Effects of lycopene on the induction of foam cell formation by modified LDL.
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.
Napolitano
Mariarosaria
M
Istituto Superiore di Sanitá, Dept. of Haematology, Oncology and Molecular Medicine, Viale Regina Elena 299, 00161 Rome, Italy.
De Pascale
Clara
C
Wheeler-Jones
Caroline
C
Botham
Kathleen M
KM
Bravo
Elena
E
D018955:CD36 Antigens / Q000235:genetics; D002338:Carotenoids / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D005487:Foam Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology*; D000077276:Lycopene; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051116:Receptors, Scavenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051117:Scavenger Receptors, Class A / Q000235:genetics; D051122:Scavenger Receptors, Class B / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018955:CD36 Antigens; D002788:Cholesterol Esters; D053583:Interleukin-1beta; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; C032629:acetyl-LDL; C099252:oxidized low density lipoprotein; D016753:Interleukin-10; D002338:Carotenoids; D002784:Cholesterol; D000077276:Lycopene