Differential Modulation of the Phospholipidome of Proinflammatory Human Macrophages by the Flavonoids Quercetin, Naringin and Naringenin

摘要

The immunomodulatory activity of flavonoids is increasingly appreciated. Macrophagephospholipids (PLs) play crucial roles in cell-mediated inflammatory responses. However, littleis known on how these PLs are affected upon flavonoid treatment. In this work, we haveused mass-spectrometry-based lipidomics to characterize the changes in the phospholipidomeof proinflammatory human-macrophage-like cells (THP-1-derived and LPS+IFN- γ -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 theirrelative abundances were determined. Each flavonoid displayed its own unique signatureof induced effects. Quercetin produced the strongest impact, acting both on constitutivePLs (phosphatidylcholines, phosphatidylethanolamines and sphingomyelins) and on minorsignaling lipids, such as phosphatidylinositol (PI) and phosphatidylserine (PS) species. Conversely,naringin hardly affected structural PLs, producing changes in signaling molecules that were oppositeto 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 distinctfrom those modulated by quercetin. These results demonstrate that flavonoids bioactivity involvesprofound and specific remodeling of macrophage phospholipidome, paving the way to future studieson the role of cellular phospholipids in flavonoid-mediated immunomodulatory effects.