ArticleCells2021
Time-Dependent Protective and Pro-Resolving Effects of FPR2 Agonists on Lipopolysaccharide-Exposed Microglia Cells Involve Inhibition of NF-κB and MAPKs Pathways.
Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- Article
- Toward a Therapy for Autism Spectrum Disorder: The Formyl Peptide Receptor 2 Agonist MR-39 Supports Synaptic Health in the BTBR Mouse and Features a Favorable Safety Profile.ACS pharmacology & translational science · 2026Article
- Reprogramming Inflammatory Macrophages with Specialized Pro-Resolving Lipid Mediators: A Novel Immunotherapeutic Strategy for Asthma.Biomedicines · 2026Review
- Chemokine-Receptor Modulation Shapes Neuroinflammatory and Biomechanical Responses in Organotypic Hippocampal Cultures After Oxygen-Glucose Deprivation.ACS chemical neuroscience · 2026Article
- Carrier-Free Nanocapsule with Dual-Target Capacity for Synergistically Restoring Inflammatory Microenvironment and Microbiota Dysbiosis in Colitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- E3 Ubiquitin Ligase FBXO32 Promotes LPS-Induced Cardiac Injury by Regulating ANXA1/PI3K/AKT Signaling.Inflammation · 2025Article
- Design, Synthesis, and Biological Evaluation of Novel Heteroaryl, Squaramide, and Indolcarboxamide Derivatives as Formyl Peptide Receptor 2 Agonists to Target Neuroinflammation.ACS chemical neuroscience · 2025Article
- Hydrogen Sulfide (HAntioxidants (Basel, Switzerland) · 2025Article
- Microglial Modulation as a Therapeutic Avenue for Perioperative Neurocognitive Disorders: Unveiling Pathophysiological Mechanisms and Clinical Implications.CNS neuroscience & therapeutics · 2025Review
- Inflammaging and Immunosenescence in the Post-COVID Era: Small Molecules, Big Challenges.ChemMedChem · 2025Review
- Prenatal Stress Increases the Risk of the FPR2-related Dysfunction in the Brain's Resolution of Inflammation: A Study on the Humanized APPCurrent neuropharmacology · 2025Article
- Implication of the Annexin 1/FPR axis in leishmanial exosome-mediatedFrontiers in immunology · 2024Article
- Receptors on Microglia.Advances in neurobiology · 2024Review
- Article
- Article
- Article
- The Formyl Peptide Receptor 2 as a Target for Promotion of Resolution of Inflammation.Current neuropharmacology · 2023Article
- Inhibition of Microglial GSK3β Activity Is Common to Different Kinds of Antidepressants: A Proposal for an In Vitro Screen to Detect Novel Antidepressant Principles.Biomedicines · 2023Review
- Downregulated formyl peptide receptor 2 expression in the epileptogenic foci of patients with focal cortical dysplasia type IIb and tuberous sclerosis complex.Immunity, inflammation and disease · 2022Article
- Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Prolonged or excessive microglial activation may lead to disturbances in the resolution of inflammation (RoI). The importance of specialized pro-resolving lipid mediators (SPMs) in RoI has been highlighted. Among them, lipoxins (LXA4) and aspirin-triggered lipoxin A4 (AT-LXA4) mediate beneficial responses through the activation of N-formyl peptide receptor-2 (FPR2). We aimed to shed more light on the time-dependent protective and anti-inflammatory impact of the endogenous SPMs, LXA4, and AT-LXA4, and of a new synthetic FPR2 agonist MR-39, in lipopolysaccharide (LPS)-exposed rat microglial cells. Our results showed that LXA4, AT-LXA4, and MR-39 exhibit a protective and pro-resolving potential in LPS-stimulated microglia, even if marked differences were apparent regarding the time dependency and efficacy of inhibiting particular biomarkers. The LXA4 action was found mainly after 3 h of LPS stimulation, and the AT-LXA4 effect was varied in time, while MR-39's effect was mainly observed after 24 h of stimulation by endotoxin. MR-39 was the only FPR2 ligand that attenuated LPS-evoked changes in the mitochondrial membrane potential and diminished the ROS and NO release. Moreover, the LPS-induced alterations in the microglial phenotype were modulated by LXA4, AT-LXA4, and MR-39. The anti-inflammatory effect of MR-39 on the IL-1β release was mediated through FPR2. All tested ligands inhibited TNF-α production, while AT-LXA4 and MR-39 also diminished IL-6 levels in LPS-stimulated microglia. The favorable action of LXA4 and MR-39 was mediated through the inhibition of ERK1/2 phosphorylation. AT-LXA4 and MR39 diminished the phosphorylation of the transcription factor NF-κB, while AT-LXA4 also affected p38 kinase phosphorylation. Our results suggest that new pro-resolving synthetic mediators can represent an attractive treatment option for the enhancement of RoI, and that FPR2 can provide a perspective as a target in immune-related brain disorders.
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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 Socratic graph.