Related Experiment Video
Updated: Jul 25, 2026
An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
Ox-LDL suppresses PMA-induced MMP-9 expression and activity through CD36-mediated activation of PPAR-g
Kyoung Jin Lee1, Hyun A Kim, Pyeung Hyeun Kim
1Vascular System Research Center, Department of Anatomy and Cell Biology, College of Medicine, Kangwon National University, Chunchon 200-701, Korea.
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-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.
Insights
Oxidized low-density lipoprotein (ox-LDL) inhibits matrix metalloproteinase-9 (MMP-9) in inflammatory responses. This effect is mediated by CD36-activated peroxisome proliferator-activated receptor gamma (PPAR-γ), impacting monocyte migration and tissue remodeling.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- Monocytes/macrophages produce matrix metalloproteinase-9 (MMP-9) during chronic inflammation, contributing to cell migration and tissue remodeling.
- Activation of peroxisome proliferator-activated receptor gamma (PPAR-γ) is known to inhibit MMP-9 activity.
Purpose of the Study:
- To investigate if oxidized low-density lipoprotein (ox-LDL), a PPAR-γ activator, inhibits phorbol 12-myristate 13-acetate (PMA)-induced MMP-9 expression and activity.
- To determine the involvement of CD36 and PPAR-γ in the inhibitory effect of ox-LDL on MMP-9.
Main Methods:
- Human monocytic cell line U937 were activated with PMA and treated with ox-LDL or known PPAR-γ activators (troglitazone, ciglitazone, 15d-PGJ2).
- MMP-9 expression and activity were assessed.
- Cells were pre-treated with CD36 blocking antibody, a PPAR-γ inhibitor (PGF2α), or overexpressed dominant-negative CD36 to evaluate the mechanism.
Main Results:
- Ox-LDL and PPAR-γ activators significantly suppressed PMA-induced MMP-9 expression and activity.
- The inhibitory effect of ox-LDL and PPAR-γ activators on MMP-9 was reduced by CD36 blockade, PPAR-γ inhibition, or dominant-negative CD36.
- These findings indicate a role for CD36 in mediating the inhibitory effects.
Conclusions:
- Oxidized low-density lipoprotein (ox-LDL) suppresses PMA-induced matrix metalloproteinase-9 (MMP-9) expression and activity in human monocytes.
- The mechanism involves the CD36-mediated activation of peroxisome proliferator-activated receptor gamma (PPAR-γ).
- This pathway may represent a therapeutic target for inflammatory conditions involving MMP-9.
