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| Subject | Predicate | Object |
|---|---|---|
| http://purl.uniprot.org/citations/30188757 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30188757 | http://www.w3.org/2000/01/rdf-schema#comment | "Sphingosine-1-phosphate (S1P) is involved in the regulation of important cellular processes, including immune-cell trafficking and proliferation. Altered S1P signaling is strongly associated with inflammation, cancer progression, and atherosclerosis; however, the mechanisms underlying its pathophysiologic effects are only partially understood. This study evaluated the effects of S1P in vitro and in vivo on the biosynthesis of leukotrienes (LTs), which form a class of lipid mediators involved in the pathogenesis of inflammatory diseases. Here, we report for the first time that S1P potently suppresses LT biosynthesis in Ca2+-ionophore-stimulated intact human neutrophils. S1P treatment resulted in intracellular Ca2+ mobilization, perinuclear translocation, and finally irreversible suicide inactivation of the LT biosynthesis key enzyme 5-lipoxygenase (5-LO). Agonist studies and S1P receptor mRNA expression analysis provided evidence for a S1P receptor 4-mediated effect, which was confirmed by a functional knockout of S1P4 in HL60 cells. Systemic administration of S1P in wild-type mice decreased both macrophage and neutrophil migration in the lungs in response to LPS and significantly attenuated 5-LO product formation, whereas these effects were abrogated in 5-LO or S1P4 knockout mice. In summary, targeting the 5-LO pathway is an important mechanism to explain S1P-mediated pathophysiologic effects. Furthermore, agonism at S1P4 represents a novel effective strategy in pharmacotherapy of inflammation.-Fettel, J., Kühn, B., Guillen, N. A., Sürün, D., Peters, M., Bauer, R., Angioni, C., Geisslinger, G., Schnütgen, F., Meyer zu Heringdorf, D., Werz, O., Meybohm, P., Zacharowski, K., Steinhilber, D., Roos, J., Maier, T. J. Sphingosine-1-phosphate (S1P) induces potent anti-inflammatory effects in vitro and in vivo by S1P receptor 4-mediated suppression of 5-lipoxygenase activity."xsd:string |
| http://purl.uniprot.org/citations/30188757 | http://purl.org/dc/terms/identifier | "doi:10.1096/fj.201800221r"xsd:string |
| http://purl.uniprot.org/citations/30188757 | http://purl.uniprot.org/core/author | "Bauer R."xsd:string |
| http://purl.uniprot.org/citations/30188757 | http://purl.uniprot.org/core/author | "Roos J."xsd:string |
| http://purl.uniprot.org/citations/30188757 | http://purl.uniprot.org/core/author | "Peters M."xsd:string |
| http://purl.uniprot.org/citations/30188757 | http://purl.uniprot.org/core/author | "Geisslinger G."xsd:string |
| http://purl.uniprot.org/citations/30188757 | http://purl.uniprot.org/core/author | "Kuhn B."xsd:string |
| http://purl.uniprot.org/citations/30188757 | http://purl.uniprot.org/core/author | "Angioni C."xsd:string |
| http://purl.uniprot.org/citations/30188757 | http://purl.uniprot.org/core/author | "Werz O."xsd:string |
| http://purl.uniprot.org/citations/30188757 | http://purl.uniprot.org/core/author | "Steinhilber D."xsd:string |
| http://purl.uniprot.org/citations/30188757 | http://purl.uniprot.org/core/author | "Schnutgen F."xsd:string |
| http://purl.uniprot.org/citations/30188757 | http://purl.uniprot.org/core/author | "Meybohm P."xsd:string |
| http://purl.uniprot.org/citations/30188757 | http://purl.uniprot.org/core/author | "Zacharowski K."xsd:string |
| http://purl.uniprot.org/citations/30188757 | http://purl.uniprot.org/core/author | "Meyer Zu Heringdorf D."xsd:string |
| http://purl.uniprot.org/citations/30188757 | http://purl.uniprot.org/core/author | "Maier T.J."xsd:string |
| http://purl.uniprot.org/citations/30188757 | http://purl.uniprot.org/core/author | "Surun D."xsd:string |
| http://purl.uniprot.org/citations/30188757 | http://purl.uniprot.org/core/author | "Guillen N.A."xsd:string |
| http://purl.uniprot.org/citations/30188757 | http://purl.uniprot.org/core/author | "Fettel J."xsd:string |
| http://purl.uniprot.org/citations/30188757 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |
| http://purl.uniprot.org/citations/30188757 | http://purl.uniprot.org/core/name | "FASEB J"xsd:string |
| http://purl.uniprot.org/citations/30188757 | http://purl.uniprot.org/core/pages | "1711-1726"xsd:string |
| http://purl.uniprot.org/citations/30188757 | http://purl.uniprot.org/core/title | "Sphingosine-1-phosphate (S1P) induces potent anti-inflammatory effects in vitro and in vivo by S1P receptor 4-mediated suppression of 5-lipoxygenase activity."xsd:string |
| http://purl.uniprot.org/citations/30188757 | http://purl.uniprot.org/core/volume | "33"xsd:string |
| http://purl.uniprot.org/citations/30188757 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/30188757 |