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Published on: October 17, 2017
Effects of lycopene on the induction of foam cell formation by modified LDL
Mariarosaria Napolitano1, Clara De Pascale, Caroline Wheeler-Jones
1Istituto Superiore di Sanitá, Dept. of Haematology, Oncology and Molecular Medicine, Viale Regina Elena 299, 00161 Rome, Italy.
Abstract:
The effect of lycopene on macrophage foam cell formation induced by modified low-density lipoprotein (LDL) was studied. Human monocyte-derived macrophages (HMDM) were incubated with lycopene in the presence or absence of native LDL (nLDL) or LDL modified by oxidation (oxLDL), aggregation (aggLDL), or acetylation (acLDL). The cholesterol content, lipid synthesis, scavenger receptor activity, and the secretion of inflammatory [interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha] and anti-inflammatory (IL-10) cytokines was determined. Lycopene was found to decrease the synthesis of cholesterol ester in incubations without LDL or with oxLDL while triacylglycerol synthesis was reduced in the presence of oxLDL and aggLDL. Scavenger receptor activity as assessed by the uptake of acLDL was decreased by approximately 30% by lycopene. In addition, lycopene inhibited IL-10 secretion by up to 74% regardless of the presence of nLDL or aggLDL but did not affect IL-1beta or TNF-alpha release. Lycopene also reduced the relative abundance of mRNA transcripts for scavenger receptor A (SR-A) in THP-1 macrophages treated with aggLDL. These findings suggest that lycopene may reduce macrophage foam cell formation induced by modified LDL by decreasing lipid synthesis and downregulating the activity and expression of SR-A. However, these effects are accompanied by impaired secretion of the anti-inflammatory cytokine IL-10, suggesting that lycopene may also exert a concomitant proinflammatory effect.
Insights
Lycopene may reduce macrophage foam cell formation by decreasing lipid synthesis and scavenger receptor activity. However, it also impairs anti-inflammatory cytokine secretion, suggesting a potential proinflammatory effect.
Area of Science:
- Nutritional Science
- Cell Biology
- Immunology
Background:
- Macrophage foam cell formation is a key process in atherosclerosis.
- Modified low-density lipoprotein (LDL) plays a critical role in inducing foam cell formation.
- Lycopene's potential effects on this process require further investigation.
Purpose of the Study:
- To investigate the impact of lycopene on macrophage foam cell formation induced by various modified LDL particles.
- To determine lycopene's effects on lipid synthesis, cholesterol metabolism, and cytokine secretion in macrophages.
Main Methods:
- Human monocyte-derived macrophages (HMDM) were incubated with lycopene and different forms of LDL (native, oxidized, aggregated, acetylated).
- Measurements included cholesterol content, lipid synthesis, scavenger receptor activity (acLDL uptake), and cytokine secretion (IL-1beta, TNF-alpha, IL-10).
- mRNA expression of scavenger receptor A (SR-A) was analyzed in THP-1 macrophages.
Main Results:
- Lycopene decreased cholesterol ester synthesis (without LDL or with oxLDL) and triacylglycerol synthesis (with oxLDL and aggLDL).
- Lycopene reduced scavenger receptor activity (acLDL uptake) by ~30% and SR-A mRNA expression.
- Lycopene inhibited IL-10 secretion but did not affect IL-1beta or TNF-alpha release.
Conclusions:
- Lycopene may mitigate modified LDL-induced macrophage foam cell formation by reducing lipid synthesis and downregulating SR-A.
- However, lycopene's inhibition of anti-inflammatory IL-10 suggests a potential dual effect, possibly including a proinflammatory component.
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