Ox-LDL suppresses PMA-induced MMP-9 expression and activity through CD36-mediated activation of PPAR-gamma.
- Author:
Kyoung Jin LEE
1
;
Hyun A KIM
;
Pyeung Hyeun KIM
;
Han soo LEE
;
Kyung Ran MA
;
Jeong Hyun PARK
;
Dae Joong KIM
;
Jang Hee HAHN
Author Information
1. Vascular System Research Center, College of Natural Sciences Kangwon National University, Chunchon 200-701, Korea. jhahn@kangwon.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
CD36;
MMP-9;
monocyte;
ox-LDL;
PMA;
PPAR-gamma
- MeSH:
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
- From:Experimental & Molecular Medicine
2004;36(6):534-544
- CountryRepublic of Korea
- Language:English
-
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.
