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Relaxin induces matrix metalloproteinase-9 through activation of nuclear factor kappa B in human THP-1 cells

Teh-Yuan Ho1, Carol A Bagnell

  • 1Department of Animal Sciences, Rutgers University, New Brunswick, NJ 08901, USA.

Annals of the New York Academy of Sciences
|June 16, 2005
PubMed

Insights

Relaxin enhances matrix metalloproteinase-9 (MMP-9) in THP-1 cells by activating nuclear factor kappa B (NF-kappaB). This mechanism is crucial for understanding tissue remodeling and wound repair processes.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Immunology

Background:

  • Matrix metalloproteinases (MMPs) and relaxin are key regulators of tissue remodeling and wound healing.
  • Macrophages are critical cellular players at wound sites, known to secrete MMPs.
  • Nuclear factor kappa B (NF-kappaB) signaling is implicated in the transcriptional regulation of MMP genes.

Purpose of the Study:

  • To investigate the underlying molecular mechanisms by which relaxin influences MMP expression and activity.
  • To elucidate the role of NF-kappaB signaling in relaxin-mediated MMP regulation in a monocyte/macrophage context.

Main Methods:

  • Utilized the THP-1 monocyte/macrophage cell line for experimental studies.
  • Assessed MMP-9 and MMP-2 protein levels and enzymatic activity in cell-conditioned media.
  • Evaluated NF-kappaB DNA binding activity and the expression of NF-kappaB subunits (p50, p65) and its inhibitor (IkappaB-alpha) using techniques like supershift assays.

Main Results:

  • Relaxin significantly increased both the protein levels and activity of MMP-9 in THP-1 cell supernatants.
  • No significant alterations in MMP-2 activity were observed following relaxin treatment.
  • Relaxin treatment led to enhanced NF-kappaB DNA binding activity, involving activation of p50 and p65 subunits, and a concurrent decrease in IkappaB-alpha levels.

Conclusions:

  • The findings indicate that relaxin promotes MMP-9 expression in THP-1 cells through the activation of the NF-kappaB signaling pathway.
  • This pathway involves the degradation of IkappaB-alpha, leading to the nuclear translocation and activation of NF-kappaB subunits.
  • These results provide critical insights into the molecular basis of relaxin's role in tissue repair and remodeling processes mediated by macrophages.

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