Beyond Immune Cell Migration: The Emerging Role of the Sphingosine-1-phosphate Receptor S1PR4 as a Modulator of Innate Immune Cell Activation

Olesch, Catherine; Ringel, Christian; Brüne, Bernhard; Weigert, Andreas

doi:10.1155/2017/6059203

Cited by 57 publications

(48 citation statements)

References 104 publications

(148 reference statements)

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“…S1PR4 is expressed predominantly in immune cells such as T cells and dendritic cells and is thought to modulate IL-17 production and IL-27 production. 33 As shown in Fig. 4D, median expression of S1PR4 in moderate/severe IBD was also significantly upregulated relative to controls and IBD patients in remission.…”

Section: Resultsmentioning

confidence: 67%

Sphingosine-1-Phosphate Signaling and Metabolism Gene Signature in Pediatric Inflammatory Bowel Disease: A Matched-case Control Pilot Study

Suh

Degagné

Gleghorn

et al. 2018

Inflammatory Bowel Diseases

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Goal The aim of this study was to investigate gene expression levels of proteins involved in sphingosine-1-phosphate (S1P) metabolism and signaling in a pediatric inflammatory bowel disease (IBD) patient population. Background IBD is a debilitating disease affecting 0.4% of the US population. The incidence of IBD in childhood is rising. Identifying effective targeted therapies that can be used safely in young patients and developing tools for selecting specific candidates for targeted therapies are important goals. Clinical IBD trials now underway target S1PR1, a receptor for the pro-inflammatory sphingolipid S1P. However, circulating and tissue sphingolipid levels and S1P-related gene expression have not been characterized in pediatric IBD. Methods Pediatric IBD patients and controls were recruited in a four-site study. Patients received a clinical score using PUCAI or PCDAI evaluation. Colon biopsies were collected during endoscopy. Gene expression was measured by qRT-PCR. Plasma and gut tissue sphingolipids were measured by LC-MS/MS. Results Genes of S1P synthesis (SPHK1, SPHK2), degradation (SGPL1), and signaling (S1PR1, S1PR2, and S1PR4) were significantly upregulated in colon biopsies of IBD patients with moderate/severe symptoms compared with controls or patients in remission. Tissue ceramide, dihydroceramide, and ceramide-1-phosphate (C1P) levels were significantly elevated in IBD patients compared with controls. Conclusions A signature of elevated S1P-related gene expression in colon tissues of pediatric IBD patients correlates with active disease and normalizes in remission. Biopsied gut tissue from symptomatic IBD patients contains high levels of pro-apoptotic and pro-inflammatory sphingolipids. A combined analysis of gut tissue sphingolipid profiles with this S1P-related gene signature may be useful for monitoring response to conventional therapy.

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Section: Resultsmentioning

confidence: 67%

Sphingosine-1-Phosphate Signaling and Metabolism Gene Signature in Pediatric Inflammatory Bowel Disease: A Matched-case Control Pilot Study

Suh

Degagné

Gleghorn

et al. 2018

Inflammatory Bowel Diseases

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“…1.6 | S1PR4 S1PR4, although less studied than other receptors, is abundant on immune cells (Olesch, Ringel, Brüne, & Weigert, 2017). S1PR4 signals through G-alpha subunits G i and G 12/13 (Gräler et al, 2003).…”

Section: S1pr2mentioning

confidence: 99%

Sphingosine-1-phosphate receptors and innate immunity

Bryan

Poeta

2018

Cellular Microbiology

122

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Sphingosine-1-phosphate (S1P) is a signalling lipid that regulates many cellular processes in mammals. One well-studied role of S1P signalling is to modulate T-cell trafficking, which has a major impact on adaptive immunity. Compounds that target S1P signalling pathways are of interest for immune system modulation. Recent studies suggest that S1P signalling regulates many more cell types and processes than previously appreciated. This review will summarise current understanding of S1P signalling, focusing on recent novel findings in the roles of S1P receptors in innate immunity.

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“…S1PR1, S1PR2, and S1PR3 are extensively distributed in various tissues, while S1PR4 and S1PR5 are restricted to the immune system and nervous system, respectively (Rosenfeldt, Hobson, Milstien, & Spiegel, ). We theorize that there may be an immune component involved in the reproductive system which is mediated by S1PR4, although we do not have other evidence for this, the fact that the receptor is present we may be interested in further pursuing this in the future (Olesch, Ringel, Brüne, & Weigert, ). The maternal‐fetal immune response is vital for development, this although partially characterized still is relatively not well understood.…”

Section: Discussionmentioning

confidence: 99%

Sphingosine‐1‐phosphate (S1P) analog phytosphingosine‐1‐phosphate (P1P) improves the in vitro maturation efficiency of porcine oocytes via regulation of oxidative stress and apoptosis

Park

Wang

Yoo

et al. 2019

Molecular Reproduction Devel

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Phytosphingosine‐1‐phosphate (P1P) is a signaling sphingolipid that regulates various physiological activities. However, little is known about the effect of P1P in the context of reproduction. Thus, we aimed to investigate the influence of P1P on oocyte maturation during porcine in vitro maturation (IVM). Here, we report the expression of S1PR1–3 among P1P receptors (S1PR1–4) in cumulus cells and oocytes. When P1P was administered at concentrations of 10, 50, 100, and 1,000 nM during IVM, the metaphase II rate was significantly increased in the 1,000 nM (1 μM) P1P treatment group. Maturation rate improvement by P1P supplementation was observed only in the presence of epidermal growth factor (EGF). Oocytes under the influence of P1P showed decreased intracellular reactive oxygen species levels but no significant differences in glutathione levels. In our molecular studies, P1P treatment upregulated gene expression involved in cumulus expansion (Has2 and EGF), antioxidant enzymes (SOD3 and Cat), and developmental competence (Oct4) while activating extracellular signal‐regulated kinase1/2 and Akt signaling. P1P treatment also influenced oocyte survival by shifting the ratio of Bcl‐2 to Bax while inactivating JNK signaling. We further demonstrated that oocytes matured with P1P displayed significantly higher developmental competence (cleavage and blastocyst [BL] formation rate) and greater BL quality (total cell number and the ratio of apoptotic cells) when activated via parthenogenetic activation (PA) and in vitro fertilization. Despite the low levels of endogenous P1P found in animals, exogenous P1P influenced animal reproduction, as shown by increased porcine oocyte maturation as well as preimplantation embryo development. This study and its findings are potentially relevant for both human and animal‐assisted reproduction.

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Beyond Immune Cell Migration: The Emerging Role of the Sphingosine-1-phosphate Receptor S1PR4 as a Modulator of Innate Immune Cell Activation

Cited by 57 publications

References 104 publications

Sphingosine-1-Phosphate Signaling and Metabolism Gene Signature in Pediatric Inflammatory Bowel Disease: A Matched-case Control Pilot Study

Sphingosine-1-Phosphate Signaling and Metabolism Gene Signature in Pediatric Inflammatory Bowel Disease: A Matched-case Control Pilot Study

Sphingosine-1-phosphate receptors and innate immunity

Sphingosine‐1‐phosphate (S1P) analog phytosphingosine‐1‐phosphate (P1P) improves the in vitro maturation efficiency of porcine oocytes via regulation of oxidative stress and apoptosis

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