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- Title
The rapid lipopolysaccharide-induced release of matrix metalloproteinases 9 is suppressed by simvastatin.
- Authors
Li, Dan‐Dong; Pang, Hong‐Gang; Song, Jin‐Ning; Huang, Huan; Zhang, Ming; Zhao, Yong‐Lin; Sun, Peng; Zhang, Bin‐Fei; Ma, Xu‐Dong
- Abstract
A rapid increase in matrix metalloproteinase-9 (MMP-9) expression by stimulated leukocytes is common in many diseases. Recent evidence suggests that the beneficial effects of statins are mediated in part by the suppression of MMP-9 release. In this study, we investigated the effect of statin on MMP-9 expression and its antagonist, tissue inhibitor of metalloproteinase-1 (TIMP-1) in LPS-stimulated leukocytes. Rat neutrophils and monocytes were stimulated with lipopolysaccharide (LPS) in the presence of simvastatin. MMP-9 secretion and mRNA expression were analyzed using ELISA and RT-PCR, respectively. Total MMP-9 protein production was measured by Western blot analysis. Potential signal transduction pathways responsible for MMP-9 production were investigated using luciferase reporter assays (NF-κB), pull-down assays (RhoA), and pharmacological inhibition. Our data show that MMP-9 and TIMP-1 expression are differentially induced by LPS in neutrophils and monocytes. We showed that rapid MMP-9 release occurred mainly via secretion from intracellular stores. Moreover, we showed that statin significantly suppressed LPS-induced MMP-9 release and mRNA expression in a time- and concentration-dependent manner. We also evaluated that simvastain postponed the rapid LPS-induced MMP-9 release for about 20 min. In conclusion, we demonstrated that the suppressive effect of simvastatin on LPS-stimulated MMP-9 release does not occur via the NF-κB pathway and the MAPKs pathway, but via the RhoA/ROCK pathway.
- Subjects
METALLOPROTEINASES; LIPOPOLYSACCHARIDES; ENDOTOXINS; SIMVASTATIN; TETRAHYDROPYRANYL compounds
- Publication
Cell Biology International, 2015, Vol 39, Issue 7, p788
- ISSN
1065-6995
- Publication type
Article
- DOI
10.1002/cbin.10445