ArticleMolecular pharmacology2015
EP2 Receptor Signaling Regulates Microglia Death.
Article in Molecular pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 51 citations in OpenAlex.
- Development of highly potent EP2 antagonists as novel anti-inflammatory neuroprotectants.Bioorganic & medicinal chemistry · 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
- NLRX1 Inhibits LPS-Induced Microglial Death via Inducing p62-Dependent HO-1 Expression, Inhibiting MLKL and Activating PARP-1.Antioxidants (Basel, Switzerland) · 2024Article
- Arachidonic acid-derived lipid mediators in multiple sclerosis pathogenesis: fueling or dampening disease progression?Journal of neuroinflammation · 2024Review
- Targeting EP2 Receptor for Drug Discovery: Strengths, Weaknesses, Opportunities, and Threats (SWOT) Analysis.Journal of medicinal chemistry · 2023Review
- 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
- Inducible Prostaglandin E Synthase as a Pharmacological Target for Ischemic Stroke.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- EP2 Antagonists (2011-2021): A Decade's Journey from Discovery to Therapeutics.Journal of medicinal chemistry · 2021Review
- A Novel Second-Generation EP2 Receptor Antagonist Reduces Neuroinflammation and Gliosis After Status Epilepticus in Rats.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Small molecules targeting cyclooxygenase/prostanoid cascade in experimental brain ischemia: Do they translate?Medicinal research reviews · 2021Review
- PGE2 receptors in detrusor muscle: Drugging the undruggable for urgency.Biochemical pharmacology · 2021Review
- Prostaglandin E receptors as targets for ischemic stroke: Novel evidence and molecular mechanisms of efficacy.Pharmacological research · 2021Review
- Inhibition of the prostaglandin EP2 receptor prevents long-term cognitive impairment in a model of systemic inflammation.Brain, behavior, & immunity - health · 2020Article
- Dynamic Change of Shanks Gene mRNA Expression and DNA Methylation in Epileptic Rat Model and Human Patients.Molecular neurobiology · 2020Article
- Inhibiting the PGEACS pharmacology & translational science · 2020Article
- Caffeine prevents prostaglandin EAmerican journal of physiology. Regulatory, integrative and comparative physiology · 2020Article
- Inverse Agonism of Cannabinoid Receptor Type 2 Confers Anti-inflammatory and Neuroprotective Effects Following Status Epileptics.Molecular neurobiology · 2020Article
- Targeting prostaglandin receptor EP2 for adjunctive treatment of status epilepticus.Pharmacology & therapeutics · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 3 countries.
Funding
Abstract
The timely resolution of inflammation prevents continued tissue damage after an initial insult. In the brain, the death of activated microglia by apoptosis has been proposed as one mechanism to resolve brain inflammation. How microglial death is regulated after activation is still unclear. We reported that exposure to lipopolysaccharide (LPS) and interleukin (IL)-13 together initially activates and then kills rat microglia in culture by a mechanism dependent on cyclooxygenase-2 (COX-2). We show here that activation of the E prostanoid receptor 2 (EP2, PTGER2) for prostaglandin E2 mediates microglial death induced by LPS/IL-13, and that EP2 activation by agonist alone kills microglia. Both EP2 antagonists and reactive oxygen scavengers block microglial death induced by either LPS/IL-13 or EP2 activation. By contrast, the homeostatic induction of heme oxygenase 1 (Hmox1) by LPS/IL-13 or EP2 activation protects microglia. Both the Hmox1 inducer cobalt protoporphyrin and a compound that releases the Hmox1 product carbon monoxide (CO) attenuated microglial death produced by LPS/IL-13. Whereas CO reduced COX-2 protein expression, EP2 activation increased Hmox1 and COX-2 expression at both the mRNA and protein level. Interestingly, caspase-1 inhibition prevented microglial death induced by either LPS/IL-13 or low (but not high) concentrations of butaprost, suggestive of a predominantly pyroptotic mode of death. Butaprost also caused the expression of activated caspase-3 in microglia, pointing to apoptosis. These results indicate that EP2 activation, which initially promotes microglial activation, later causes delayed death of activated microglia, potentially contributing to the resolution phase of neuroinflammation.
Indexed as
Identifiers
What OpenQuestion holds
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.