expression was assayed by quantitative real-time RT-PCR. SW-1353 cells were transfected with antisense oligonucleotides to Bcl-3, and IL-1-induced MMP-1 mRNA expression was assayed by quantitative RT-PCR. SW-1353 cells and rabbit synovial fibroblasts were transfected with a 4.3-kb human MMP-1 promoter construct along with Bcl-3 and NF-kappaB1 expression constructs, and MMP-1 transcription was assayed.

Results: Microarray analysis and real-time RT-PCR showed Bcl-3 to be an IL-1beta-responsive gene in SW-1353 cells. Exogenous expression of Bcl-3 in SW-1353 cells activated MMP-1 transcription. Endogenous Bcl-3 expression was required for IL-1beta induction of MMP-1 gene expression. Bcl-3 also activated MMP-1 transcription in primary synovial fibroblasts. We showed previously that NF-kappaB1 contributes to IL-1beta induction of MMP-1 transcription in stromal cells. We showed here that Bcl-3 can cooperate with NF-kappaB1 to activate MMP-1 transcription in SW-1353 cells.

Conclusion: These data define a new role for Bcl-3 in joint cells as an IL-1beta-responsive early gene involved in cell-mediated cartilage remodeling. Our findings implicate Bcl-3 as an important contributor to chronic inflammatory disease states, such as osteoarthritis and rheumatoid arthritis.

Publication types

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

MeSH terms

  • Animals
  • B-Cell Lymphoma 3 Protein
  • Cell Line
  • Chondrocytes / physiology*
  • Computer Systems
  • Fibroblasts / physiology*
  • Gene Expression Regulation / drug effects
  • Humans
  • Interleukin-1 / pharmacology*
  • Matrix Metalloproteinase 1 / genetics*
  • NF-kappa B / physiology
  • Oligonucleotide Array Sequence Analysis
  • Promoter Regions, Genetic / physiology
  • Protein Isoforms / physiology
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / physiology
  • Rabbits
  • Reverse Transcriptase Polymerase Chain Reaction
  • Synovial Membrane / physiology*
  • Transcription Factors
  • Transcription, Genetic / physiology*


  • B-Cell Lymphoma 3 Protein
  • BCL3 protein, human
  • Interleukin-1
  • NF-kappa B
  • Protein Isoforms
  • Proto-Oncogene Proteins
  • Transcription Factors
  • Matrix Metalloproteinase 1