Aspirin inhibits MMP-2 and MMP-9 expression and activity through PPARalpha/gamma and TIMP-1-mediated mechanisms in cultured mouse celiac macrophages.
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 microg/ml for 24 h, while the TIMP-1 mRNA expression and release, and peroxisome proliferator-activated receptor (PPAR) alpha/gamma 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 PPARalpha/gamma. These results suggested that aspirin could inhibit the expression and release of MMP-2/9 by up-regulation of PPARalpha/gamma 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.
Yiqin
Yao
Y
Department of Pharmacology, Medical College of Soochow University, Suzhou 215123, People's Republic of China.
Meilin
Xie
X
Jie
Xue
X
Keping
Zhang
Z
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D047493:PPAR alpha / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D047493:PPAR alpha; D047495:PPAR gamma; D010975:Platelet Aggregation Inhibitors; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D001241:Aspirin