Statins inhibit matrix metalloproteinase release from human lung fibroblasts

K. Kamio, Xiang-de Liu, H. Sugiura, S. Togo, S. Kawasaki, X. Wang, Y. Ahn, C. Hogaboam, S. I. Rennard

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Pleiotropic effects of statins have been reported to include inhibition of matrix metalloproteinase (MMP) release from macrophages and endothelial cells. We evaluated whether statins would inhibit MMP release from human lung fibroblasts, which play a major role in remodelling processes. Monolayer and three-dimensional (3D) collagen gel cultures of fibroblasts were used. Cytokines (tumour necrosis factor-α and interleukin-1α) were used to induce MMP release and mRNA expression. Collagen degradation induced by cytokines and neutrophil elastase (NE) was evaluated by quantifying hydroxyproline. Atorvastatin inhibited MMP-1 and -3 release and mRNA expression in both culture systems. Similar results were obtained with simvastatin and fluvastatin. In 3D cultures where cytokines also stimulated MMP-9 release, atorvastatin also inhibited MMP-9 release. In 3D cultures, cytokines together with NE induced collagen degradation, which was also inhibited by atorvastatin. The effect of atorvastatin was reversed by mevalonate and geranylgeranyl-pyrophosphate but not by farnesyl-pyrophosphate. The current data suggest that statins may modulate remodelling processes mediated by fibroblasts by inhibiting MMP release.

Original languageEnglish (US)
Pages (from-to)637-646
Number of pages10
JournalEuropean Respiratory Journal
Volume35
Issue number3
DOIs
StatePublished - Mar 1 2010

Fingerprint

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Matrix Metalloproteinases
Fibroblasts
Cytokines
Lung
Leukocyte Elastase
Collagen
fluvastatin
Matrix Metalloproteinase 9
Matrix Metalloproteinase 3
Messenger RNA
Matrix Metalloproteinase 1
Simvastatin
Hydroxyproline
Interleukin-1
Endothelial Cells
Tumor Necrosis Factor-alpha
Gels
Macrophages
Atorvastatin Calcium

Keywords

  • Collagen
  • Degradation
  • Fibroblasts
  • Matrix metalloproteinases
  • Statins

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Kamio, K., Liu, X., Sugiura, H., Togo, S., Kawasaki, S., Wang, X., ... Rennard, S. I. (2010). Statins inhibit matrix metalloproteinase release from human lung fibroblasts. European Respiratory Journal, 35(3), 637-646. https://doi.org/10.1183/09031936.00134707

Statins inhibit matrix metalloproteinase release from human lung fibroblasts. / Kamio, K.; Liu, Xiang-de; Sugiura, H.; Togo, S.; Kawasaki, S.; Wang, X.; Ahn, Y.; Hogaboam, C.; Rennard, S. I.

In: European Respiratory Journal, Vol. 35, No. 3, 01.03.2010, p. 637-646.

Research output: Contribution to journalArticle

Kamio, K, Liu, X, Sugiura, H, Togo, S, Kawasaki, S, Wang, X, Ahn, Y, Hogaboam, C & Rennard, SI 2010, 'Statins inhibit matrix metalloproteinase release from human lung fibroblasts', European Respiratory Journal, vol. 35, no. 3, pp. 637-646. https://doi.org/10.1183/09031936.00134707
Kamio, K. ; Liu, Xiang-de ; Sugiura, H. ; Togo, S. ; Kawasaki, S. ; Wang, X. ; Ahn, Y. ; Hogaboam, C. ; Rennard, S. I. / Statins inhibit matrix metalloproteinase release from human lung fibroblasts. In: European Respiratory Journal. 2010 ; Vol. 35, No. 3. pp. 637-646.
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