Abstract
The postprandial phase is characterized by the circulation of atherogenic dietary-triacylglycerol rich lipoproteins. Little is known about the modulation of lipid and immune functions in macrophages by these particles or of the role of the oxysterols found in food such as 7beta-hydroxycholesterol and 7-ketocholesterol. Human macrophages were tested with different concentrations of chylomicron remnant-like particles (CRLP) with or without incorporated oxysterols to study their uptake by the cells, and their effects on cholesteryl ester and triacylglycerol synthesis and the secretion of inflammatory mediators, including tumour necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6) and interleukin 10 (IL-10). Independently of the presence of oxysterols, CRLP caused cholesterol accumulation. However, the dose-dependent increase in [3H]cholesterol internalization by macrophages after incubation with [3H]cholesteryl ester-labelled CRLP was abolished by the presence of oxysterols in the particles. TNF-alpha secretion was decreased and that of IL-10 unaffected by CRLP independently of the presence of oxysterol. Exposure to CRLP containing 7beta-hydroxysterol, but not to CRLP or 7-ketosterol-containing CRLP, reduced IL-6 secretion with respect to cells not exposed to any particles. Because TNF-alpha levels have been related to scavenger receptor expression, we tested the uptake of modified LDL in macrophages exposed to human postprandial triacylglycerol-rich lipoproteins and found it to be markedly increased. Cholesterol loading as a result of dietary lipids depresses the inflammatory response of macrophages and the presence of 7beta-hydroxysterol may exacerbate this effect. In addition, exposure to dietary lipids enhances scavenger receptor activity in macrophages. These results suggest that changes induced by dietary lipids in human macrophage function are related to an increased propensity of the cells to accumulate lipids during the postprandial phase.
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