Evidence map›Paper›PMID 22065582›Full record

ArticleThe Journal of biological chemistry2011

Exogenous ceramide-1-phosphate reduces lipopolysaccharide (LPS)-mediated cytokine expression.

Jody L Hankins, Todd E Fox, Brian M Barth, Kellee A Unrath, Mark Kester

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.6field-weighted citation impact, top 17% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 53 citations in OpenAlex.

  1. Role of Ceramide Kinase/C1P in the Regulation of Cell Growth and Survival.International journal of molecular sciences · 2025
    Review
  2. Review
  3. Article
  4. Anti-Obesity Activity ofNutrients · 2024
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Role of Bioactive Sphingolipids in Inflammation and Eye Diseases.Advances in experimental medicine and biology · 2019
    Article
  13. Crosslink between lipids and acute uveitis: a lipidomic analysis.International journal of ophthalmology · 2018
    Article
  14. Review
  15. Translational Aspects of Sphingolipid Metabolism in Renal Disorders.International journal of molecular sciences · 2017
    Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Sphingolipids in spinal cord injury.International journal of physiology, pathophysiology and pharmacology · 2016
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Jody L HankinsDepartment of Pharmacology, Penn State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Todd E Fox
Brian M Barth
Kellee A Unrath
Mark Kester
Pennsylvania State University · USPenn State Milton S. Hershey Medical Center · US

Funding

PKC zeta as a Target for CeramideR01HL076789 · NHLBI · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI KESTER, MARK · 2006 to 2010
$1.8M
NHLBI NIH HHS R01 HL076789NHLBI NIH HHS R01HL076789
6 · The paper itself

Abstract

Toll-like receptor 4 (TLR4) is a component of the innate immune system that recognizes a diverse group of molecular structures, such as lipopolysaccharide (LPS) from Gram-negative bacteria. TLR4 signaling ultimately leads to activation of the transcription factor, nuclear factor κB (NF-κB), and the production of cytokines. Ceramide is a bioactive sphingolipid that has been suggested to regulate TLR4-induced NF-κB signaling, although reports on the role of ceramide in TLR4 activation conflict. We investigated the possibility that ceramide metabolites, such as ceramide-1-phosphate (C-1-P), may explain these discrepancies. We now report that exogenous C-1-P, but not ceramide, reduces NF-κB-mediated gene transcription in HEK 293 cells stably transfected with human TLR4, CD14, and MD-2. We demonstrate that inhibition of NF-κB by exogenous C-1-P is dose-dependent and specific to TLR4 in a reporter assay. We further demonstrate a requirement for both the phosphate moiety and the sphingoid backbone to inhibit LPS-activated NF-κB transcription. Specifically, C-1-P prevents the degradation of IκB, the phosphorylation of the p65 subunit of NF-κB, and LPS-stimulated MAPK activation. The functional consequence of C-1-P inhibition of NF-κB is a reduction in LPS-mediated cytokine release from HEK 293 TLR4-expressing cells and human peripheral blood mononuclear cells. Taken together, these data demonstrate that C-1-P may function as an anti-inflammatory lipid mediator of immune response.

Indexed as

CeramidesCytokinesHEK293 CellsHumansI-kappa B ProteinsLipopolysaccharide ReceptorsLipopolysaccharidesLymphocyte Antigen 96NF-kappa BProteolysisSignal TransductionToll-Like Receptor 4Transcription, Geneticceramide 1-phosphateCeramidesCytokinesI-kappa B Proteinslipopolysaccharide, Escherichia coli O111 B4Lipopolysaccharide ReceptorsLipopolysaccharidesLY96 protein, humanLymphocyte Antigen 96NF-kappa BTLR4 protein, humanToll-Like Receptor 4

Identifiers

PMID22065582
PMCPMC3247944
OpenAlexW2062880614

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.