Effects of simvastatin on matrix metalloproteinase regulation in IL-1 beta-induced SW1353 cells

Abstract

The present study shows the basis for the anti-inflammatory effects of statins in interleukin 1 beta (IL-15) induced SW1353 chondrosarcoma cell-line. The cells were pre-treated with simvastatin (5 mu M, 10 mu M, and 50 mu M), followed by IL-1 beta (5 ng/mL) stimulation. Effects of simvastatin on cell viability and cytotoxicity of chondrocytes were measured with WST-1 and lactate dehydrogenase (LDH) assays, respectively. Under inflammatory conditions, in the absence/presence of simvastatin, the changes in matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase-1 (TIMP-1) expression levels were examined. Expression levels of MMP-1, -2, -3, -9, -13, and TIMP-1 and -2 were examined by qPCR. MMP-1, -9, -13, TIMP-1, and -2 levels were also determined by Western blotting. Gelatin zymography was performed to analyze the released and intracellular MMP-2 and MMP-9 activity levels. The results showed that simvastatin downregulated the degradation related genes MMP3, MMP-13, MMP-2, MMP-9 and TIMP-2 in a dose-dependent manner.