Metabolization of Resolvin E4 by ω-Oxidation in Human Neutrophils: Synthesis and Biological Evaluation of 20-Hydroxy-Resolvin E4 (20-OH-RvE4)

efferocytosis
DOI: 10.1021/acsptsci.3c00201 Publication Date: 2023-11-20T18:37:26Z
ABSTRACT
Resolvin E4 (RvE4) belongs to the resolvin family of specialized pro-resolving mediators (SPMs). The resolvins are endogenously formed with both potent and anti-inflammatory biological activities have attracted considerable attention in inflammation research drug discovery. Hence, further metabolism is interest. Gaining knowledge about structure–function metabolites important due their interest drug-discovery efforts. For first time, total synthesis evaluations ω-20 hydroxylated metabolite RvE4, named herein 20-OH-RvE4, presented. RvE4 was converted 20-OH-RvE4 by human polymorphonuclear leukocytes. LC–MS/MS analysis UV spectrophotometry reveal that synthetic matched RvE4-converted product neutrophils. Cellular studies revealed from eicosapentaenoic acid physiologic hypoxia neutrophils macrophages, we established a secondary ω-oxidation A direct comparison actions between its metabolic suggested displayed reduced bioactions stimulating efferocytosis senescent erythrocytes M2-like macrophages. At concentrations down 0.1 nM, increased macrophage erythrophagocytosis, an function diminished transformation. results provided contribute novel molecular insight on local metabolization newest member among SPM superfamily.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (42)
CITATIONS (3)