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Functional Metabolomics Reveals Novel Active Products in the DHA Metabolome

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Endogenous mechanisms for successful resolution of an acute inflammatory response and the local return to homeostasis are of interest because excessive inflammation underlies many human diseases. Systematic studies revealed that docosahexaenoic acid (DHA) was converted to DHEA-derived novel bioactive products as well as aspirin-triggered forms of protectins (AT-PD1). The new oxygenated DHEA-derived products blocked PMN chemotaxis, reduced P-selectin expression and platelet-leukocyte adhesion, and showed organ protection in ischemia/reperfusion injury. These products activated cannabinoid receptor (CB2 receptor) and not CB1 receptors. The AT-PD1 reduced neutrophil (PMN) recruitment in murine peritonitis. With human cells, AT-PD1 decreased transendothelial PMN migration as well as enhanced efferocytosis of apoptotic human PMN by macrophages. The recent findings reviewed here indicate that DHEA oxidative metabolism and aspirin-triggered conversion of DHA produce potent novel molecules with anti-inflammatory and organ-protective properties, opening the DHA metabolome functional roles.

The review article is published online in Frontiers in Immunology and is free to access.