Lipid metabolism and TNF-alpha secretion in response to dietary sterols in human monocyte derived macrophages (original) (raw)
Experimental Biology and Medicine, 2013
The potential link between the inflammatory effects of postprandial lipemia and the induction of macrophage foam cell formation by triacylglycerol-rich lipoproteins (TGRL) was studied using postprandial triacylglycerol-rich lipoproteins ( ppTGRL) derived from human volunteers and primary human monocyte-derived macrophages (HMDM). Subjects were fed a test meal high in dairy fat, followed three hours later by isolation of serum ppTGRL. Pro-inflammatory (M1) and antiinflammatory (M2) phenotypes were induced in HMDM by treatment with lipopolysaccharide (LPS) or dexamethasone (DEX), respectively. ppTGRL caused a dose-dependent increase in both triacylglycerol (TG) and cholesterol (CH) accumulation in the cells. TG accumulation was unaffected by LPS or DEX treatment, but LPS as compared with DEXtreated HMDM were found to accumulate more CH, and this effect was greater than that induced by ppTGRL in untreated cells. LPS-treatment had no effect on lipid uptake from ppTGRL (via the LDLr, scavenger receptors or SR-B1) or on CH efflux, but the CH synthesis inhibitor mevinolin abolished the difference between CH accumulation in LPS-and DEX-treated cells, suggesting that CH synthesis is enhanced in the inflammatory state. Phospholipid (PL) synthesis was increased in inflammatory M1 as compared with anti-inflammatory M2 HMDM. Moreover, TG synthesis was decreased by ppTGRL in DEX-treated as compared with untreated cells. We conclude, therefore, inflammation causes a greater increase in the accumulation of neutral lipids than ppTGRL in macrophages, and that this effect is related to modulation of PL metabolism and possibly also CH synthesis. Thus, the inflammatory phenotype of macrophages influences their lipid metabolism, and is, therefore, likely to modulate the induction of macrophage lipid accumulation by lipoproteins associated with foam cell formation.
Experimental Biology and Medicine, 2004
The effects of low-density lipoprotein (LDL) and chylomicron remnants on lipid accumulation in human monocyte-derived macrophages (HMDMs) and in macrophages derived from the human monocyte cell line THP-1 were compared. The HMDMs or THP-1 macrophages were incubated with LDL, oxidized LDL (oxLDL), chylomicron remnant-like particles (CMR-LPs), or oxidized CMR-LPs (oxCMR-LPs), and the amount and type of lipid accumulated were determined. As expected, the lipid content of both cell types was increased markedly by oxLDL but not LDL, and this was due to a rise in cholesterol, cholesteryl ester (CE), and triacylglycerol (TG) levels. In contrast, both CMR-LPs and oxCMR-LPs caused a considerable increase in cellular lipid in HMDMs and THP-1 macrophages, but in this case there was a greater rise in the TG than in the cholesterol or CE content. Lipid accumulation in response to oxLDL, CMR-LPs, and oxCMR-LPs was prevented by the ACAT inhibitor CI976 in HMDMs but not in THP-1 macrophages, where TG levels remained markedly elevated. The rate of incorporation of [ 3 H]oleate into CE and TG in THP-1 macrophages was increased by oxLDL, CMR-LPs, and oxCMR-LPs, but incorporation into TG was increased to a greater extent with CMR-LPs and oxCMR-LPs compared with oxLDL. These results demonstrate that both CMR-LPs and oxCMR-LPs cause lipid accumulation in human macrophages comparable to that seen with oxLDL and that oxidation of the remnant particles does not enhance this effect. They also demonstrate that a greater proportion of the lipid accumulated in response to CMR-LPs compared with oxLDL is TG rather than cholesterol or CE and that this is associated with a higher rate of TG synthesis. This study, therefore, provides further evidence to suggest that chylomicron remnants have a role in foam cell formation that is distinct from that of oxLDL.
