Figure 1.

Metabolic route of ω-6- and ω-3-derived lipid mediators. (A) Essential fatty acid linoleic acid, classified as ω-6 polyunsaturated fatty acid, can be converted into arachidonic acid (AA). In turn, AA is metabolized in hydroxy-eicosatetraenoic acids (HETEs) and epoxy-eicosatrienoic acids (EETs) via cytochrome P450 (CYP450). Via lipoxygenase (LOX) pathway, AA is converted to lipoxins (LXs) and leukotriens (LTs), whereas via cyclooxygenase it is metabolized in prostaglandins (PGs) and tromboxanes (TBXs). HETEs, EETs, PGs, TBXs, and LTs are all pro-inflammatory, while LXs are considered pro-resolving mediators. (B) Essential fatty acid α-linolenic acid is converted to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA and DHA may be substrate of CYP450, resulting into production of E-series resolvins (Rv) and epoxides, respectively. In addition, DHA is metabolized via LOX to D-series Rv, maresins, and protectins. All these EPA- and DHA-derived mediators are recognized to harbor pro-resolving properties.