The effect of interleukin 1 beta on the biosynthesis of cholesterol, phosphatidylcholine, and sphingomyelin in fibroblasts, and on their efflux from cells to lipid-free apolipoprotein A-I.
In this study we have investigated the effect of interleukin 1beta (IL-1beta) on the metabolism of cholesterol and choline-phospholipids in cultured fibroblasts, and also measured efflux of these lipids to lipid-free apo A-I as a function of IL-1beta treatment. Long-term exposure (up to 48 h) of cells to IL-1beta (1 ng.mL-1) markedly increased the rate of cholesterol esterification, as determined by the incorporation of [3H]oleic acid into cholesteryl esters. This treatment also led to a substantially increased mass of cholesteryl esters in the cells. The accumulation of cholesteryl esters in IL-1beta-treated cells could be blocked using compound 58-035 to inhibit the activity of acyl-CoA cholesterol acyl transferase. The activation of cholesterol esterification by IL-1beta was evident within a few hours after initiation of the IL-1beta treatment. Cholesterol biosynthesis was inhibited by 25% by IL-1beta (after 48 h exposure), and this eventually led to a 20% decrease in cell cholesterol mass. Treatment of cells with IL-1beta for 48 h also reduced the synthesis of sphingomyelin and caused a 30% decrease in cell sphingomyelin mass (after 48 h at 1 ng.mL-1 of IL-1beta). IL-1beta did not stimulate an acute (within a few minutes up to an hour) degradation of cell [3H]sphingomyelin. This suggests that IL-1beta did not activate an endogenous sphingomyelinase in these cells, but only affected rates of synthesis. The rate of phosphatidylcholine synthesis was barely affected, but mass was moderately reduced by a 48-h treatment of cells with IL-1beta. Finally, the efflux of cell [3H]cholesterol, [3H]sphingomyelin, and [3H]phosphatidylcholine to lipid-free apolipoprotein A-I was markedly increased from cells treated with IL-1beta for 24 and 48 h. We conclude that long-term exposure of cells to IL-1beta had marked effects on the cellular homeostasis of cholesterol and choline-containing phospholipids.
Department of Biochemistry and Pharmacy, Abo Akademi University, Turku, Finland.
R
R
Kronqvist
P
P
Leppimäki
P
P
Mehto
J P
JP
Slotte
D016632:Apolipoprotein A-I / Q000378:metabolism; D001693:Biological Transport, Active / Q000187:drug effects; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000378:metabolism*; D012867:Skin / Q000166:cytology; D013109:Sphingomyelins / Q000378:metabolism*
D016632:Apolipoprotein A-I; D002788:Cholesterol Esters; D007375:Interleukin-1; D010713:Phosphatidylcholines; D013109:Sphingomyelins