Exogenously Added Oxyphytosterols Do Not Affect Macrophage-Mediated Inflammatory Responses
Lipids
Although phytosterols, plant-derived sterol-like components, are well known for their cholesterol-lowering properties, their atherogenic potential is still under debate. Although they are known to share structural similarities with cholesterol, it is unclear whether their oxidized forms (oxyphytosterols) have the capacity to mediate proinflammatory responses in macrophages. In the present study, bone marrow-derived macrophages were treated with oxidized low-density lipoproteins, oxyphytosterols (7keto-sito/ campesterol [7keto-sit/camp] or 7-beta-hydroxy-sito/campesterol [7βOH-sit/camp]), nonoxidized phytosterol (β-sitosterol), or carrier-control (cyclodextrin) in a doseand time-dependent manner. Inflammatory cytokine release, activity, and the corresponding mRNA expression levels were analyzed. 7βOH-sit/camp, rather than 7keto-sit/camp, induced a modest proinflammatory response in wild-type cells derived from C57Bl/6 mice. The observed mild inflammatory effects are independent of the low-density lipoprotein receptor and Cluster of differentiation 36/Scavenger receptor-a. These data suggest that exogenously added oxyphytosterols do not affect macrophage-mediated inflammatory responses, at least in vitro.
Data in Brief, 2016
This article supports experimental evidence on the timedependent effect on gene expression related to inflammation and cholesterol deposition in lipid-loaded cells. The cells employed were human monocytes THP1 line transformed into macrophages by treatment with phorbol esters. Macrophages were treated at different times with oxidized low density lipoprotein (Ox-LDL) and then gene expression was measured. We also include data about the different types of oxidized lipoprotein obtained (low, media or high oxidation) for differential exposure with Cu ions. These data include characterization to lipid and protein peroxidative damage and also quantification of cell viability by exposure to native and modified LDL. The present article complements data published in "Decreased OxLDL uptake and cholesterol efflux in THP1 cells elicited by cortisol and by cortisone through 11β-hydroxysteroid dehydrogenase type 1" Ledda et al.
British Journal of Nutrition, 2009
Dietary long-chain PUFA, both n-3 and n-6, have unique benefits with respect to CVD risk. The aim of the present study was to determine the mechanisms by which n-3 PUFA (EPA, DHA) and n-6 PUFA (linoleic acid (LA), arachidonic acid (AA)) relative to SFA (myristic acid (MA), palmitic acid (PA)) alter markers of inflammation and cholesterol accumulation in macrophages (MΦ). Cells treated with AA and EPA elicited significantly less inflammatory response than control cells or those treated with MA, PA and LA, with intermediate effects for DHA, as indicated by lower levels of mRNA and secretion of TNFα, IL-6 and monocyte chemoattractant protein-1. Differences in cholesterol accumulation after exposure to minimally modified LDL were modest. AA and EPA resulted in significantly lower MΦ scavenger receptor 1 mRNA levels relative to control or MA-, PA-, LA-and DHA-treated cells, and ATP-binding cassette A1 mRNA levels relative to control or MA-, PA-and LA-treated cells. These data suggest changes in the rate of bidirectional cellular cholesterol flux. In summary, individual long-chain PUFA have differential effects on inflammatory response and markers of cholesterol flux in MΦ which are not related to the n position of the first double bond, chain length or degree of saturation.
Biochimica et biophysica acta, 1987
We have previously shown that cultured rat alveolar macrophages synthesize and secrete lipoprotein lipase into the medium. The purpose of the present experiments is to examine whether cholesterol-enriched lipoproteins from cholesterol-fed animals have any effects on the lipoprotein lipase secretion and the lipid accumulation in macrophages. Macrophages incubated with the VLDL obtained from rats fed a normal diet secreted 2-fold higher amounts of lipoprotein lipase than those without lipoproteins. Intermediate-, low- and very-low-density lipoproteins from rats fed a high-cholesterol diet also enhanced the lipoprotein lipase secretion. Normal high- and low-density lipoproteins, and high-density lipoproteins from hypercholesterolemic animals did not cause any increase in the lipoprotein lipase secretion. The lipoproteins which stimulated the lipoprotein lipase secretion caused intracellular accumulation of both triacylglycerol and cholesterol. It is speculated that macrophages residing...
