AI Article Synopsis
- The resolution of acute inflammation involves specialized molecules called pro-resolving mediators, like resolvin D1 (RvD1), which plays a key role by activating the human resolvin D1 receptor (DRV1/GPR32).
- Due to the complex nature of RvD1's synthesis, researchers screened small-molecule libraries and discovered several compounds that effectively activate DRV1, including NCGC00120943 (C1A) and NCGC00135472 (C2A).
- These compounds not only mimic RvD1's function but also enhance the ability of macrophages to clear out pathogens, demonstrating potential as therapeutic agents for inflammation resolution.
Article Abstract
Resolution of acute inflammation is governed, in part, by specialized pro-resolving mediators, including lipoxins, resolvins, protectins, and maresins. Among them, resolvin D1 (RvD1) exhibits potent pro-resolving functions via activating human resolvin D1 receptor (DRV1/GPR32). RvD1 is a complex molecule that requires challenging organic synthesis, diminishing its potential as a therapeutic. Therefore, we implemented a high-throughput screening of small-molecule libraries and identified several chemotypes that activated recombinant DRV1, represented by NCGC00120943 (C1A), NCGC00135472 (C2A), pMPPF, and pMPPI. These chemotypes also elicited rapid impedance changes in cells overexpressing recombinant DRV1. With human macrophages, they each stimulated phagocytosis of serum-treated zymosan at concentrations comparable with that of RvD1, the endogenous DRV1 ligand. In addition, macrophage phagocytosis of live E. coli was significantly increased by these chemotypes in DRV1-transfected macrophages, compared with mock-transfected cells. Taken together, these chemotypes identified by unbiased screens act as RvD1 mimetics, exhibiting pro-resolving functions via interacting with human DRV1.
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Source |
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405215 | PMC |
| http://dx.doi.org/10.1016/j.chembiol.2018.10.023 | DOI Listing |
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