The alliance of sphingosine-1-phosphate and its receptors in immunity

Laboratory of Immune Cell Signaling, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland 20892, USA.
Nature Reviews Immunology (Impact Factor: 34.99). 10/2008; 8(10):753-63. DOI: 10.1038/nri2400
Source: PubMed


Sphingosine-1-phosphate (S1P) is a biologically active metabolite of plasma-membrane sphingolipids that is essential for immune-cell trafficking. Its concentration is increased in many inflammatory conditions, such as asthma and autoimmunity. Much of the immune function of S1P results from the engagement of a family of G-protein-coupled receptors (S1PR1-S1PR5). Recent findings on the role of S1P in immunosurveillance, the discovery of regulatory mechanisms in S1P-mediated immune-cell trafficking and new advances in understanding the mechanism by which S1P affects immune-cell function indicate that the alliance between S1P and its receptors has a fundamental role in immunity.

Download full-text


Available from: Richard L Proia, Jul 18, 2014
  • Source
    • "Sphingosine-1-phosphate (S1P) is a biologically active metabolite of plasma-membrane sphingolipids, which is essential for immune-cell trafficking (Rivera et al., 2008). It is elevated in many inflammatory diseases, such as asthma and autoimmunity (Rivera et al., 2008). In contrast to its weak effect on degranulation of murine mast cells, S1P potently induces degranulation of human mast cells (LAD2, skin mast cells and hCBMC) (Oskeritzian et al., 2008; Oskeritzian et al., 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Mast cells are crucial effector cells in allergic reactions, where IgE is the best known mechanism to trigger their degranulation and release of a vast array of allergic mediators. However, IgE is not the only component to stimulate these cells to degranulate, while mast cell activation can also result in differential release of mediators. There is a plethora of stimuli, such as IgG, complement components, TLR ligands, neuropeptides, cytokines, chemokines and other inflammatory products, that can directly trigger mast cell degranulation, cause selective release of mediators, and stimulate proliferation, differentiation and/or migration. Moreover, some of these stimuli have a synergic effect on the IgE-mediated mast cell activation. Because of the ability to respond to a large repertoire of stimuli, mast cells may act as a versatile cell in various physiological and pathological conditions. In this review, we discuss current knowledge on non-IgE stimuli for (human) mast cells. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmacology 07/2015; DOI:10.1016/j.ejphar.2015.07.017 · 2.53 Impact Factor
  • Source
    • "In both models, the mechanism for such suppression involved prevention of dendritic or Langerhans cell migration to the lymph nodes (Idzko et al., 2006; Reines et al., 2009) and in the dermatitis model, reduced antigen processing via S1P 2 receptor activation (Japtok et al., 2012). S1P has also been reported to exert anti-inflammatory roles by promoting the switch from the pro-inflammatory M1 to the anti-inflammatory M2 macrophage subtype (reviewed in (Rivera et al., 2008)). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Sphingosine-1phosphate (S1P), platelet activating factor (PAF) and eicosanoids are bioactive lipid mediators abundantly produced by antigen-stimulated mast cells that exert their function mostly through specific cell surface receptors. Although it has long been recognized that some of these bioactive lipids are potent regulators of allergic diseases, their exact contributions to disease pathology have been obscured by the complexity of their mode of action and the regulation of their metabolism. Indeed, the effects of such lipids are usually mediated by multiple receptor subtypes that may differ in their signaling mechanisms and functions. In addition, their actions may be elicited by cell surface receptor-independent mechanisms. Furthermore, these lipids may be converted into metabolites that exhibit different functionalities, adding another layer of complexity to their overall biological responses. In some instances, a second wave of lipid mediator synthesis by both mast cell and non-mast cell sources may occur late during inflammation, bringing about additional roles in the altered environment. New evidence also suggests that bioactive lipids in the local environment can fine-tune mast cell maturation and phenotype, and thus their responsiveness. A better understanding of the subtleties of the spatiotemporal regulation of these lipid mediators, their receptors and functions may aid in the pursuit of pharmacological applications for allergy treatments. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmacology 05/2015; DOI:10.1016/j.ejphar.2015.02.058 · 2.53 Impact Factor
  • Source
    • "S1P is mainly associated to lipoproteins and albumin and its concentrations are around µM in plasma and nM in tissues. S1P can either act as an intracellular second messenger or on the cell surface in an autocrine or paracrine manner by binding to G protein-coupled receptors known as S1P1-5, which generate multiple signals and a fine-tuning of specific responses [8], [11]. S1P receptors are widely expressed in the cardiovascular system, where divergent roles have been reported, including pro- and anti-atherogenic effects [9], [10], cardioprotection [10], [12], [13], and cardiac fibrosis [14]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Given that the bioactive lipid sphingosine 1-phosphate is involved in cardiovascular pathophysiology, and since lipid accumulation and inflammation are hallmarks of calcific aortic stenosis, the role of sphingosine 1-phosphate on the pro-inflammatory/pro-osteogenic pathways in human interstitial cells from aortic and pulmonary valves was investigated. Real-time PCR showed sphingosine 1-phosphate receptor expression in aortic valve interstitial cells. Exposure of cells to sphingosine 1-phosphate induced pro-inflammatory responses characterized by interleukin-6, interleukin-8, and cyclooxygenase-2 up-regulations, as observed by ELISA and Western blot. Strikingly, cell treatment with sphingosine 1-phosphate plus lipopolysaccharide resulted in the synergistic induction of cyclooxygenase-2, and intercellular adhesion molecule 1, as well as the secretion of prostaglandin E2, the soluble form of the intercellular adhesion molecule 1, and the pro-angiogenic factor vascular endothelial growth factor-A. Remarkably, the synergistic effect was significantly higher in aortic valve interstitial cells from stenotic than control valves, and was drastically lower in cells from pulmonary valves, which rarely undergo stenosis. siRNA and pharmacological analysis revealed the involvement of sphingosine 1-phosphate receptors 1/3 and Toll-like receptor-4, and downstream signaling through p38/MAPK, protein kinase C, and NF-κB. As regards pro-osteogenic pathways, sphingosine 1-phosphate induced calcium deposition and the expression of the calcification markers bone morphogenetic protein-2 and alkaline phosphatase, and enhanced the effect of lipopolysaccharide, an effect that was partially blocked by inhibition of sphingosine 1-phosphate receptors 3/2 signaling. In conclusion, the interplay between sphingosine 1-phosphate receptors and Toll-like receptor 4 signaling leads to a cooperative up-regulation of inflammatory, angiogenic, and osteogenic pathways in aortic valve interstitial cells that seems relevant to the pathogenesis of aortic stenosis and may allow the inception of new therapeutic approaches.
    PLoS ONE 10/2014; 9(10):e109081. DOI:10.1371/journal.pone.0109081 · 3.23 Impact Factor
Show more