ArticleCritical care medicine2014
FTY720 (s)-phosphonate preserves sphingosine 1-phosphate receptor 1 expression and exhibits superior barrier protection to FTY720 in acute lung injury.
Article in Critical care medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
29 citing papers in PubMed, 48 citations in OpenAlex.
- Extracellular Vesicles as Drivers of Lung Endothelial Dysfunction in ARDS: Mechanisms and Therapeutic Opportunities.Comprehensive Physiology · 2026Review
- Fingolimod Suppresses NLRP3 Inflammasome Activation and Alleviates Oxidative Stress in Traumatic Brain Injury-Induced Acute Lung Injury.Journal of inflammation research · 2025Article
- Rationale for Use of Sphingosine-1-Phosphate Receptor Modulators in COVID-19 Patients: Overview of Scientific Evidence.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2023Review
- The role of G protein-coupled receptor in neutrophil dysfunction during sepsis-induced acute respiratory distress syndrome.Frontiers in immunology · 2023Review
- Alveolus analysis: a web browser-based tool to analyze lung intravital microscopy.BMC pulmonary medicine · 2022Article
- Fingolimod does not prevent syndecan-4 shedding from the endothelial glycocalyx in a cultured human umbilical vein endothelial cell model of vascular injury.Intensive care medicine experimental · 2022Article
- Molecular Pharmacology and Novel Potential Therapeutic Applications of Fingolimod.Frontiers in pharmacology · 2022Review
- MRSA-induced endothelial permeability and acute lung injury are attenuated by FTY720 S-phosphonate.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Barrier maintenance by S1P during inflammation and sepsis.Tissue barriers · 2021Review
- Fingolimod attenuates renal ischemia/reperfusion-induced acute lung injury by inhibiting inflammation and apoptosis and modulating S1P metabolism.The Journal of international medical research · 2021Article
- Lysophospholipids in Lung Inflammatory Diseases.Advances in experimental medicine and biology · 2021Article
- Rationale for the use of sphingosine analogues in COVID-19 patients.Clinical medicine (London, England) · 2021Review
- Lipid Mediators Regulate Pulmonary Fibrosis: Potential Mechanisms and Signaling Pathways.International journal of molecular sciences · 2020Review
- Merits and culprits of immunotherapies for neurological diseases in times of COVID-19.EBioMedicine · 2020Review
- Article
- Sphingosine 1-Phosphate Receptor 1 Signaling Maintains Endothelial Cell Barrier Function and Protects Against Immune Complex-Induced Vascular Injury.Arthritis & rheumatology (Hoboken, N.J.) · 2018Article
- Linarin prevents LPS‑induced acute lung injury by suppressing oxidative stress and inflammation via inhibition of TXNIP/NLRP3 and NF‑κB pathways.International journal of molecular medicine · 2018Article
- Sphingolipids Signaling in Lamellipodia Formation and Enhancement of Endothelial Barrier Function.Current topics in membranes · 2018Article
- Sphingosine-1-Phosphate Treatment Can Ameliorate Microvascular Leakage Caused by Combined Alcohol Intoxication and Hemorrhagic Shock.Scientific reports · 2017Article
- The Consequences of Overlapping G-Quadruplexes and i-Motifs in the Platelet-Derived Growth Factor Receptor β Core Promoter Nuclease Hypersensitive Element Can Explain the Unexpected Effects of Mutations and Provide Opportunities for Selective Targeting of Both Structures by Small Molecules To Downregulate Gene Expression.Journal of the American Chemical Society · 2017Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveEffective therapies are needed to reverse the increased vascular permeability that characterizes acute inflammatory diseases such as acute lung injury. FTY720 is a pharmaceutical analog of the potent barrier-enhancing phospholipid, sphingosine 1-phosphate. Because both FTY720 and sphingosine 1-phosphate have properties that may limit their usefulness in patients with acute lung injury, alternative compounds are needed for therapeutic use. The objective of this study is to characterize the effects of FTY720 (S)-phosphonate, a novel analog of FTY720-phosphate, on variables of pulmonary vascular permeability in vitro and alveolar-capillary permeability in vivo.
settingUniversity-affiliated research institute. SUBJECTS: Cultured human pulmonary endothelial cells; C57BL/6 mice.
interventionsEndothelial cells were stimulated with sphingosine 1-phosphate receptor 1 agonists to determine effects on sphingosine 1-phosphate receptor 1 expression. Acute lung injury was induced in C57BL/6 mice with bleomycin to assess effects of sphingosine 1-phosphate receptor 1 agonists. MEASUREMENTS AND MAIN
resultsFTY720 (S)-phosphonate potently increases human pulmonary endothelial cell barrier function in vitro as measured by transendothelial electrical resistance. Reduction of sphingosine 1-phosphate receptor 1 with small interference RNA significantly attenuates this transendothelial electrical resistance elevation. FTY720 (S)-phosphonate maintains endothelial sphingosine 1-phosphate receptor 1 protein expression in contrast to greater than 50% reduction after incubation with sphingosine 1-phosphate, FTY720, or other sphingosine 1-phosphate receptor 1 agonists. FTY720 (S)-phosphonate does not induce β-arrestin recruitment, sphingosine 1-phosphate receptor 1 ubiquitination, and proteosomal degradation that occur after other agonists. Intraperitoneal administration of FTY720 (S)-phosphonate every other day for 1 week in normal or bleomycin-injured mice maintains significantly higher lung sphingosine 1-phosphate receptor 1 expression compared with FTY720. FTY720 fails to protect against bleomycin-induced acute lung injury in mice, while FTY720 (S)-phosphonate significantly decreases lung leak and inflammation.
conclusionFTY720 (S)-phosphonate is a promising barrier-promoting agent that effectively maintains sphingosine 1-phosphate receptor 1 levels and improves outcomes in the bleomycin model of acute lung injury.
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