Napolitano Mariarosaria, De Pascale Clara, Wheeler-Jones Caroline, Botham Kathleen M, Bravo Elena
Istituto Superiore di Sanitá, Dept. of Haematology, Oncology and Molecular Medicine, Viale Regina Elena 299, 00161 Rome, Italy.
Am J Physiol Endocrinol Metab. 2007 Dec;293(6):E1820-7. doi: 10.1152/ajpendo.00315.2007. Epub 2007 Oct 2.
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.
研究了番茄红素对修饰的低密度脂蛋白(LDL)诱导的巨噬细胞泡沫细胞形成的影响。将人单核细胞衍生的巨噬细胞(HMDM)与番茄红素一起孵育,同时存在或不存在天然LDL(nLDL)或经氧化(oxLDL)、聚集(aggLDL)或乙酰化(acLDL)修饰的LDL。测定了胆固醇含量、脂质合成、清道夫受体活性以及炎症性(白细胞介素(IL)-1β和肿瘤坏死因子(TNF)-α)和抗炎性(IL-10)细胞因子的分泌。发现番茄红素在无LDL或有oxLDL的孵育中可降低胆固醇酯的合成,而在oxLDL和aggLDL存在时三酰甘油合成减少。番茄红素使通过acLDL摄取评估的清道夫受体活性降低约30%。此外,无论nLDL或aggLDL是否存在,番茄红素均可将IL-10分泌抑制高达74%,但不影响IL-1β或TNF-α的释放。番茄红素还降低了用aggLDL处理的THP-1巨噬细胞中清道夫受体A(SR-A)mRNA转录本的相对丰度。这些发现表明,番茄红素可能通过减少脂质合成以及下调SR-A的活性和表达来减少修饰的LDL诱导的巨噬细胞泡沫细胞形成。然而,这些作用伴随着抗炎细胞因子IL-10分泌受损,提示番茄红素可能也会产生伴随的促炎作用。