ArticleBritish journal of pharmacology2010
A novel antagonist of the prostaglandin E(2) EP(4) receptor inhibits Th1 differentiation and Th17 expansion and is orally active in arthritis models.
Article in British journal of pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 94 citations in OpenAlex.
- Gut microbiota in chronic inflammation: the interplay with lipid mediators.Gut microbes · 2026Review
- Unveiling Novel Drug Targets and Emerging Therapies for Rheumatoid Arthritis: A Comprehensive Review.ACS pharmacology & translational science · 2024Review
- Quantification of Grapiprant and Its Stability Testing under Changing Environmental Conditions.Biomedicines · 2022Article
- Diversified Effects of COVID-19 as a Consequence of the Differential Metabolism of Phospholipids and Lipid Peroxidation Evaluated in the Plasma of Survivors and Deceased Patients upon Admission to the Hospital.International journal of molecular sciences · 2022Article
- Pharmacokinetics of grapiprant and effects on TNF-alpha concentrations following oral administration to horses.Journal of veterinary pharmacology and therapeutics · 2022Article
- Targeting Lineage-Specific Transcription Factors and Cytokines of the Th17/Treg Axis by Novel 1,3,4-Oxadiazole Derivatives of Pyrrolo[3,4-International journal of molecular sciences · 2022Article
- Single-cell analysis of prostaglandin E2-induced human decidual cell in vitro differentiation: a minimal ancestral deciduogenic signal†.Biology of reproduction · 2022Article
- Blockade of prostaglandin E2 receptor 4 ameliorates peritoneal dialysis-associated peritoneal fibrosis.Frontiers in pharmacology · 2022Article
- Prostaglandin EImmunology · 2021Article
- Grapiprant: A snapshot of the current knowledge.Journal of veterinary pharmacology and therapeutics · 2021Review
- Role of arachidonic cascade in COVID-19 infection: A review.Prostaglandins & other lipid mediators · 2021Review
- Bioactive Lipids in MSCs Biology: State of the Art and Role in Inflammation.International journal of molecular sciences · 2021Review
- Regulation of T-Cell Immune Responses by Pro-Resolving Lipid Mediators.Frontiers in immunology · 2021Review
- Prostanoids and Resolution of Inflammation - Beyond the Lipid-Mediator Class Switch.Frontiers in immunology · 2021Review
- Promising Therapeutic Targets for Treatment of Rheumatoid Arthritis.Frontiers in immunology · 2021Review
- International Union of Basic and Clinical Pharmacology. CIX. Differences and Similarities between Human and Rodent Prostaglandin EPharmacological reviews · 2020Article
- Prostaglandin-cytokine crosstalk in chronic inflammation.British journal of pharmacology · 2019Review
- Pharmacological characterisation of CR6086, a potent prostaglandin EArthritis research & therapy · 2018Article
- Bioactive Lipids and Chronic Inflammation: Managing the Fire Within.Frontiers in immunology · 2018Review
- Article
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeRheumatoid arthritis (RA) is an autoimmune disorder involving subsets of activated T cells, in particular T helper (Th) 1 and Th17 cells, which infiltrate and damage tissues and induce inflammation. Prostaglandin E(2) (PGE(2)) enhances the Th17 response, exacerbates collagen-induced arthritis (CIA) and promotes inflammatory pain. The current study investigated whether selective antagonism of the PGE(2) EP(4) receptor would suppress Th1/Th17 cell development and inflammatory arthritis in animal models of RA. EXPERIMENTAL APPROACH: Effects of PGE(2) and a novel EP(4) receptor antagonist ER-819762 on Th1 differentiation, interleukin-23 (IL-23) production by dendritic cells (DCs), and Th17 development were assessed in vitro. The effect of ER-819762 was evaluated in CIA and glucose-6-phosphate isomerase (GPI)-induced arthritis models. In addition, the effects of ER-819762 on pain were evaluated in a model of chronic inflammatory pain induced by complete Freund's adjuvant (CFA) in the rat. KEY
resultsStimulation of the EP(4) receptor enhanced Th1 differentiation via phosphatidylinositol 3 kinase signalling, selectively promoted Th17 cell expansion, and induced IL-23 secretion by activated DCs, effects suppressed by ER-819762 or anti-PGE(2) antibody. Oral administration of ER-19762 suppressed Th1 and Th17 cytokine production, suppressed disease in collagen- and GPI-induced arthritis in mice, and suppressed CFA-induced inflammatory pain in rats. CONCLUSION AND IMPLICATIONS: PGE(2) stimulates EP(4) receptors to promote Th1 differentiation and Th17 expansion and is critically involved in development of arthritis in two animal models. Selective suppression of EP(4) receptor signalling may have therapeutic value in RA both by modifying inflammatory arthritis and by relieving pain.
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