ArticleACS pharmacology & translational science2023
Metabolization of Resolvin E4 by ω-Oxidation in Human Neutrophils: Synthesis and Biological Evaluation of 20-Hydroxy-Resolvin E4 (20-OH-RvE4).
Article in ACS pharmacology & translational science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 9 citations in OpenAlex.
- A Versatile In Vitro Quantitative Assay for Macrophage Efferocytosis in Diverse Research Applications.Bio-protocol · 2026Article
- Splenic erythrophagocytosis is regulated by ALX/FPR2 signaling.Haematologica · 2026Article
- Imaging bioactive lipid isomers in acetaminophen-induced liver injury using nano-DESI tandem MS.Journal of lipid research · 2026Article
- MSC administration resolves experimental acute gout increasing specialized pro-resolving mediators synthesis through a super-induction of prostaglandin EStem cell research & therapy · 2025Article
- Proresolving Lipid Mediators in the Respiratory System.Annual review of physiology · 2025Review
- Role and regulatory mechanism of GPR37 in neurological diseases.Frontiers in cellular neuroscience · 2025Review
- Is Lipid Metabolism of Value in Cancer Research and Treatment? Part II: Role of Specialized Pro-Resolving Mediators in Inflammation, Infections, and Cancer.Metabolites · 2024Review
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Resolvin E4 (RvE4) belongs to the resolvin family of specialized pro-resolving mediators (SPMs). The resolvins are endogenously formed mediators with both potent pro-resolving and anti-inflammatory biological activities and have attracted considerable attention in both inflammation research and drug discovery. Hence, further metabolism of the resolvins is of interest. Gaining knowledge about the structure-function of further metabolites of the resolvins is important due to their interest in drug-discovery efforts. For the first time, the total synthesis and biological evaluations of the ω-20 hydroxylated metabolite of RvE4, named herein 20-OH-RvE4, are presented. RvE4 was converted to 20-OH-RvE4 by human polymorphonuclear leukocytes. LC-MS/MS analysis and UV spectrophotometry reveal that the synthetic 20-OH-RvE4 matched RvE4-converted product 20-OH-RvE4 by human neutrophils. Cellular studies have revealed that RvE4 is formed from eicosapentaenoic acid in physiologic hypoxia by human neutrophils and macrophages, and we herein established that 20-OH-RvE4 is a secondary metabolite formed by the ω-oxidation of RvE4 in human neutrophils. A direct comparison of the biological actions between RvE4 and its metabolic product suggested that 20-OH-RvE4 displayed reduced bioactions in stimulating the efferocytosis of human senescent erythrocytes by human M2-like macrophages. At concentrations down to 0.1 nM, RvE4 increased macrophage erythrophagocytosis, an important pro-resolving function that was diminished due to metabolic transformation. The results provided herein contribute to a novel molecular insight on the further local metabolization of RvE4, the newest member among the SPM superfamily.
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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.