Endomorphin-1 Inhibits the Activation and the Development of a Hyporesponsive-like Phenotype in Lipopolysaccharide-Stimulated THP-1 Monocytes

Abstract

Endomorphin-l (EM-I) is an endogenous opioid peptide selectively binding to J1 opioid receptors (MORs). Besides its analgesic effects on the central nervous system (CNS), it has been recently reported that EM-l can cross the blood-brain barrier (BBB) and diffuse into the blood, behaving as an analgesic/ anti-inflammatory molecule on peripheral tissues, thus leading to the hypothesis that it could represent a soluble modulator of immune cell functions. Interestingly, nothing is known about its possible effects on monocytes, the main circulating cell-type involved in those systemic responses, such as fever and septic states, involving the release of high amounts of pyrogenic inflammatory factors. The aim of this work is to evaluate possible EM-leffects on Iipopolisaccharide (LPS)-stimulated THP-I monocytes in terms of the production of inflammatory mediators and the instauration of a hyporesponsive-Iike phenotype which is a main feature of systemic inflammatory responses, and on the development of peripheral monocytes to DC. Our data demonstrate for the first time that EM-I is able to inhibit both LPS-stimulated monocyte activation, in terms of arachidonic acid, PGE 2 , ROI and NO z production and instauration of a hypo responsive phenotype without any macroscopic effect on DC development. These data support the hypothesis that EM-I could be involved in modulating monocyte functions during systemic inflammatory reactions, also providing new evidence for its eventual clinical application in endotoxic states.Endomorphin-I (EM-I) is an ammidated tetrapeptide discovered by Zadina et aL in human tissues mostly belonging to the nervous and the immune system (1-2). To date, EM-l is thought to be a powerful endogenous analgesic molecule, 'as its presence in the nervous system has been traced in those areas involved in pain perception (nociception) and in the spinal antinociceptive descending pathways (2-3). Notably, it has also been recently demonstrated that EM-l can cross the blood-brain barrier (BBB), thus entering the blood flow and possibly reaching areas of the body far

Activation of GPR55 Receptors Exacerbates oxLDL-Induced Lipid Accumulation and Inflammatory Responses, while Reducing Cholesterol Efflux from Human Macrophages

“…Cells were cultured at 37°C in a humidified 5% CO 2 atmosphere. THP-1 monocytes were differentiated into macrophages in the presence of 100 nM phorbol 12-myristate 13-acetate (PMA, Sigma Aldrich, Italy) for 72h, as reported [ 26 , 27 , 28 ]. All cell pre-treatments and treatments were performed in absence of serum.…”

Impact of IL-32 on Histamine Release by Human Derived Umbilical Cord Blood Mast Cells

“…The response of mast cells to non-IgE-mediated stimulation is critically dependent on the population of mast cells examined. IL-32 has been reported to activate inflammatory cells (46)(47)(48)(49)(50). Responsiveness to IL-32 was monitored measuring histamine release on HDC mRNA expression.…”

Mast Cells and Arachidonic Acid Cascade in Inflammation

“…Prostaglandins and leukotrienes are proinflammatory mediators resulting from metabolic degradation of the arachidonic acid originating from membrane phospholipids. Mast cells release substances such as histamine, leukotrienes B4, C4 and 04, 5-hydroxyeicosatetraenoic acid, Prostaglandin 02 (PGD2), Platelet Activating Factor (PAF), heparin and contain tryptase and chymase (9)(10)(11)(12)(13). The most important products of enzyme cyclooxygenation of arachidonic acid are prostaglandins D2, E2, F2a, tromboxane A2 and prostacyclin (14)(15).…”