Yulan Zhao1, Shuli Zhou, Chew-Kiat Heng. 1. Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Abstract
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. METHODS AND 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). Copyright 2008 S. Karger AG, Basel.
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. METHODS AND 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). Copyright 2008 S. Karger AG, Basel.
Authors: Sara Abouelasrar Salama; Mirre De Bondt; Mieke De Buck; Nele Berghmans; Paul Proost; Vivian Louise Soares Oliveira; Flavio A Amaral; Mieke Gouwy; Jo Van Damme; Sofie Struyf Journal: Front Immunol Date: 2020-05-14 Impact factor: 7.561