Simvastatin as a Modulator of Tissue Remodeling through Inhibition of Matrix Metalloproteinase (MMP) Release from Human Lung Fibroblasts

Background: Statins can regulate the production of pro-inflammatory cytokines and inhibit MMP production or activation in a variety of types of cells.This study evaluated whether statins would inhibit MMP release from human lung fibroblasts, which play a major role in remodeling processes.Methods: This study, using an in-vitro model (three-dimensional collagen gel contraction system), evaluated the effect of cytokines (tumor necrosis factor-α, TNF-a and interleukin-1β, IL-1b) on the MMP release and MMP activation from human lung fibroblasts.Collagen degradation induced by cytokines and neutrophil elastase (NE) was evaluated by quantifying hydroxyproline.Results: In three-dimensional collagen gel cultures (3D cultures) where cytokines (TNF-a and IL-1b) can induce the production of MMPs by fibroblasts, it was found that simvastatin inhibited MMP release.In 3D cultures, cytokines together with NE induced collagen degradation and can lead to activation of the MMP, which was inhibited by simvastatin.Conclusion: Simvastatin may play a role in regulating human lung fibroblast functions in repair and remodeling processes by inhibiting MMP release and the conversion from the latent to the active form of MMP.