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

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-γ (PPAR-γ) has been shown to inhibit MMP-9 activity. To evaluate whether ox-LDL, a PPAR-γ activator, inhibits PMA-induced MMP-9 expression and activity, and if so, whether CD36 and PPAR-γ 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 µg/ml) or PPAR-γ activators such as troglitazone (5 µM), ciglitazone (5 µM), and 15d- PGJ2 (1 µM) for 24 h. This ox-LDL or PPAR-γ activator-mediated inhibition of µM P-9 activity was diminished by the pre-treatment of cells with a blocking antibody to CD36, or PGF2a (0.3 µM), which is a PPAR-γ 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-γ.