Lovastatin induces differentiation of Mono Mac 6 cells.
The proliferation of human monocytic Mono Mac 6 cells was significantly retarded by treatment with lovastatin (LOV, 10 microM) for 72 h. Treatment of Mono Mac 6 cells with LOV increased surface protein expression of monocyte-associated CD14 and the integrin-chain CD11b towards levels found in isolated human blood monocytes. These effects were dose-dependent and completely reversed by the isoprenoid precursor mevalonate (MVA). LOV failed to induce growth retardation and upregulation of CD11b or CD14 in the less mature premonocytic U937 cell line. While CD11b expression was comparable in Mono Mac 6 cells treated with LOV (10 microM), TNF (100 U ml-1) or LPS (10 ng ml-1), upregulation of CD14 by LOV was less pronounced. Basal CD23 expression was unaffected by LOV but markedly reduced by treatment with TNF or LPS. Moreover, LOV enhanced Mono Mac 6 adhesiveness to human umbilical vein endothelial cells to levels found in isolated human blood monocytes, probably due to the increased CD11b and CD14 expression. In conclusion, LOV can induce differentiation of monocytic cells which is reflected by the retardation of growth, expression of CD14 and CD11b, and enhanced adhesiveness.
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Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Ludwig-Maximilians-Universität, München, Germany.
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D000214:Acyl Coenzyme A / Q000037:antagonists & inhibitors; D015415:Biomarkers; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000166:cytology; D004730:Endothelium, Vascular / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008148:Lovastatin / Q000494:pharmacology*; D016177:Macrophage-1 Antigen / Q000187:drug effects; D008798:Mevalonic Acid / Q000378:metabolism; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology
D000214:Acyl Coenzyme A; D015415:Biomarkers; D004791:Enzyme Inhibitors; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D014409:Tumor Necrosis Factor-alpha; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D008148:Lovastatin; D008798:Mevalonic Acid