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 1 beta (IL-1 b eta) 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-1 beta treatment. Long-term exposure (up to 48 h) of cells to IL-1 beta (1 ng . mL(-1)) markedly increased the rate of cholester ol esterification, as determined by the incorporation of [H-3]oleic acid in to cholesteryl esters. This treatment also led to a substantially increased mass of cholesteryl esters in the cells. The accumulation of cholesteryl e sters in IL-1 beta-treated cells could be blocked using compound 58-035 to inhibit the activity of acyl-CoA cholesterol acyl transferase. The activati on of cholesterol esterification by IL-1 beta was evident within a few hour s after initiation of the IL-1 beta treatment. Cholesterol biosynthesis was inhibited by 25% by IL-1 beta (after 48 h exposure), and this eventually l ed to a 20%, decrease in cell cholesterol mass. Treatment of cells with IL- 1 beta 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-1 beta). IL-1 beta did not stimulate an acute (within a few minutes up to an hour) degradation of cell [H-3]sphingomyelin. This suggests that IL-1 beta did not activate an endogenous sphingomyelinase in these cells, but only af fected rates of synthesis, The rate of phosphatidylcholine synthesis was ba rely affected, but mass was moderately reduced by a 48-h treatment of cells with IL-1 beta. Finally, the efflux of cell [H-3]cholesterol, [H-3]sphingo myelin, and [H-3]phosphatidylcholine to lipid-free apolipoprotein A-I was m arkedly increased from cells treated with IL-1 beta for 24 and 48 h. We con clude that long-term exposure of cells to IL-1 beta had marked effects on t he cellular homeostasis of cholesterol and choline-containing phospholipids .