Interleukin 1 stimulates cholesterol esterification and cholesterol deposition in J774 monocytes-macrophages.
The effects of interleukin 1beta (IL1) in the range of concentration of 10-30 ng/ml on cholesterol metabolism were investigated in the monocyte-macrophage cell line J774. IL1 enhanced cholesterol esterification by [14C]oleic acid and acyl-coenzyme A cholesterol acyl transferase activity in a dose-dependent manner. Incubation of IL1-treated cells with acetylated low density lipoproteins labelled with [3H]cholesteryllinoleate resulted in accumulation of radioactive cholesterol in free and esterified form. Concomitantly, IL1 increased the free and esterified cholesterol intracellular content measured by the cholesterol oxidase technique. The effect of IL1 on cholesterol esterification by oleic acid was not observed in the presence of cycloheximide or of the ACAT inhibitor Sandoz 58 035. IL1 also stimulated cholesterol esterification in other cell types such as human fibroblasts and murine endothelial and smooth muscle cells. The effect of IL1 is specific, since IL2 or tumor necrosis factor (TNF) exhibited no significant activity, whereas oncostatin M only slightly enhanced cholesterol esterification. Since cholesterol deposition is involved in the initiation and progression of the atherosclerotic lesions, these findings highlight the role of the inflammatory cytokine IL1 on this process.
Mazière
C
C
Département de Biochimie, Faculté de Médecine Saint-Antoine, Paris, France.
Barbu
V
V
Auclair
M
M
Mazière
J C
JC
D000577:Amides / Q000494:pharmacology; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004951:Esterification; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D053683:Oncostatin M; D017646:Organosilicon Compounds; D010455:Peptides / Q000494:pharmacology; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000577:Amides; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D007376:Interleukin-2; C508351:OSM protein, human; D009829:Oleic Acids; D017646:Organosilicon Compounds; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D053683:Oncostatin M; D019301:Oleic Acid; C040256:SAN 58035; D002784:Cholesterol; D003513:Cycloheximide; D002785:Sterol O-Acyltransferase