Nuclear factor kappa B activity is essential for matrix metalloproteinase-1 and-3 upregulation in rabbit dermal fibroblasts

Expression of matrix metalloproteinases (MMPs)-1 and -3 in fibroblasts is u pregulated by pro-inflammatory cytokines and growth factors during prolifer ative inflammatory processes, including wound healing and rheumatoid arthri tis. The Activator Protein-1 (AP-1) transcription factor is essential but, we show here, not sufficient for upregulation because platelet derived grow th factor (PDGF) and basic fibroblast growth factor (bFGF), which strongly activate AP-1, poorly induce MMP-1 and -3. Interleukin-1 alpha, which activ ates nuclear factor-kappa B (NF-kappa B), synergistically upregulates MMP-1 and -3 expression in the presence of bFGF or PDGF. Adenovirus mediated ove rexpression of I kappa B alpha, the inhibitor of NF-kappa B, completely sup presses MMP-1 and -3 protein and mRNA expression. Hence, we show for the fi rst time that (NF-kappa B) activity is also essential for MMP-1 and -3 upre gulation. (C) 1999 Academic Press.