Ox-LDL suppresses PMA-induced MMP-9 expression and activity through CD36-mediated activation of PPAR-γ

During chronic inflamatory response, mono- cytes/macrophages produce 92-kDa matrix meta-loproteinase-9 (MP-9), which may contribute to their extravasation, migration and tissue re-modeling. Activation of peroxisome proliferator- activated factor receptor-γ (PPAR-γ) has been shown to inhibit MMP-9 activity. To evaluate whether ox-LDL, a PAR-γ activator, inhibits PMA-induced MP-9 expresion and activity, and if so, whether CD36 and PPAR-γ are in-fect of ox-LDL on MMP-9 expresion and activity in PMA-activated human monocytic cell line U937. PMA-induced MMP-9 expresion and ac-tivity were supressed by the treatment with ox-LDL (50 g/ml) or PPAR-γ activators such as troglitazone (5 M), ciglitazone (5 M), and 15d- PGJ2 (1 M) for 24 h. This ox-LDL or PPAR-γ activator-mediated inhibition of MP-9 activity was diminished by the pre-treatment of cels with a blocking antibody to CD36, or PGF2α (0.3 M), which is a PPAR-γ inhibitor, as wel as overexpresion of a dominant-negative form of CD36. Taken together, these results sugest that ox-LDL suppresses PMA-induced MMP-9 ex-presion and activity through CD36-mediated activation of PAR-γ. KCI Citation Count: 20