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.
Subject(s)
Humans , Antibodies, Blocking/pharmacology , CD36 Antigens/immunology , Cells, Cultured , Chromans/pharmacology , Matrix Metalloproteinase 9/antagonists & inhibitors , Lipoproteins, LDL/pharmacology , Monocytes/drug effects , NF-kappa B/antagonists & inhibitors , PPAR gamma/metabolism , Prostaglandin D2/analogs & derivatives , RNA, Messenger/analysis , Tetradecanoylphorbol Acetate/antagonists & inhibitors , Thiazolidinediones/pharmacology , Transcription, Genetic/drug effectsABSTRACT
The ability of Plasmodium falciparum infected erythrocytes from 162 Thai patients with uncomplicated malaria, 82 patients with severe malaria and 19 patients with cerebral malaria to form rosettes in vitro was studied. Of 263 isolates, 62 were evaluated for their adherence to different target molecules. We found that wide variation occurred in isolates from all groups in the level of rosette formation and adherence to CD36, intracellular adhesion molecule-1, thrombospondin and chondroitin sulfate A. No statistically significant correlation between the magnitude of rosette formation and disease severity was found (p > 0.05). In addition, our results from the use of purified CD36 as an adherence receptor showed no association between the degree rosetting and level of cytoadherence (p > 0.05, r = -0.04). Our data provide evidence that rosette formation and cytoadherence involve different molecular mechanisms and both phenomena can occur in all manifestations of the disease.