Endomorphin-1 prevents lipid accumulation via CD36 down-regulation and modulates cytokines release from human lipid-laden macrophages

CD36 is a scavenger receptor known to play a critical role in the development of atherosclerosis by mediating the uptake of oxidized low-density lipoproteins (oxLDL) by macrophages, thus leading to foam cell formation. It is now generally recognized that the immune system has a pivotal role in the pathogenesis of atherosclerosis, whose progression is determined by ongoing inflammatory reactions. Recently, several studies pointed out that opioid peptides exert anti-inflammatory activities. Therefore the aim of the present study was to evaluate a possible endomorphin-1 (EM-1) immunomodulatory activity on human foam cells. Our results showed that EM-1 reduced Nile Red-stained lipid droplets content, decreased the expression of CD36 receptor and modulated tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) release from lipid-laden macrophages. Furthermore, Naloxone, an opioid receptors antagonist, reverted the anti-atherogenic and anti-inflammatory observed effects of EM-1. These data demonstrated, for the first time, an unprecedented ability of EM-1 to act as a novel modulator for macrophage-to-foam cell transformation, and for inflammatory cytokines profile, suggesting possible novel endomorphin-based anti-atherosclerotic approaches for the prevention and treatment of atherosclerosis.

Research highlights▶ Endomorphin-1 is capable of inhibiting modified lipid accumulation in human foam cell macrophages ▶ Endomorphin-1-induced inhibition of lipid accumulation was mediated by CD36 scavenger receptor down-regulation ▶ Endomorphin-1 may act as novel modulator for macrophage-to-foam cell transformation, exerting both anti-atherogenic and anti-inflammatory activities.