Differential Modulation of the Phospholipidome of Proinflammatory Human Macrophages by the Flavonoids Quercetin, Naringin and Naringenin
Differential Modulation of the Phospholipidome of Proinflammatory Human Macrophages by the Flavonoids Quercetin, Naringin and Naringenin
复制标题
DOI：
10.3390/molecules25153460
复制
发表时间：
2020-08-01
期刊：
影响因子：
4.6
通讯作者：
Duarte, Iola F.
中科院分区：
文献类型：
--
作者：
Conde, Tiago A.;Mendes, Luis;Duarte, Iola F.
黄酮类化合物的免疫调节活性日益受到重视。巨噬细胞磷脂(Pls)在细胞介导的炎症反应中起重要作用。然而，关于类黄酮类药物对这些pls的影响，我们知之甚少。在这项工作中，我们使用基于质谱学的脂类组学来表征促炎症的人巨噬细胞样细胞(THP-1来源的和内毒素+干扰素-γ刺激的)在三种非细胞毒性浓度的黄酮类化合物：栎素、柚皮苷和柚皮苷元孵育后磷脂体的变化。共鉴定出不同类别的147种磷酸盐，并测定了它们的相对丰度。每种黄酮类化合物都有其独特的诱导效应特征。槲皮素的影响最大，既作用于构成成分的磷脂酰胆碱、磷脂酰乙醇胺和鞘磷脂，也作用于次要的信号脂类，如磷脂酰肌醇(PI)和磷脂酰丝氨酸(PS)。相反，柚皮苷几乎不影响pls的结构，导致信号分子的变化，而这些变化与槲皮素处理的巨噬细胞中看到的相反。反过来，尽管与槲皮素有相同的作用，但柚皮苷并不改变PI和PS水平，并干扰一组不同于Qercetin调节的磷脂酰胆碱。这些结果表明，黄酮类化合物的生物活性涉及巨噬细胞磷脂体的深刻和特异的重塑，为进一步研究细胞磷脂在类黄酮介导的免疫调节作用中的作用铺平了道路。
The immunomodulatory activity of flavonoids is increasingly appreciated. Macrophage phospholipids (PLs) play crucial roles in cell-mediated inflammatory responses. However, little is known on how these PLs are affected upon flavonoid treatment. In this work, we have used mass-spectrometry-based lipidomics to characterize the changes in the phospholipidome of proinflammatory human-macrophage-like cells (THP-1-derived and LPS+IFN-gamma-stimulated) incubated with non-cytotoxic concentrations of three flavonoids: quercetin, naringin and naringenin. One hundred forty-seven PL species belonging to various classes were identified, and their relative abundances were determined. Each flavonoid displayed its own unique signature of induced effects. Quercetin produced the strongest impact, acting both on constitutive PLs (phosphatidylcholines, phosphatidylethanolamines and sphingomyelins) and on minor signaling lipids, such as phosphatidylinositol (PI) and phosphatidylserine (PS) species. Conversely, naringin hardly affected structural PLs, producing changes in signaling molecules that were opposite to those seen in quercetin-treated macrophages. In turn, albeit sharing some effects with quercetin, naringenin did not change PI and PS levels and interfered with a set of phosphatidylcholines distinct from those modulated by quercetin. These results demonstrate that flavonoids bioactivity involves profound and specific remodeling of macrophage phospholipidome, paving the way to future studies on the role of cellular phospholipids in flavonoid-mediated immunomodulatory effects.