Nuclear factor κB/p50 activates an element in the distal matrix metalloproteinase 1 promoter in interleukin-1β-stimulated synovial fibroblasts
✍ Scribed by Matthew P. Vincenti; Charles I. Coon; Constance E. Brinckerhoff
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 794 KB
- Volume
- 41
- Category
- Article
- ISSN
- 0004-3591
No coin nor oath required. For personal study only.
✦ Synopsis
Objective. To determine how interleukin-1 (IL-1), through activation of collagenase 1 (matrix metalloproteinase 1 [MMP-I]) 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 KB (NF-KB).
Conclusion. These studies demonstrate, for the first time, a role for NF-KB in the induction of MMP-1, and suggest a mechanism of NF-KB-mediated cartilage degradation in rheumatoid arthritis.
Rheumatoid arthritis (RA) is a severe, debilitating disease that is characterized by chronic inflammation