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Statins inhibit matrix metalloproteinase release from human lung fibroblasts

K Kamio1, X D Liu, H Sugiura

  • 1University of Nebraska Medical Center, Omaha, NE 68198-5910, USA.

The European Respiratory Journal
|October 3, 2009
PubMed

Insights

Statins, including atorvastatin, inhibit the release and expression of matrix metalloproteinases (MMPs) from human lung fibroblasts. This action may modulate fibroblast-mediated tissue remodeling processes.

Area of Science:

  • Pharmacology
  • Cell Biology
  • Biochemistry

Background:

  • Statins exhibit pleiotropic effects, including the inhibition of matrix metalloproteinase (MMP) release from various cell types.
  • Human lung fibroblasts are crucial in tissue remodeling processes and release MMPs.

Purpose of the Study:

  • To investigate the potential of statins to inhibit MMP release from human lung fibroblasts.
  • To explore the impact of statins on fibroblast-mediated collagen degradation.

Main Methods:

  • Utilized monolayer and 3D collagen gel cultures of human lung fibroblasts.
  • Induced MMP release and mRNA expression using cytokines (TNF-α, IL-1α).
  • Assessed collagen degradation via hydroxyproline quantification and evaluated statin effects (atorvastatin, simvastatin, fluvastatin).

Main Results:

  • Statins significantly inhibited MMP-1 and MMP-3 release and mRNA expression in both culture systems.
  • Atorvastatin also inhibited MMP-9 release in 3D cultures.
  • Atorvastatin mitigated cytokine and neutrophil elastase-induced collagen degradation, an effect reversible by mevalonate and geranylgeranyl-pyrophosphate.

Conclusions:

  • Statins effectively inhibit MMP release and expression in human lung fibroblasts.
  • These findings suggest statins can modulate fibroblast-mediated tissue remodeling by inhibiting MMPs.

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