Olive Oil Phenolics Prevent Oxysterol-Induced Proinflammatory Cytokine Secretion and Reactive Oxygen Species Production in Human Peripheral Blood Mononuclear Cells, Through Modulation of p38 and JNK Pathways.

Gessica Serra,Monica Deiana,Jeremy P E Spencer,Giulia Corona

doi:10.1002/mnfr.201700283

Abstract

ScopeThe aim of the present study was to investigate the ability of extra virgin olive oil (EVOO) polyphenols to counteract the proinflammatory effects induced by dietary and endogenous oxysterols in ex vivo immune cells.Methods and resultsPeripheral blood mononuclear cells (PBMCs), separated from the whole blood of healthy donors, were utilized and were stimulated with an oxysterols mixture, in the presence of physiologically relevant concentrations of the EVOO polyphenols, hydroxytyrosol, tyrosol, and homovanillic alcohol. Oxysterols significantly increased the production of proinflammatory cytokines, interleukin‐1β, regulated on activation, normal T‐cell expressed and secreted and macrophage migration inhibitory factor in ex vivo cultured PBMCs. Increased levels of reactive oxygen species (ROS) were also detected along with increased phosphorylation of the p38 and JNK. All phenolic compounds significantly reduced cytokine secretion induced by the oxysterols and inhibited ROS production and mitogen activated protein kinase phosphorylation.ConclusionsThese results suggest that extra virgin olive oil polyphenols modulate the immune response induced by dietary and endogenous cholesterol oxidation products in human immune cells and may hold benefit in controlling chronic immune and/or inflammatory processes.

Highlights

Oxysterols are 27-carbon-atom molecules resulting from non-enzymatic or enzymatic oxidation of cholesterol and have been detected in plasma and tissues due to endogenous formation and dietary intake [1,2,3]
The levels of 3 selected cytokines (IL-1β, migration inhibitory factor (MIF) and RANTES) were further subjected to quantitative analysis, which indicated that a 24h exposure of Peripheral blood mononuclear cells (PBMCs) to oxysterols (20 μM) resulted in a significant increase in the secretion of the pro-inflammatory cytokines/chemokines, IL-1β (Fig.1A), MIF (Fig.1B) and RANTES (Fig.1C) in PBMCs
Pre-treatment with HT, TYR and homovanillic alcohol (HVA) (0.25, 0.5, μM), significantly reduced the secretion of pro-inflammatory cytokines/chemokines induced by the oxysterols

Summary

Introduction

Oxysterols are 27-carbon-atom molecules resulting from non-enzymatic or enzymatic oxidation of cholesterol and have been detected in plasma and tissues due to endogenous formation and dietary intake [1,2,3]. High levels of oxysterols, generated by dysfunction in endogenous production or through high dietary intake, can affect cellular metabolism, change membrane composition/property, and promote the onset and progression of major chronic and degenerative diseases such as cancer and atherosclerosis [4, 5]. It is thought that such deleterious effects are due to their ability to trigger cytotoxic, pro-oxidative and pro-inflammatory reactions [6], such as the production of superoxide anions (O-2) and reactive oxygen species (ROS), or through their potential to enhance pro-inflammatory cytokine expression and secretion levels (tumor necrosis factor-α (TNF-α), IL-1β, IL-6, IL-8, monocyte inflammatory protein-1 (MIP-1β), cellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin [7]. EVOO and its bioactive minor components, in particular, oleuropein [14, 15], hydroxytyrosol [16,17,18,19,20,21] and oleocanthal [22, 23], and the entire phenolic fraction [24, 25], have been largely investigated in in vitro models and many findings support their anti-inflammatory and immune-modulatory effects

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