Observational studyEBioMedicine2020
S1P lyase inhibition protects against sepsis by promoting disease tolerance via the S1P/S1PR3 axis.
Observational study in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- Mechanistic insights and therapeutic potential of sphingosine‑1‑phosphate in the development of pulmonary fibrosis (Review).Molecular medicine reports · 2026Review
- Maternal Low-Fat and High-Fat Diet Decreases Survival and Alters Cytokine Signaling in Neonatal Mice With Staphylococcus epidermidis Sepsis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Blood-borne sphingosine 1-phosphate maintains vascular resistance, blood pressure, and cardiac function in mice.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Survival of the Littlest: Navigating Sepsis Diagnosis beyond Inflammation in Preterm Neonates.Journal of proteome research · 2025Article
- SPHK1/S1PR1/PPAR-α axis restores TJs between uroepithelium providing new ideas for IC/BPS treatment.Life science alliance · 2025Article
- Cystathionine γ-lyase-derived HActa pharmacologica Sinica · 2024Article
- Spinster homolog 2/S1P signaling ameliorates macrophage inflammatory response to bacterial infections by balancing PGECell communication and signaling : CCS · 2024Article
- Deletion of Sphingosine Kinase 2 Attenuates Acute Kidney Injury in Mice with Hemolytic-Uremic Syndrome.International journal of molecular sciences · 2024Article
- S1PR3 inhibition protects against LPS-induced ARDS by inhibiting NF-κB and improving mitochondrial oxidative phosphorylation.Journal of translational medicine · 2024Article
- S1PR3 suppresses the inflammatory response and extracellular matrix degradation in human nucleus pulposus cells.Experimental and therapeutic medicine · 2024Article
- Article
- Sphingolipid-Based Synergistic Interactions to Enhance Chemosensitivity in Lung Cancer Cells.Cells · 2023Article
- The role of sphingosine-1-phosphate in autophagy and related disorders.Cell death discovery · 2023Review
- Neutrophilia in severe asthma is reduced in Ormdl3 overexpressing mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- S1P lyase inhibition prevents lung injury following high pressure-controlled mechanical ventilation in aging mice.Experimental gerontology · 2023Article
- Article
- Sepsis-Associated Encephalopathy and Blood-Brain Barrier Dysfunction.Inflammation · 2021Review
- Sphingosine-1 Phosphate Lyase Regulates Sensitivity of Pancreatic Beta-Cells to Lipotoxicity.International journal of molecular sciences · 2021Article
- Nuclear Sphingosine-1-phosphate Lyase Generated ∆2-hexadecenal is A Regulator of HDAC Activity and Chromatin Remodeling in Lung Epithelial Cells.Cell biochemistry and biophysics · 2021Article
- Lysolipids in Vascular Development, Biology, and Disease.Arteriosclerosis, thrombosis, and vascular biology · 2021Review
Corrections and comments
- Commented on by
Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundOne-third of all deaths in hospitals are caused by sepsis. Despite its demonstrated prevalence and high case fatality rate, antibiotics remain the only target-oriented treatment option currently available. Starting from results showing that low-dose anthracyclines protect against sepsis in mice, we sought to find new causative treatment options to improve sepsis outcomes.
methodsSepsis was induced in mice, and different treatment options were evaluated regarding cytokine and biomarker expression, lung epithelial cell permeability, autophagy induction, and survival benefit. Results were validated in cell culture experiments and correlated with patient samples.
findingsEffective low-dose epirubicin treatment resulted in substantial downregulation of the sphingosine 1-phosphate (S1P) degrading enzyme S1P lyase (SPL). Consequent accumulation and secretion of S1P in lung parenchyma cells stimulated the S1P-receptor type 3 (S1PR3) and mitogen-activated protein kinases p38 and ERK, reducing tissue damage via increased disease tolerance. The protective effects of SPL inhibition were absent in S1PR3 deficient mice. Sepsis patients showed increased expression of SPL, stable expression of S1PR3, and increased levels of mucin-1 and surfactant protein D as indicators of lung damage.
interpretationOur work highlights a tissue-protective effect of SPL inhibition in sepsis due to activation of the S1P/S1PR3 axis and implies that SPL inhibitors and S1PR3 agonists might be potential therapeutics to protect against sepsis by increasing disease tolerance against infections.
fundingThis study was supported by the Center for Sepsis Control and Care (CSCC), the German Research Foundation (DFG), RTG 1715 (to M. H. G. and I. R.) and the National Institutes of Health, Grant R01GM043880 (to S. S.).
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.