1.Ox-LDL suppresses PMA-induced MMP-9 expression and activity through CD36-mediated activation of PPAR-gamma.
Kyoung Jin LEE ; Hyun A KIM ; Pyeung Hyeun KIM ; Han soo LEE ; Kyung Ran MA ; Jeong Hyun PARK ; Dae Joong KIM ; Jang Hee HAHN
Experimental & Molecular Medicine 2004;36(6):534-544
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.
Antibodies, Blocking/pharmacology
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Antigens, CD36/immunology/*physiology
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Cells, Cultured
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Chromans/pharmacology
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Gelatinase B/antagonists & inhibitors/genetics/*metabolism
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Humans
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Lipoproteins, LDL/pharmacology/*physiology
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Monocytes/drug effects/*enzymology/metabolism
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NF-kappa B/antagonists & inhibitors
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PPAR gamma/*metabolism
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Prostaglandin D2/*analogs & derivatives/pharmacology
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RNA, Messenger/analysis/metabolism
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Research Support, Non-U.S. Gov't
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Tetradecanoylphorbol Acetate/antagonists & inhibitors/pharmacology
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Thiazolidinediones/pharmacology
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Transcription, Genetic/drug effects