Nuclear factor κB/p50 activates an element in the distal matrix metalloproteinase 1 promoter in interleukin‐1β‐stimulated synovial fibroblasts

MP Vincenti, CI Coon… - Arthritis & Rheumatism …, 1998 - Wiley Online Library
MP Vincenti, CI Coon, CE Brinckerhoff
Arthritis & Rheumatism: Official Journal of the American College …, 1998Wiley Online Library
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 …
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 κB (NF‐κB).
Conclusion
These studies demonstrate, for the first time, a role for NF‐κB in the induction of MMP‐1, and suggest a mechanism of NF‐κB‐mediated cartilage degradation in rheumatoid arthritis.
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