CYP450-derived oxylipins mediate inflammatory resolution
Gilroy DW., Edin ML., De Maeyer RPH., Bystrom J., Newson J., Lih FB., Stables M., Zeldin DC., Bishop-Bailey D.
Significance A number of lipid mediators are known to contribute to inflammatory resolution. Fatty acid metabolites of cytochrome P450 (CYP) enzymes are found in abundance; however, their roles in inflammatory resolution are not known. Targeted lipidomics revealed that CYP450-epoxy-oxylipins were present during acute inflammation and inflammatory resolution. Using mice lacking soluble epoxide hydrolase, the major metabolizing pathway for CYP450-derived fatty acid mediators, and CYP450 epoxygenase inhibition specifically during resolution, we show that CYP450-derived lipids dramatically limit the accumulation of inflammatory monocytes during resolution. Moreover, all cells of the monocyte lineage examined showed a dramatic alteration in their proresolution phenotype following epoxygenase inhibition. These findings demonstrate that the CYP450-epoxy-oxylipins pathway has a critical role in monocyte lineage recruitment and resolution activity during inflammatory resolution.