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Am J Physiol Endocrinol Metab (October 2, 2007). doi:10.1152/ajpendo.00315.2007
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Submitted on May 22, 2007
Accepted on September 27, 2007

The effects of lycopene on the induction of foam cell formation by modified LDL

Mariarosaria Napolitano1, Clara De Pascale2, Caroline P.D. Wheeler-Jones2, Kathleen M Botham2, and Elena Bravo1*

1 Department of Haematology, Oncology and Molecular Medicine, Istituto Superiore di Sanita', Rome, Italy
2 Department of Veterinary Basic Sciences, Royal Veterinary College, London, United Kingdom

* To whom correspondence should be addressed. E-mail: elena.bravo{at}iss.it.

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)-1{beta} and tumour 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-1{beta}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 down-regulating the activity and expression of SR-A. However, these effects are accompanied impaired secretion of the anti-inflammatory cytokine, IL10, suggesting that it may also have a concomitant pro-inflammatory effect.







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