The effect of interleukin 1β 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.