Celecoxib inhibits serum amyloid a-induced matrix metalloproteinase-10 expression in human endothelial cells.
BACKGROUND
Although serum amyloid A (SAA) is an established biomarker of coronary artery disease (CAD), its direct role in matrix degradation is obscure. This study investigated the effect of SAA on the expression of matrix metalloproteinase-10 (MMP-10) in endothelial cells. The effect of celecoxib on SAA-dependent MMP-10 expression and its possible mediator were also investigated.


RESULTS
From our time course microarray screening, SAA (20 microg/ml) was found to increase MMP-10 mRNA expression over time (4-48 h) in human endothelial cells. Quantitative real-time PCR confirmed this transcriptional induction. Correspondingly, secreted MMP-10 protein was also markedly induced by SAA treatment for 24 h in a dose-dependent manner. We further examined cyclooxygenase-2 (COX-2) and its major product, prostaglandin E(2) (PGE(2)), as possible mediators of MMP-10 induction. Direct PGE(2) treatment could result in MMP-10 induction. Celecoxib, a selective COX-2 inhibitor, suppressed MMP-10 secretion induced by SAA.


CONCLUSIONS
SAA induced MMP-10 expression and celecoxib prevented its induction. MMP-10 induction was at least partly mediated by PGE(2).
Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Yulan
Y
Zhao
Shuli
S
Zhou
Chew-Kiat
CK
Heng
D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D015232:Dinoprostone / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D053506:Matrix Metalloproteinase 10; D061965:Matrix Metalloproteinase Inhibitors; D011720:Pyrazoles / Q000494:pharmacology*; D000685:Serum Amyloid A Protein / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology*
D061965:Matrix Metalloproteinase Inhibitors; D011720:Pyrazoles; D000685:Serum Amyloid A Protein; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C511770:MMP10 protein, human; D053506:Matrix Metalloproteinase 10; D000068579:Celecoxib; D015232:Dinoprostone