ArticleNature communications2015
Glucocorticoids limit acute lung inflammation in concert with inflammatory stimuli by induction of SphK1.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04007328 (To Assess the Role of Sphingosine-1-phosphate in the Pathobiology of Pneumonia), which is not on this map. Cited by 86 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.
To Assess the Role of Sphingosine-1-phosphate in the Pathobiology of Pneumonia: Generate a New Strategy for Treatment of Severe Community-acquired Pneumonia
Who cites it
86 citing papers in PubMed, 149 citations in OpenAlex.
- Inverse Correlation Between Plasma Sphingosine-1-Phosphate and Ceramide Concentrations in Septic Patients and Their Utility in Predicting Mortality.Shock (Augusta, Ga.) · 2019Trial
- Tracking COVID-19 Severity and Progression Through Amines and Lipid Mediators.Journal of medical virology · 2026Article
- Article
- SPHK1 drives pyroptosis via ROS-dependent activation of the NLRP3 inflammasome in non-infectious uveitis.Frontiers in immunology · 2026Article
- Epigallocatechin-3-gallate ameliorates lipopolysaccharide-induced inflammation via the 67LR/JAK2/STAT3 signaling pathway.Scientific reports · 2025Article
- JAK/STAT inhibition protects glucocorticoid receptor knockout mice from lethal malaria-induced hypoglycemia and hyperinflammation.EMBO molecular medicine · 2025Article
- Muscle wasting and the response to exercise in lung-injured mice is not primarily driven through the glucocorticoid axis.American journal of physiology. Endocrinology and metabolism · 2025Article
- Glucocorticoid therapy for acute respiratory distress syndrome: Current concepts.Journal of intensive medicine · 2024Review
- Sphingosine kinase 1 is induced by glucocorticoids in adipose derived stem cells and enhances glucocorticoid mediated signaling in adipose expansion.bioRxiv : the preprint server for biology · 2024Article
- Influence of SphK1 on Inflammatory Responses in Lipopolysaccharide-Challenged RAW 264.7 Cells.Cell biochemistry and biophysics · 2024Article
- Glucocorticoid Nanoparticles Show Full Therapeutic Efficacy in a Mouse Model of Acute Lung Injury and Concomitantly Reduce Adverse Effects.International journal of molecular sciences · 2023Article
- Receptor-dependent effects of sphingosine-1-phosphate (S1P) in COVID-19: the black side of the moon.Molecular and cellular biochemistry · 2023Article
- Changes in Cortisol Secretion and Corticosteroid Receptors in COVID-19 and Non COVID-19 Critically Ill Patients with Sepsis/Septic Shock and Scope for Treatment.Biomedicines · 2023Review
- Glucocorticoid activation of anti-inflammatory macrophages protects against insulin resistance.Nature communications · 2023Article
- Protective role of zinc in the pathogenesis of respiratory diseases.European journal of clinical nutrition · 2023Review
- Glucocorticoids and medroxyprogesterone acetate synergize with inflammatory stimuli to selectively upregulate CCL20 transcription.Molecular and cellular endocrinology · 2023Article
- Macrophagic AMPKα1 orchestrates regenerative inflammation induced by glucocorticoids.EMBO reports · 2023Article
- STV-Na attenuates lipopolysaccharide-induced lung injury in mice via the TLR4/NF-kB pathway.Immunity, inflammation and disease · 2023Article
- Different effects of a perioperative single dose of dexamethasone on wound healing in mice with or without sepsis.Frontiers in surgery · 2023Article
- The impact of hepatocyte-specific deletion of hypoxia-inducible factors on the development of polymicrobial sepsis with focus on GR and PPARα function.Frontiers in immunology · 2023Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 10 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute lung injury (ALI) is a severe inflammatory disease for which no specific treatment exists. As glucocorticoids have potent immunosuppressive effects, their application in ALI is currently being tested in clinical trials. However, the benefits of this type of regimen remain unclear. Here we identify a mechanism of glucocorticoid action that challenges the long-standing dogma of cytokine repression by the glucocorticoid receptor. Contrarily, synergistic gene induction of sphingosine kinase 1 (SphK1) by glucocorticoids and pro-inflammatory stimuli via the glucocorticoid receptor in macrophages increases circulating sphingosine 1-phosphate levels, which proves essential for the inhibition of inflammation. Chemical or genetic inhibition of SphK1 abrogates the therapeutic effects of glucocorticoids. Inflammatory p38 MAPK- and mitogen- and stress-activated protein kinase 1 (MSK1)-dependent pathways cooperate with glucocorticoids to upregulate SphK1 expression. Our findings support a critical role for SphK1 induction in the suppression of lung inflammation by glucocorticoids, and therefore provide rationales for effective anti-inflammatory therapies.
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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.