Gliclazide inhibits differentiation-associated biologic events in human monocyte-derived macrophages.
We investigated the in vitro effect of gliclazide on human monocyte-derived macrophage scavenger receptor expression and activity, foam cell formation, and lipopolysaccharide-induced cytokine production. Differentiation of human monocytes into macrophages in the presence of gliclazide (1-10 microg/mL) decreased CD36 expression by 20% to 50%, with maximal effect occurring at 2.5 microg/mL (P<.05). This effect was mimicked by vitamin E (50 micromol/L) and N-acetyl-L-cysteine (10 mmol/L). Incubation of the cells with gliclazide and N-acetyl-L-cysteine also reduced CD36 activity by 30% (P<.02). Despite these effects, neither gliclazide nor vitamin E did affect foam cell formation. In contrast, gliclazide significantly reduced lipopolysaccharide-stimulated macrophage tumor necrosis factor alpha and interleukin 6 secretion (P<.05). Overall, these data indicate that gliclazide, at concentrations in the therapeutic range, may regulate some key biologic events associated with the process of monocyte differentiation into macrophages.
Mamputu
Jean-Claude
JC
Vascular Immunology Laboratory, CHUM Research Centre, Notre-Dame Hospital, Department of Medicine, University of Montreal, Quebec, Canada H2L 4M1.
Li
Ling
L
Renier
Geneviève
G
D018955:CD36 Antigens / Q000032:analysis; D002454:Cell Differentiation; D002478:Cells, Cultured; D005487:Foam Cells / Q000166:cytology; D005907:Gliclazide / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D051116:Receptors, Scavenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018955:CD36 Antigens; D015850:Interleukin-6; D008070:Lipopolysaccharides; D051116:Receptors, Scavenger; D014409:Tumor Necrosis Factor-alpha; D005907:Gliclazide