abstract
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.
keywords
INFLAMMATION; POLARIZATION; PHENOTYPE; ACTIVATION; PATHWAY; ROLES
subject category
Biochemistry & Molecular Biology; Chemistry
authors
Conde, TA; Mendes, L; Gaspar, VM; Mano, JF; Melo, T; Domingues, MR; Duarte, IF
our authors
Iola Melissa Fernandes Duarte
Principal Researcher
João Mano
Vice Director
Luís Filipe Figueiredo Mendes
PhD Student
Tiago Alexandre Teixeira de Sousa Conde
MSc Student
Vítor Gaspar
Assistant Professoracknowledgements
This work was developed in the scope of the projects CICECO-Aveiro Institute of Materials (Ref. UIDB/50011/2020 & UIDP/50011/2020), LAQV/REQUIMTE (UIDB/50006/2020) and CESAM (UIDB/50017/2020 & UIDP/50017/2020), financed by national funds through the Foundation for Science and Technology (FCT)/MCTES.