Inhibition of EMMPRIN and MMP-9 Expression by Epigallocatechin-3-Gallate through 67-kDa Laminin Receptor in PMA-Induced Macrophages

Background/Aims: It is well documented that overexpression of EMMPRIN (extracellular matrix metalloproteinase inducer) and MMPs (matrix metalloproteinases) by monocytes/macrophages plays an important role in atherosclerotic plaque rupture. Green tea polyphenol epigallocatechin-3-gallate (EGCG) has a...

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Published in:	Cellular physiology and biochemistry Vol. 39; no. 6; pp. 2308 - 2319
Main Authors:	Wang, Qi-Ming, Wang, Hao, Li, Ya-Fei, Xie, Zhi-Yong, Ma, Yao, Yan, Jian-Jun, Gao, Yi Fan Wei, Wang, Ze-Mu, Wang, Lian-Sheng
Format:	Journal Article
Language:	English
Published:	Basel, Switzerland Cell Physiol Biochem Press GmbH & Co KG 01-01-2016
Subjects:	67-kDa laminin receptor Basigin - metabolism Catechin - analogs & derivatives Catechin - chemistry Catechin - pharmacology Cell Death - drug effects Cell Differentiation - drug effects Cell Line EMMPRIN Epigallocatechin-3-gallate Humans Macrophages - drug effects Macrophages - enzymology Macrophages - metabolism MAP Kinase Signaling System - drug effects Matrix Metalloproteinase 9 - metabolism MMP-9 Original Paper Protein Kinase Inhibitors - pharmacology Receptors, Laminin - metabolism Stabilization of atherosclerotic plaque Tetradecanoylphorbol Acetate - pharmacology Stabilization of atherosclerotic plaque EMMPRIN 67-kDa laminin receptor MMP-9 Epigallocatechin-3-gallate
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Summary:	Background/Aims: It is well documented that overexpression of EMMPRIN (extracellular matrix metalloproteinase inducer) and MMPs (matrix metalloproteinases) by monocytes/macrophages plays an important role in atherosclerotic plaque rupture. Green tea polyphenol epigallocatechin-3-gallate (EGCG) has a variety of pharmacological properties and exerts cardiovascular protective effects. Recently, the 67-kD laminin receptor (67LR) has been identified as a cell surface receptor of EGCG. The aim of the present study was to evaluate the effects of EGCG on the expression of EMMPRIN and MMP-9 in PMA-induced macrophages, and the potential mechanisms underlying its effects. Methods: Human monocytic THP-1 cells were induced to differentiate into macrophages with phorbol 12-myristate 13-acetate (PMA). Protein expression and MMP-9 activity were assayed by Western blot and Gelatin zymography, respectively. Real-time PCR was used to examine EMMPRIN and MMP-9 mRNA expression. Results: We showed that EGCG (10-50µmol/L) significantly inhibited the expression of EMMPRIN and MMP-9 and activation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 and c-Jun N-terminal kinase (JNK) in PMA-induced macrophages. Downregulation of EMMPRIN by gene silencing hindered PMA-induced MMP-9 secretion and expression, indicating an important role of EMMPRIN in the inhibition of MMP-9 by EGCG. Moreover, 67LR was involved in EGCG-mediated suppression of EMMPRIN and MMP-9 expression. Anti-67LR antibody treatment led to abrogation of the inhibitory action of EGCG on the expression of EMMPRIN and MMP-9 and activation of ERK1/2, p38, and JNK. Conclusion: Our results indicate that EGCG restrains EMMPRIN and MMP-9 expression via 67LR in PMA-induced macrophages, which also suggests that EGCG may be a possible therapeutic agent for stabilizing atherosclerotic plaque.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1015-8987 1421-9778
DOI:	10.1159/000447923