This work presents for the first time evidence that human neutrophils are highly sensitive to OA and provides novel data in support of a protective role of this monounsaturated acid against the activation of neutrophils during inflammation.

The present work investigates the modulation of grapefruit flavonoid naringenin over liver X receptor alpha (LXRα) and its target genes in THP-1 macrophages, focusing on AMP-activated protein kinase (AMPK) implication. Naringenin induced LXRα at mRNA and protein levels besides influencing the expression of LXRα target genes ABCA1, ABCG1 (ATP-binding cassette A1 and G1), and SREBP1c (sterol response element binding protein 1c) in THP-1 macrophages. The increased LXRα mRNA and protein expression was reverted when AMPK was inhibited by its chemical inhibitor, compound C or by transfection with AMPK α1 and α2 siRNA. Naringenin treatments were also able to promote reverse cholesterol transport in THP-1 cells, which is in line with the increase in the ABCA1 and ABCG1 expression found. Treatments with this flavonoid also inhibited cell migration in THP-1 cells. In conclusion, LXRα and its target genes are up-regulated by naringenin in an AMPK dependent manner in human macrophages. The enhancement in the expression of genes involved in cholesterol efflux may reveal a new mechanism by which this polyphenol can prevent atherosclerosis and foam cell progression.

No abstract

In 2010, the Mediterranean diet was recognized by UNESCO as an Intangible Cultural Heritage of Humanity. Olive oil is the most characteristic food of this diet due to its high nutraceutical value. The positive effects of olive oil have often been attributed to its minor components; however, its oleic acid (OA) content (70–80%) is responsible for its many health properties. OA is an effective biomolecule, although the mechanism by which OA mediates beneficial physiological effects is not fully understood. OA influences cell membrane fluidity, receptors, intracellular signaling pathways, and gene expression. OA may directly regulate both the synthesis and activities of antioxidant enzymes. The anti-inflammatory effect may be related to the inhibition of proinflammatory cytokines and the activation of anti-inflammatory ones. The best-characterized mechanism highlights OA as a natural activator of sirtuin 1 (SIRT1). Oleoylethanolamide (OEA), derived from OA, is an endogenous ligand of the peroxisome proliferator-activated receptor alpha (PPARα) nuclear receptor. OEA regulates dietary fat intake and energy homeostasis and has therefore been suggested to be a potential therapeutic agent for the treatment of obesity. OEA has anti-inflammatory and antioxidant effects. The beneficial effects of olive oil may be related to the actions of OEA. New evidence suggests that oleic acid may influence epigenetic mechanisms, opening a new avenue in the exploration of therapies based on these mechanisms. OA can exert beneficial anti-inflammatory effects by regulating microRNA expression. In this review, we examine the cellular reactions and intracellular processes triggered by OA in T cells, macrophages, and neutrophils in order to better understand the immune modulation exerted by OA.

The present paper describes for the first time that two oxysterols (7-k-chol and 25-OH-chol) enhance the ROS production within a short period of time in human neutrophils, stimulate the translocation of the cytosolic components of NADPH oxidase to the cellular membrane and increase lysozyme secretion. These data suggest that both oxysterols are able to activate pro-inflammatory effects in human neutrophils which contrasts with the role assigned to the oxysterols when they act through LXR at long time of incubation.