ArticleThe Journal of biological chemistry2013
Sphingosine kinases are not required for inflammatory responses in macrophages.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 46 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
46 citing papers in PubMed, 70 citations in OpenAlex.
- Sphingosine-1-Phosphate Regulation to Alleviate Sickle Cell Disease Severity: A Promising Therapeutic Approach.Saudi medical journal · 2026Review
- Sphingosine-1-Phosphate Metabolic Pathway in Cancer: Implications for Therapeutic Targets.International journal of molecular sciences · 2025Review
- An intestinal sphingolipid confers intergenerational neuroprotection.Nature cell biology · 2023Article
- Sphingosine Kinases at the Intersection of Pro-Inflammatory LPS and Anti-Inflammatory Endocannabinoid Signaling in BV2 Mouse Microglia Cells.International journal of molecular sciences · 2023Article
- Myeloid-specific fatty acid transport protein 4 deficiency induces a sex-dimorphic susceptibility for nonalcoholic steatohepatitis in mice fed a high-fat, high-cholesterol diet.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- Article
- The Impact of Sphingosine Kinases on Inflammation-Induced Cytokine Release and Vascular Endothelial Barrier Integrity.International journal of molecular sciences · 2022Article
- Ablation of Sphingosine Kinase 1 Protects Cornea from Neovascularization in a Mouse Corneal Injury Model.Cells · 2022Article
- Sphingosine-1-Phosphate (S1P) Lyase Inhibition Aggravates Atherosclerosis and Induces Plaque Rupture inInternational journal of molecular sciences · 2022Article
- Review
- Sphingolipid metabolism governs Purkinje cell patterned degeneration inProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Cellular stress promotes NOD1/2-dependent inflammation via the endogenous metabolite sphingosine-1-phosphate.The EMBO journal · 2021Article
- Sphingolipids in Lung Pathology in the Coronavirus Disease Era: A Review of Sphingolipid Involvement in the Pathogenesis of Lung Damage.Frontiers in physiology · 2021Review
- Sphingosine Kinases are Involved in Macrophage NLRP3 Inflammasome Transcriptional Induction.International journal of molecular sciences · 2020Article
- SPHK2-Generated S1P in CD11bCell reports · 2020Article
- Reduction of Sphingosine Kinase 1 Phosphorylation and Activity inFrontiers in cell and developmental biology · 2020Article
- Sphingosine kinase-2 prevents macrophage cholesterol accumulation and atherosclerosis by stimulating autophagic lipid degradation.Scientific reports · 2019Article
- Sphingosine 1-phosphate: Lipid signaling in pathology and therapy.Science (New York, N.Y.) · 2019Review
- Regulation of ABCA1-mediated cholesterol efflux by sphingosine-1-phosphate signaling in macrophages.Journal of lipid research · 2019Article
- Sphingosine-1-Phosphate and Macrophage Biology-How the Sphinx Tames the Big Eater.Frontiers in immunology · 2019Review
Corrections and comments
- Erratum issuedSphingosine kinases are not required for inflammatory responses in macrophages.2016 · Lee, Hyeuk Jong [corrected to Lee, Hyuek Jong]
Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Sphingosine kinases (Sphks), which catalyze the formation of sphingosine 1-phosphate (S1P) from sphingosine, have been implicated as essential intracellular messengers in inflammatory responses. Specifically, intracellular Sphk1-derived S1P was reported to be required for NFκB induction during inflammatory cytokine action. To examine the role of intracellular S1P in the inflammatory response of innate immune cells, we derived murine macrophages that lack both Sphk1 and Sphk2 (MΦ Sphk dKO). Compared with WT counterparts, MΦ Sphk dKO cells showed marked suppression of intracellular S1P levels whereas sphingosine and ceramide levels were strongly up-regulated. Cellular proliferation and apoptosis were similar in MΦ Sphk dKO cells compared with WT counterparts. Treatment of WT and MΦ Sphk dKO with inflammatory mediators TNFα or Escherichia coli LPS resulted in similar NFκB activation and cytokine expression. Furthermore, LPS-induced inflammatory responses, mortality, and thioglycolate-induced macrophage recruitment to the peritoneum were indistinguishable between MΦ Sphk dKO and littermate control mice. Interestingly, autophagic markers were constitutively induced in bone marrow-derived macrophages from Sphk dKO mice. Treatment with exogenous sphingosine further enhanced intracellular sphingolipid levels and autophagosomes. Inhibition of autophagy resulted in caspase-dependent cell death. Together, these data suggest that attenuation of Sphk activity, particularly Sphk2, leads to increased intracellular sphingolipids and autophagy in macrophages.
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.