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

Ziegelhoeffer A.; De Jong J.W.; Ferrari R.; Turi Nagy L.

Febs Journal 262(3): 939-946

1999


ISSN/ISBN: 1742-464X
DOI: 10.1046/j.1432-1327.1999.00484.x
Accession: 062842952

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Abstract
In this study we have investigated the effect of interleukin 1β (IL-1β) 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-1β treatment. Long-term exposure (up to 48h) of cells to IL-1β (1ng·m L−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-1β-treated cells could be blocked using compound 58-035 to inhibit the activity of acyl-Co A cholesterol acyl transferase. The activation of cholesterol esterification by IL-1β was evident within a few hours after initiation of the IL-1β treatment. Cholesterol biosynthesis was inhibited by 25% by IL-1β (after 48h exposure), and this eventually led to a 20% decrease in cell cholesterol mass. Treatment of cells with IL-1β for 48h also reduced the synthesis of sphingomyelin and caused a 30% decrease in cell sphingomyelin mass (after 48h at 1ng·m L−1 of IL-1β). IL-1β did not stimulate an acute (within a few minutes up to an hour) degradation of cell [3H]sphingomyelin. This suggests that IL-1β 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-1β. 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-1β for 24 and 48h. We conclude that long-term exposure of cells to IL-1β had marked effects on the cellular homeostasis of cholesterol and choline-containing phospholipids.