ArticleThe Journal of biological chemistry2013
EP2 receptor signaling pathways regulate classical activation of microglia.
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. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 101 citations in OpenAlex.
- Prostaglandins: Key players in immunomodulation of the nervous system.Neural regeneration research · 2026Article
- Mast Cells in the Developing Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Review
- Development of highly potent EP2 antagonists as novel anti-inflammatory neuroprotectants.Bioorganic & medicinal chemistry · 2026Article
- Cannabinoid receptor-2 ligand beta-caryophyllene modulates inflammatory responses of bovine peripheral blood mononuclear cells in vitro.Scientific reports · 2026Article
- Neuroinflammation and Disease: Pathways and Opportunities.Annual review of pharmacology and toxicology · 2026Review
- Brain-invading monocytes promote seizure-associated cognitive deficits and neurodegeneration.Neuropharmacology · 2025Article
- Spatial mapping of the AA-PGEActa neuropathologica · 2025Article
- The role of n-3-derived specialised pro-resolving mediators (SPMs) in microglial mitochondrial respiration and inflammation resolution in Alzheimer's disease.Molecular neurodegeneration · 2025Review
- Impairment of neuronal tyrosine phosphatase STEP worsens post-ischemic inflammation and brain injury under hypertensive condition.Journal of neuroinflammation · 2024Article
- Mitigation of CXCL10 secretion by metabolic disorder drugs in microglial-mediated neuroinflammation.Journal of neuroimmunology · 2024Article
- Microglia in neuroimmunopharmacology and drug addiction.Molecular psychiatry · 2024Review
- Arachidonic acid-derived lipid mediators in multiple sclerosis pathogenesis: fueling or dampening disease progression?Journal of neuroinflammation · 2024Review
- Receptors on Microglia.Advances in neurobiology · 2024Review
- Targeting EP2 Receptor for Drug Discovery: Strengths, Weaknesses, Opportunities, and Threats (SWOT) Analysis.Journal of medicinal chemistry · 2023Review
- The discovery of cyclic γ-AApeptides as the promising ligands targeting EP2.Bioorganic & medicinal chemistry letters · 2023Article
- Neuroinflammatory mediators in acquired epilepsy: an update.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- Preclinical development of an EP2 antagonist for post-seizure cognitive deficits.Neuropharmacology · 2023Article
- Increase in Cellular Lysophosphatidylserine Content Exacerbates Inflammatory Responses in LPS-Activated Microglia.Neurochemical research · 2022Article
- Article
- Second-Generation Prostaglandin Receptor EP2 Antagonist, TG8-260, with High Potency, Selectivity, Oral Bioavailability, and Anti-Inflammatory Properties.ACS pharmacology & translational science · 2022Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Activation of EP2 receptors by prostaglandin E2 (PGE2) promotes brain inflammation in neurodegenerative diseases, but the pathways responsible are unclear. EP2 receptors couple to Gαs and increase cAMP, which associates with protein kinase A (PKA) and cAMP-regulated guanine nucleotide exchange factors (Epacs). Here, we studied EP2 function and its signaling pathways in rat microglia in their resting state or undergoing classical activation in vitro following treatment with low concentrations of lipopolysaccharide and interferon-γ. Real time PCR showed that PGE2 had no effect on expression of CXCL10, TGF-β1, and IL-11 and exacerbated the rapid up-regulation of mRNAs encoding cyclooxygenase-2, inducible NOS, IL-6, and IL-1β but blunted the production of mRNAs encoding TNF-α, IL-10, CCL3, and CCL4. These effects were mimicked fully by the EP2 agonist butaprost but only weakly by the EP1/EP3 agonist 17-phenyl trinor PGE2 or the EP4 agonist CAY10598 and not at all by the EP3/EP1 agonist sulprostone and confirmed by protein measurements of cyclooxygenase-2, IL-6, IL-10, and TNF-α. In resting microglia, butaprost induced cAMP formation and altered the mRNA expression of inflammatory mediators, but protein expression was unchanged. The PKA inhibitor H89 had little or no effect on inflammatory mediators modulated by EP2, whereas the Epac activator 8-(4-chlorophenylthio)-2'-O-methyladenosine 3',5'-cyclic monophosphate acetoxymethyl ester mimicked all butaprost effects. These results indicate that EP2 activation plays a complex immune regulatory role during classical activation of microglia and that Epac pathways are prominent in this role.
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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.