17(R)-Resolvin D3 (17(R)-RvD3) is an aspirin-triggered epimer of resolvin D3 .1 It is produced from docosahexaenoic acid by COX-2 in the presence of aspirin via a 17(R)-hydroperoxy DHA (17(R)-HDHA;) intermediate and has been found in mouse inflammatory exudates.1,2 17(R)-RvD3 reduces transmigration of isolated human polymorphonuclear cells (PMNs) and induces efferocytosis of apoptotic PMNs by macrophages.2 17(R)-RvD3 (10 ng/animal) reduces transmigration of neutrophils into the peritoneal cavity, as well as decreases the levels of IL-6 and increases the levels of IL-10 in inflammatory exudate in a mouse model of zymosan-induced peritonitis. It activates GPR32 in a β-arrestin reporter assay and increases phagocytosis to a greater degree in CHO cells overexpressing GPR32 compared to mock-transfected cells. 17(R)-RvD3 increases phagocytosis of etoposide-generated tumor cell debris by monocyte-derived macrophages in H460 human lung carcinoma cells in a concentration-dependent manner.3 It also inhibits tumor growth in a mouse model of Lewis lung carcinoma when administered at a dose of 0.6 μg/kg per day.
References
1. Winkler, J.W., Uddin, J., Serhan, C.N., et al. Stereocontrolled total synthesis of the potent anti-inflammatory and pro-resolving lipid mediator resolvin D3 and its aspirin-triggered 17R-epimer. Org. Lett. 15(7), 1424-1427 (2013).
2. Dalli, J., Winkler, J.W., Colas, R.A., et al. Resolvin D3 and aspirin-triggered resolvin D3 are potent immunoresolvents. Chem. Biol. 20(2), 188-201 (2013).
3. Gilligan, M.M., Gartng, A., Sulcier, M.L., et al. Aspirin-triggered proresolving mediators stimulate resolution in cancer. Proc. Nat. Acad. Sci. USA 116(13), 6292-6297 (2019).