Ox-LDL suppresses PMA-induced MMP-9 expression and activity through CD36-mediated activation of PPAR-g.
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-g (PPAR-g) has been shown to inhibit MMP-9 activity. To evaluate whether ox-LDL, a PPAR-g activator, inhibits PMA-induced MMP-9 expression and activity, and if so, whether CD36 and PPAR-g 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 mg/ml) or PPAR-g activators such as troglitazone (5 mM), ciglitazone (5 mM), and 15d- PGJ2 (1 mM) for 24 h. This ox-LDL or PPAR-g activator-mediated inhibition of MMP-9 activity was diminished by the pre-treatment of cells with a blocking antibody to CD36, or PGF2a (0.3 mM), which is a PPAR-g 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-g.
Lee
Kyoung Jin
KJ
Vascular System Research Center, Department of Anatomy and Cell Biology, College of Medicine, Kangwon National University, Chunchon 200-701, Korea.
Kim
Hyun A
HA
Kim
Pyeung Hyeun
PH
Lee
Han Soo
HS
Ma
Kyung Ran
KR
Park
Jeong Hyun
JH
Kim
Dae Joong
DJ
Hahn
Jang Hee
JH
D019138:Antibodies, Blocking / Q000494:pharmacology; D018955:CD36 Antigens / Q000276:immunology / Q000502:physiology*; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D047495:PPAR gamma / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D000077288:Troglitazone
C477819:15-deoxyprostaglandin J2; D019138:Antibodies, Blocking; D018955:CD36 Antigens; D002839:Chromans; D008077:Lipoproteins, LDL; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; C099252:oxidized low density lipoprotein; D020780:Matrix Metalloproteinase 9; D000077288:Troglitazone; D013755:Tetradecanoylphorbol Acetate; D015230:Prostaglandin D2; C039671:ciglitazone