Evidence map›Paper›PMID 25917098›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2015

Prostaglandin E2 Inhibits NLRP3 Inflammasome Activation through EP4 Receptor and Intracellular Cyclic AMP in Human Macrophages.

Milena Sokolowska, Li-Yuan Chen, Yueqin Liu, Asuncion Martinez-Anton, Hai-Yan Qi, Carolea Logun, Sara Alsaaty, Yong Hwan Park, Daniel L Kastner, Jae Jin Chae and 1 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed, 1 pooled it
9.6field-weighted citation impact, top 1% 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

99 citing papers in PubMed, 1 synthesis or guideline pooled it, 166 citations in OpenAlex.

  1. Pooled it
  2. Ticagrelor IncreasesInternational journal of molecular sciences · 2020
    Trial
  3. Article
  4. Regulated Cell Death in Idiopathic Pulmonary Fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. SPMs exert anti-inflammatory and pro-resolving effects through positive allosteric modulation of the prostaglandin EP4 receptor.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Article

39 more citing papers are in PubMed but not listed here.

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

11 authors at 2 institutions in 1 country.

Milena Sokolowska *Critical Care Medicine Department, Clinical Center, NIH, Bethesda, MD, USA.
Li-Yuan Chen *Critical Care Medicine Department, Clinical Center, NIH, Bethesda, MD, USA.
Yueqin LiuCritical Care Medicine Department, Clinical Center, NIH, Bethesda, MD, USA.
Asuncion Martinez-AntonCritical Care Medicine Department, Clinical Center, NIH, Bethesda, MD, USA.
Hai-Yan QiCritical Care Medicine Department, Clinical Center, NIH, Bethesda, MD, USA.
Carolea LogunCritical Care Medicine Department, Clinical Center, NIH, Bethesda, MD, USA.
Sara AlsaatyCritical Care Medicine Department, Clinical Center, NIH, Bethesda, MD, USA.
Yong Hwan ParkInflammatory Disease Section, Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA.
Daniel L KastnerInflammatory Disease Section, Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA.
Jae Jin ChaeInflammatory Disease Section, Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA.
James H ShelhamerCritical Care Medicine Department, Clinical Center, NIH, Bethesda, MD, USA.
National Institutes of Health Clinical Center · USNational Human Genome Research Institute · US

Funding

Genetics, Pathophysiology, and Treatment of Dominant Autoinflammatory DiseasesZIAHG200373 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI KASTNER, DANIEL · 2011 to 2024
$21.0M
STUDY OF CONTROL OF CYTOSOLIC PHOSPHOLIPASE A2 ACTIVITYZ01CL000182 · CLC · CLINICAL CENTER · PI SHELHAMER, JAMES H · 1996 to 2008
$472k
Study Of Control Of Cytosolic Phospholipase A2 ActivityZIACL000182 · CLC · CLINICAL CENTER · PI MASUR, HENRY · 2009 to 2017
$0k
Intramural NIH HHS Z01 CL000182
6 · The paper itself

Abstract

PGE2 is a potent lipid mediator involved in maintaining homeostasis but also promotion of acute inflammation or immune suppression in chronic inflammation and cancer. Nucleotide-binding domain, leucine-rich repeat-containing protein (NLR)P3 inflammasome plays an important role in host defense. Uncontrolled activation of the NLRP3 inflammasome, owing to mutations in the NLRP3 gene, causes cryopyrin-associated periodic syndromes. In this study, we showed that NLRP3 inflammasome activation is inhibited by PGE2 in human primary monocyte-derived macrophages. This effect was mediated through PGE2 receptor subtype 4 (EP4) and an increase in intracellular cAMP, independently of protein kinase A or exchange protein directly activated by cAMP. A specific agonist of EP4 mimicked, whereas its antagonist or EP4 knockdown reversed, PGE2-mediated NLRP3 inhibition. PGE2 caused an increase in intracellular cAMP. Blockade of adenylate cyclase by its inhibitor reversed PGE2-mediated NLRP3 inhibition. Increase of intracellular cAMP by an activator of adenylate cyclase or an analog of cAMP, or a blockade of cAMP degradation by phosphodiesterase inhibitor decreased NLRP3 activation. Protein kinase A or exchange protein directly activated by cAMP agonists did not mimic, and their antagonists did not reverse, PGE2-mediated NLRP3 inhibition. Additionally, constitutive IL-1β secretion from LPS-primed PBMCs of cryopyrin-associated periodic fever syndromes patients was substantially reduced by high doses of PGE2. Moreover, blocking cytosolic phospholipase A2α by its inhibitor or small interfering RNA or inhibiting cyclooxygenase 2, resulting in inhibition of endogenous PGE2 production, caused an increase in NLRP3 inflammasome activation. Our results suggest that PGE2 might play a role in maintaining homeostasis during the resolution phase of inflammation and might serve as an autocrine and paracrine regulator.

Indexed as

Adenylyl Cyclase InhibitorsAdenylyl CyclasesCarrier ProteinsCell LineCryopyrin-Associated Periodic SyndromesCyclic AMPCyclic AMP-Dependent Protein KinasesCyclooxygenase 2Cyclooxygenase 2 InhibitorsDinoprostoneEnzyme ActivationGroup IV Phospholipases A2HumansInflammasomesInflammationInterleukin-1betaAdenylyl Cyclase InhibitorsAdenylyl CyclasesCarrier ProteinsCyclic AMPCyclic AMP-Dependent Protein KinasesCyclooxygenase 2Cyclooxygenase 2 InhibitorsDinoprostoneGroup IV Phospholipases A2IL1B protein, humanInflammasomesInterleukin-1betaLipopolysaccharidesNLR Family, Pyrin Domain-Containing 3 ProteinNLRP3 protein, humanPhosphodiesterase InhibitorsPLA2G4A protein, humanReceptors, Prostaglandin E, EP2 SubtypeReceptors, Prostaglandin E, EP4 SubtypeRNA, Small Interfering

Identifiers

PMID25917098
PMCPMC4433768
OpenAlexW1764212712

What OpenQuestion holds

Textmetadata
LicenceTDM
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.