Aged garlic extract inhibits CD36 expression in human macrophages via modulation of the PPARgamma pathway.
Expression of CD36 scavenger receptors on macrophages is involved in oxidized low-density lipoprotein uptake and foam cell formation during atherosclerotic lesion development. We examined the effects of aged garlic extract (AGE), a garlic preparation enriched in water-soluble cysteinyl moieties that increases cellular total thiols and glutathione concentrations, on CD36 expression in human monocytes/macrophages (THP-1 cells and primary human monocytes). Compared to control, AGE (1-5 mg/mL) dose-dependently and significantly suppressed CD36 expression up to by 61.8 +/- 7.4% in THP-1-derived macrophages and up to 50.5 +/- 7.1% in primary human macrophages, respectively. Furthermore, AGE prevented induction of CD36 expression by the peroxisome proliferator activator receptor (PPAR) gamma agonist troglitazone, and decreased binding of nuclear proteins to a PPARgamma response element. AGE showed a stronger inhibitory effect on CD36 expression in THP-1 cells during simultaneous incubation with phorbol 12-myristate 13-acetate (PMA) compared to cells that had been pre-incubated with PMA. Furthermore, AGE decreased CD11b expression in a dose-dependent manner. These data indicate that AGE inhibits CD36 expression by modulating the PPARgamma pathway in human macrophages and monocytes differentiation into macrophages, and suggests that the extract could be useful for the prevention of atherosclerotic lesions.
Morihara
Naoaki
N
Center for Vascular Medicine, Section Angiology, Medical Policlinic, University of Munich Medical Center, Pettenkoferstrasse 8A, D-80336 Munich, Germany.
Ide
Nagatoshi
N
Weiss
Norbert
N
D050197:Atherosclerosis / Q000517:prevention & control*; D018955:CD36 Antigens / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D004353:Drug Evaluation, Preclinical; D005737:Garlic; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects; D047495:PPAR gamma / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use
D018955:CD36 Antigens; D047495:PPAR gamma; D010936:Plant Extracts