Aspirin Inhibits MMP-2 and MMP-9 Expression and Activity Through PPARα/γ and TIMP-1-Mediated Mechanisms in Cultured Mouse Celiac Macrophages

摘要

Aspirin is an anti-inflammatory drug, and has been widely used for the prevention of cardio-cerebrovascular events. Matrix metalloproteinase (MMP)-2 and MMP-9 can degrade the extracellular matrix and may be critical for the development and disruption of atherosclerotic plaques, while tissue inhibitor of metalloproteinase (TIMP)-1 may inhibit the degradation of extracellular matrix. The purpose of present study was to investigate the inhibitory effects of aspirin on MMP-2 and MMP-9 expression and activity in cultured mouse celiac macrophages, and to determine the possible mechanisms. The results showed that MMP-2/9 mRNA expression and release were significantly decreased after cultured mouse celiac macrophages were treated with aspirin 12.5–50 μg/ml for 24 h, while the TIMP-1 mRNA expression and release, and peroxisome proliferator-activated receptor (PPAR) α/γ mRNA expression were increased after the same treatment. Moreover the aspirin-induced down-regulation of MMP-2/9 mRNA expression and reduction of MMP-9 release were notably alleviated after pretreatment with specific inhibitors of PPARα/γ. These results suggested that aspirin could inhibit the expression and release of MMP-2/9 by up-regulation of PPARα/γ gene expression, and also inhibit the activity of MMP-2/9 by induction of TIMP-1 expression, which might be good for the stabilization of atherosclerotic plaques and the prevention of cardio-cerebrovascular events.