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

M Bond1, A H Baker, A C Newby

  • 1Bristol Heart Institute, University of Bristol, Bristol, BS2 8HW, United Kingdom.

Biochemical and Biophysical Research Communications
|October 26, 1999
PubMed

Insights

Nuclear factor-kappaB (NF-kappaB) activity is crucial for the expression of matrix metalloproteinases (MMPs)-1 and -3, working alongside Activator Protein-1 (AP-1) during inflammatory processes like wound healing.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Matrix metalloproteinases (MMPs)-1 and -3 are upregulated in inflammatory conditions like wound healing and rheumatoid arthritis.
  • Pro-inflammatory cytokines and growth factors stimulate MMP expression, involving transcription factors Activator Protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB).

Purpose of the Study:

  • To investigate the essential role of NF-kappaB in the upregulation of MMP-1 and -3 expression.
  • To determine if AP-1 activation alone is sufficient for MMP induction.

Main Methods:

  • Fibroblast cultures were treated with growth factors (PDGF, bFGF) and Interleukin-1alpha.
  • Adenovirus-mediated overexpression of IkappaBalpha (NF-kappaB inhibitor) was used to block NF-kappaB activity.
  • MMP-1 and -3 protein and mRNA levels were quantified.

Main Results:

  • Platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) strongly activated AP-1 but poorly induced MMP-1 and -3.
  • Interleukin-1alpha, activating NF-kappaB, synergistically upregulated MMP-1 and -3 expression with bFGF or PDGF.
  • Inhibition of NF-kappaB by IkappaBalpha overexpression completely suppressed MMP-1 and -3 expression.

Conclusions:

  • AP-1 activation is necessary but not sufficient for MMP-1 and -3 upregulation.
  • NF-kappaB activity is essential for the synergistic upregulation of MMP-1 and -3 expression in response to inflammatory stimuli.

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