title: Bcl-3 is an interleukin-1-responsive gene in chondrocytes and synovial fibroblasts that activates transcription of the matrix metalloproteinase 1 gene.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Dartmouth Medical School, Dartmouth College, Hanover, New Hampshire, 03755, USA.
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Elliott
authors.forename: Charles I
authors.initials: CI
authors.lastname: Coon
authors.forename: Ezra
authors.initials: E
authors.lastname: Hays
authors.forename: Terrance A
authors.initials: TA
authors.lastname: Stadheim
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Vincenti
mesh_terms: D000818:Animals; D000081242:B-Cell Lymphoma 3 Protein; D002460:Cell Line; D019902:Chondrocytes / Q000502:physiology*; D003199:Computer Systems; D005347:Fibroblasts / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D016328:NF-kappa B / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000502:physiology; D020033:Protein Isoforms / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000502:physiology*; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; D007375:Interleukin-1; D016328:NF-kappa B; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D020781:Matrix Metalloproteinase 1