Exp Mol Med.
2004 Dec;36(6):534-544.
Ox-LDL suppresses PMA-induced MMP-9 expression and activity through CD36-mediated activation of PPAR-gamma
- Affiliations
-
- 1Vascular System Research Center, College of Natural Sciences Kangwon National University, Chunchon 200-701, Korea. jhahn@kangwon.ac.kr
- 2Department of Anatomy and Cell Biology, College of Natural Sciences Kangwon National University, Chunchon 200-701, Korea.
- 3Department of Clinical Pathology, College of Medicine, College of Natural Sciences Kangwon National University, Chunchon 200-701, Korea.
- 4Division of Life Sciences, College of Natural Sciences Kangwon National University, Chunchon 200-701, Korea.
Abstract
- During chronic inflammatory response, mono- cytes/macrophages produce 92-kDa matrix metalloproteinase-9 (MMP-9), which may contribute to their extravasation, migration and tissue remodeling. Activation of peroxisome proliferator- activated factor receptor-gamma (PPAR-gamma) has been shown to inhibit MMP-9 activity. To evaluate whether ox-LDL, a PPAR-gamma activator, inhibits PMA-induced MMP-9 expression and activity, and if so, whether CD36 and PPAR-gamma are involved in this process, we investigated the effect of ox-LDL on MMP-9 expression and activity in PMA-activated human monocytic cell line U937. PMA-induced MMP-9 expression and activity were suppressed by the treatment with ox-LDL (50 micrigram/ml) or PPAR-gamma activators such as troglitazone (5 micrometer), ciglitazone (5 micrometer), and 15d- PGJ2 (1 micrometer) for 24 h. This ox-LDL or PPAR-gamma activator-mediated inhibition of micrometer P-9 activity was diminished by the pre-treatment of cells with a blocking antibody to CD36, or PGF2a (0.3 micrometer), which is a PPAR-gamma inhibitor, as well as overexpression of a dominant-negative form of CD36. Taken together, these results suggest that ox-LDL suppresses PMA-induced MMP-9 expression and activity through CD36-mediated activation of PPAR-gamma.
MeSH Terms
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Antibodies, Blocking/pharmacology
Antigens, CD36/immunology/*physiology
Cells, Cultured
Chromans/pharmacology
Gelatinase B/antagonists & inhibitors/genetics/*metabolism
Humans
Lipoproteins, LDL/pharmacology/*physiology
Monocytes/drug effects/*enzymology/metabolism
NF-kappa B/antagonists & inhibitors
PPAR gamma/*metabolism
Prostaglandin D2/*analogs & derivatives/pharmacology
RNA, Messenger/analysis/metabolism
Research Support, Non-U.S. Gov't
Tetradecanoylphorbol Acetate/antagonists & inhibitors/pharmacology
Thiazolidinediones/pharmacology
Transcription, Genetic/drug effects
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