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

被引:50
作者
Elliott, SF [1 ]
Coon, CI [1 ]
Hays, E [1 ]
Stadheim, TA [1 ]
Vincenti, MP [1 ]
机构
[1] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Med, Hanover, NH 03755 USA
来源
ARTHRITIS AND RHEUMATISM | 2002年 / 46卷 / 12期
关键词
D O I
10.1002/art.10675
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 NIMP-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 RTPCR 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 NIMP-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.
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页码:3230 / 3239
页数:10
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