FEBS …, 2006
The first visible lesions in atherosclerosis development are fatty streaks, which are formed when macrophages that have invaded the artery wall take up lipid from plasma lipoproteins in the subendothelial space and become so engorged that they form foam cells . It is known that low-density lipoprotein (LDL) has a major role in the induction of foam cell formation, but it is also clear that oxidation of the LDL particles, a pro-cess that can occur within the artery wall, is necessary before extensive lipid accumulation occurs . Recent work in our laboratory and others, however, has provided strong evidence that chylomicron remnants, the lipoproteins that carry fat and cholesterol from the diet, are also able to induce macrophages to form foam cells, and furthermore, that prior oxidation of the particles is not required for their effect .
2007
Background: Plasma HDL concentrations and composition, important predictors of coronary heart disease, are modified by fatty acids (FAs) in high-fat diets. Objective: Following the National Cholesterol Education Program Adult Treatment Panel III recommendation that 25%-30% of total calorie intake be in the form of fat, we compared the results of the intake of 30% of energy as fat in diets enriched with trans, polyunsaturated, or saturated FAs. These dietary effects on the composition and ability of HDL 2 , HDL 3 , and total plasma to efflux cholesterol from mouse peritoneal macrophages that previously were loaded with LDL-acetylated 14C-cholesteryl ester were evaluated by using ultracentrifugally isolated lipoproteins. Design: After a 2-wk run-in period, 30 healthy persons (9 M, 21 F), were randomly distributed among 3 groups (n ҃ 10/group) and fed for 4 wk with either an 8.3% trans FA, a 14.6% polyunsaturated FA, or a 13.2% saturated FA diet. The 3 diets had similar proportions of monounsaturated FAs. Results: The percentage of radioactive cell cholesterol removal did not vary among these diets, possibly because of the small difference in the composition of the HDL fraction elicited by the different diets. However, the percentage was consistently higher for HDL 3 than for HDL 2 . Conclusion: Differences in the cell cholesterol efflux with these diets were not observed, probably because the changes in the HDL composition were quite modest as a result of the limitation of the fat intake to 30% of total calories and because of the rigorous control of the proportions of FAs in the experimental diets used in this investigation.
Clinical Science, 2001
The effects of native and oxidized chylomicron remnants on the synthesis of cholesteryl ester and triacylglycerol in macrophages, and the way that this is influenced by exposure of the cells to oestrogen, was investigated using the human monocyte cell line THP-1 and chylomicronremnant-like particles containing human apolipoprotein E (CRLPs). Synthesis of the lipids was measured by the incorporation of [ 3 H]oleate into cholesteryl ester and triacylglycerol. CRLPs (5-40 µg of cholesterol/ml) containing either trilinolein or triolein as the triacylglycerol component caused a dose-dependent decrease in cholesteryl ester formation, while triacylglycerol production was unchanged. After oxidation of the CRLPs, the level of thiobarbituric acid-reactive substances was increased by 6.3-fold and 2.2-fold in particles containing trilinolein and triolein respectively. Furthermore, CRLPs containing oxidized trilinolein lost their ability to down-regulate cholesterol esterification, while CRLPs containing oxidized triolein did not. Both types of oxidized CRLPs decreased triacylglycerol synthesis. Treatment of the macrophages with 17β-oestradiol caused increases of approx. 94 % and 34 % in the synthesis of cholesteryl ester and triacylglycerol respectively in the absence of CRLPs. The differences between control and oestrogen-treated cells were abolished, however, when CRLPs (40 µg of cholesterol/ml) were added to the incubations. In addition, in contrast with their lack of effect in control cells, CRLPs containing oxidized trilinolein decreased cholesterol esterification in oestrogen-treated cells by approx. 48 %. These findings with CRLPs suggest that chylomicron remnants have significant effects on cholesteryl ester and triacylglycerol synthesis in macrophages, which may be modulated both by the oxidation state of the particles and by oestrogen.