Nuclear factor kappaB 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 upregulated by pro-inflammatory cytokines and growth factors during proliferative inflammatory processes, including wound healing and rheumatoid arthritis. The Activator Protein-1 (AP-1) transcription factor is essential but, we show here, not sufficient for upregulation because platelet derived growth factor (PDGF) and basic fibroblast growth factor (bFGF), which strongly activate AP-1, poorly induce MMP-1 and -3. Interleukin-1alpha, which activates nuclear factor-kappaB (NF-kappaB), synergistically upregulates MMP-1 and -3 expression in the presence of bFGF or PDGF. Adenovirus mediated overexpression of IkappaBalpha, the inhibitor of NF-kappaB, completely suppresses MMP-1 and -3 protein and mRNA expression. Hence, we show for the first time that (NF-kappaB) activity is also essential for MMP-1 and -3 upregulation.
Bond
M
M
Bristol Heart Institute, University of Bristol, Bristol, BS2 8HW, United Kingdom.
Baker
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AH
Newby
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AC
D000256:Adenoviridae; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D004790:Enzyme Induction; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects; D005786:Gene Expression Regulation; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis* / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015854:Up-Regulation
D016207:Cytokines; D016328:NF-kappa B; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D016222:Fibroblast Growth Factor 2; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1