ArticleThe Journal of clinical investigation2002
The prostaglandin receptor EP4 suppresses colitis, mucosal damage and CD4 cell activation in the gut.
Article in The Journal of clinical investigation, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00296556 (A Randomized, Placebo-Controlled Trial of ONO-4819CD for Treatment of Mild to Moderate Ulcerative Colitis.), which is not on this map. Cited by 192 papers, 2 of them syntheses that pooled 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.
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.
A Randomized, Placebo-Controlled Trial of ONO-4819CD for Treatment of Mild to Moderate Ulcerative Colitis.
Who cites it
192 citing papers in PubMed, 2 syntheses or guidelines pooled it, 440 citations in OpenAlex.
- Association between PTGER4 polymorphisms and inflammatory bowel disease risk in Caucasian: A meta-analysis.Medicine · 2020Pooled it
- Quality of methods reporting in animal models of colitis.Inflammatory bowel diseases · 2015Pooled it
- Gut microbiota in chronic inflammation: the interplay with lipid mediators.Gut microbes · 2026Review
- The update of prostaglandin E2 receptor subtype 4 (EP4) in inflammatory diseases.Genes & diseases · 2026Review
- First-in-human phase I study of DT-9081, a selective EP4 receptor antagonist, in advanced solid tumors.Investigational new drugs · 2026Article
- Selective EP4 Receptor Antagonism for Osteoarthritis Pain: Emerging Evidence and Future Directions for KF-0210.Pain and therapy · 2026Review
- What we know about prostaglandin pathway dysfunction in chronic enteropathies: From endoscopy to molecular diagnosis.Journal of translational internal medicine · 2026Article
- Cellulose Nanocrystal-Based Sulfatase-Responsive Hydrogel for Sustained Celecoxib Release in Ulcerative Colitis Therapy.Biomaterials research · 2026Article
- Eosinophil-derived COX-2 protects against experimental colitis through the PGEbioRxiv : the preprint server for biology · 2025Article
- Butyrate, IL-4, and EP4 Receptors: A Triad of Colorectal Homeostasis, Protecting Against Onset of Cancer and IBD?BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Severe anemia in preterm infants associated with increased bacterial virulence potential and metabolic disequilibrium.Pediatric research · 2025Article
- Exploring Oxylipins in Host-Microbe Interactions and Their Impact on Infection and Immunity.Current issues in molecular biology · 2025Review
- The Multifaceted Impact of Bioactive Lipids on Gut Health and Disease.International journal of molecular sciences · 2024Review
- PTGER4 signaling regulates class IIa HDAC function and SPINK4 mRNA levels in rectal epithelial cells.Cell communication and signaling : CCS · 2024Article
- 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 · 2024Article
- Article
- PGENature · 2024Article
- Bacterial indole-3-lactic acid affects epithelium-macrophage crosstalk to regulate intestinal homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- G protein-coupled receptors: A target for microbial metabolites and a mechanistic link to microbiome-immune-brain interactions.Brain, behavior, & immunity - health · 2023Review
- The Role of Lipids in the Regulation of Immune Responses.Nutrients · 2023Review
132 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
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We used mice deficient in each of the eight types and subtypes of prostanoid receptors and examined the roles of prostanoids in dextran sodium sulfate-induced (DSS-induced) colitis. Among the prostanoid receptor-deficient mice, only EP4-deficient mice and not mice deficient in either DP, EP1, EP2, EP3, FP, IP, or TP developed severe colitis with 3% DSS treatment, which induced only marginal colitis in wild-type mice. This phenotype was mimicked in wild-type mice by administration of an EP4-selective antagonist (AE3-208). The EP4 deficiency impaired mucosal barrier function and induced epithelial loss, crypt damage, and aggregation of neutrophils and lymphocytes in the colon. Conversely, administration of an EP4-selective agonist (AE1-734) to wild-type mice ameliorated severe colitis normally induced with 7% DSS, while that of AE3-208 suppressed recovery from colitis and induced significant proliferation of CD4+ T cells. In vitro AE3-208 enhanced and AE1-734 suppressed the proliferation and Th1 cytokine production of lamina propria mononuclear cells from the colon. DNA microarray analysis revealed elevated expression of genes associated with immune response and reduced expression of genes with mucosal repair and remodeling in the colon of EP4-deficient mice. We conclude that EP4 maintains intestinal homeostasis by keeping mucosal integrity and downregulating immune response.
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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.