ArticleProstaglandins & other lipid mediators2013
Sphingosine-1-phosphate receptor-2 mediated NFκB activation contributes to tumor necrosis factor-α induced VCAM-1 and ICAM-1 expression in endothelial cells.
Article in Prostaglandins & other lipid mediators, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 58 citations in OpenAlex.
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- ApoA1/HDL and sepsis-associated vascular endothelial injury: a narrative review.Critical care (London, England) · 2025Review
- Fingolimod Modulates the Gene Expression of Proteins Engaged in Inflammation and Amyloid-Beta Metabolism and Improves Exploratory and Anxiety-Like Behavior in Obese Mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Signal Transduction and Gene Regulation in the Endothelium.Cold Spring Harbor perspectives in medicine · 2023Review
- Adipokines in atherosclerosis: unraveling complex roles.Frontiers in cardiovascular medicine · 2023Review
- The Crosstalk between FcεRI and Sphingosine Signaling in Allergic Inflammation.International journal of molecular sciences · 2022Review
- Platelet-Derived S1P and Its Relevance for the Communication with Immune Cells in Multiple Human Diseases.International journal of molecular sciences · 2022Review
- Endothelial Sphingosine-1-Phosphate Receptor 4 Regulates Blood-Brain Barrier Permeability and Promotes a Homeostatic Endothelial Phenotype.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Sphingosine 1-phosphate and its regulatory role in vascular endothelial cells.Histology and histopathology · 2022Review
- Article
- Inhibition of S1P Receptor 2 Attenuates Endothelial Dysfunction and Inhibits Atherogenesis in Apolipoprotein E-Deficient Mice.Journal of atherosclerosis and thrombosis · 2021Article
- Targeting the Sphingosine Kinase/Sphingosine-1-Phosphate Signaling Axis in Drug Discovery for Cancer Therapy.Cancers · 2021Review
- The Role of Sphingolipids in Allergic Disorders.Frontiers in allergy · 2021Review
- Serum Sphingosine-1-Phosphate Is Decreased in Patients With Acute-on-Chronic Liver Failure and Predicts Early Mortality.Hepatology communications · 2020Article
- The S1P-S1PR Axis in Neurological Disorders-Insights into Current and Future Therapeutic Perspectives.Cells · 2020Review
- S1PR2 Inhibition Attenuates Allergic Asthma Possibly by Regulating Autophagy.Frontiers in pharmacology · 2020Article
- Protein phosphatase 2A as a therapeutic target in inflammation and neurodegeneration.Pharmacology & therapeutics · 2019Review
- The Cross-Talk Between Sphingolipids and Insulin-Like Growth Factor Signaling: Significance for Aging and Neurodegeneration.Molecular neurobiology · 2019Review
- CD4 T cell sphingosine 1-phosphate receptor (S1PR)1 and S1PR4 and endothelial S1PR2 regulate afferent lymphatic migration.Science immunology · 2019Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Sphingosine-1-phosphate (S1P) regulates a wide array of biological functions in endothelial cells. We previously showed that S1P receptor subtype 2 (S1P2) is significantly up-regulated in the atherosclerotic endothelium (J. Biol. Chem. 283:30363, 2008). In this study, we investigated the roles of S1P2-mediated signaling in the proinflammatory responses of endothelial cells. Treatment with tumor necrosis factor-α (TNFα), a proinflammatory cytokine, increased the expression of S1P2 receptors in endothelial cells. TNFα treatment also enhanced sphingosine kinase 1 expression and increased S1P production. Pharmacological inhibition or knockdown of S1P2 receptors completely abrogated the TNFα-induced VCAM-1 (vascular cell adhesion molecule 1) and ICAM-1 (intercellular adhesion molecule 1) expression in endothelial cells. In contrast, pharmacological inhibition or knockdown of other S1P receptor subtypes had no effect on the TNFα-stimulated ICAM-1 and VCAM-1 expression. Moreover, ectopic expression of S1P2 receptors increased VCAM-1 and ICAM-1 expression in endothelial cells in response to S1P stimulation. Mechanistically, we show that antagonizing S1P2 signaling markedly inhibited the TNFα-stimulated NFκB activation. Utilizing the NFκB reporter luciferase assay, the S1P/S1P2 signaling was shown to stimulate NFκB activation. Moreover, the S1P/S1P2-stimulated VCAM-1/ICAM-1 expression was completely abolished by the pharmacological inhibitor of NFκB. Collectively, our data suggest that TNFα treatment activates autocrine S1P/S1P2 signaling, which subsequently activates NFκB and leads to the proinflammatory responses in endothelial cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.