ArticleThe American journal of pathology2011
The melanocortin agonist AP214 exerts anti-inflammatory and proresolving properties.
Article in The American journal of pathology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 80 citations in OpenAlex.
- ABT-719 for the Prevention of Acute Kidney Injury in Patients Undergoing High-Risk Cardiac Surgery: A Randomized Phase 2b Clinical Trial.Journal of the American Heart Association · 2016Trial
- Resolution Pharmacology: State-of-the-art and therapeutic landscape.Pharmacological reviews · 2025Review
- Polymorphism of Melanocortin Receptor Genes-Association with Inflammatory Traits and Diseases.Diseases (Basel, Switzerland) · 2025Review
- Stimulating the Melanocortin System in Uveitis and Diabetes Preserves the Structure and Anti-Inflammatory Activity of the Retina.International journal of molecular sciences · 2023Article
- Melanocortin receptor agonists suppress experimental autoimmune uveitis.Experimental eye research · 2022Article
- G-Protein-Coupled Receptors in Rheumatoid Arthritis: Recent Insights into Mechanisms and Functional Roles.Frontiers in immunology · 2022Review
- Melanocortin therapies to resolve fibroblast-mediated diseases.Frontiers in immunology · 2022Review
- Pro-resolving and anti-arthritic properties of the MCFrontiers in immunology · 2022Article
- New promising drugs for the treatment of systemic sclerosis: pathogenic considerations, enhanced classifications, and personalized medicine.Expert opinion on investigational drugs · 2021Review
- Antifibrotic and Anti-Inflammatory Actions of α-Melanocytic Hormone: New Roles for an Old Player.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Uncovering the Oral Dysbiotic Microbiota as Masters of Neutrophil Responses in the Pathobiology of Periodontitis.Frontiers in microbiology · 2021Review
- Pro-Resolving Ligands Orchestrate Phagocytosis.Frontiers in immunology · 2021Review
- Repository corticotropin injection attenuates collagen-induced arthritic joint structural damage and has enhanced effects in combination with etanercept.BMC musculoskeletal disorders · 2020Article
- Therapeutic senescence via GPCR activation in synovial fibroblasts facilitates resolution of arthritis.Nature communications · 2020Article
- Cyclic AMP Regulates Key Features of Macrophages via PKA: Recruitment, Reprogramming and Efferocytosis.Cells · 2020Article
- Activation of Melanocortin Receptors as a Potential Strategy to Reduce Local and Systemic Reactions Induced by Respiratory Viruses.Frontiers in endocrinology · 2020Review
- Cosyntropin Attenuates Neuroinflammation in a Mouse Model of Traumatic Brain Injury.Frontiers in molecular neuroscience · 2020Article
- ROCK Inhibition Drives Resolution of Acute Inflammation by Enhancing Neutrophil Apoptosis.Cells · 2019Article
- Plasminogen and the Plasminogen Receptor, Plg-RFrontiers in immunology · 2019Article
- Melanocortin Regulation of Inflammation.Frontiers in endocrinology · 2019Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synthetic and natural melanocortin (MC) peptides afford inhibitory properties in inflammation and tissue injury, but characterization of receptor involvement is still elusive. We used the agonist AP214 to test MC-dependent anti-inflammatory effects. In zymosan peritonitis, treatment of mice with AP214 (400 to 800 μg/kg) inhibited cell infiltration, an effect retained in MC receptor type 1, or MC(1), mutant mice but lost in MC(3) null mice. In vitro, cytokine release from zymosan-stimulated macrophages was affected by AP214, with approximately 80%, 30%, and 40% reduction in IL-1β, tumor necrosis factor-α, and IL-6, respectively. Inhibition of IL-1β release was retained in MC(1) mutant cells but was lost in MC(3) null cells. Furthermore, AP214 augmented uptake of zymosan particles and human apoptotic neutrophils by wild-type macrophages: this proresolving property was lost in MC(3) null macrophages. AP214 displayed its pro-efferocytotic effect also in vivo. Finally, in a model of inflammatory arthritis, AP214 evoked significant reductions in the clinical score. These results indicate that AP214 elicits anti-inflammatory responses, with a preferential effect on IL-1β release. Furthermore, we describe for the first time a positive modulation of an MC agonist on the process of efferocytosis. In all cases, endogenous MC(3) is the receptor that mediates these novel properties of AP214. These findings might clarify the tissue-protective properties of AP214 in clinical settings and may open further development for novel MC agonists.
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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.