TABLE 7.
Examples of DHA-derived oxylipin functions1
| DHA-derived oxylipin functions | |
| LOX oxylipins | |
| 14,20-DiHDoHE | Inhibits PMN infiltration in the mouse peritonitis model (101) |
| 14,21-DiHDoHE | Enhances wound healing in murine models (313, 314) |
| 4-HDoHE | Inhibits endothelial cell proliferation and sprouting angiogenesis in mouse model of oxygen-induced retinopathy (315) |
| 7-HDoHE | Activates PPARγ in transfected monkey kidney COS-7 cells (316) |
| 13-HDoHE | Inhibits TNFα-induced cytokine production in human microglial cells (26) |
| 14-HDoHE | Inhibits human platelet aggregation (180) |
| 17S-HDoHE | Vasodilates bovine coronary arterial smooth muscle cells (317) |
| Reduces genotoxic and oxidative damage in murine hepatocyte cells and TNFα release by murine macrophages (316) | |
| 17R-HDoHE | Inhibits hyperalgesia in a rat model of adjuvant-induced arthritis (318) |
| Has anti-inflammatory effects in a mouse model of dextran sulfate sodium-induced colitis (319) | |
| Inhibits TNFα-induced cytokine production in human microglial cells (26) | |
| 17-HDoHE | Decreases LPS-induced TNFα secretion in a murine macrophage cell line (304) |
| Inhibits 5-LOX in rat basophilic leukemia cells (82) | |
| 17-HpDoHE | Displays cytotoxic potency in human neuroblastoma cells (320) |
| MaR1 | Anti-inflammatory in a murine model of acute respiratory distress syndrome (321) |
| Reduces inflammation- and chemotherapy-induced neuropathic pain in mice (322) | |
| Mitigates inflammatory effects of LPS-induced lung injury in mouse model (323) | |
| PD1 | Reduces genotoxic and oxidative damage in murine hepatocyte cells and TNFα release by murine macrophages (316) |
| Promotes murine phagocyte removal during acute inflammation in vitro and in vivo (318) | |
| Decreases leukocyte accumulation in a mouse model of kidney injury (324) | |
| Protects human retinal pigment epithelial cells from apoptosis due to oxidative stress (325) | |
| Promotes mouse corneal epithelial cell wound healing (212) | |
| PDX | Reduces inflammation in murine peritonitis and inhibits human microglial cell cytokine expression in vitro (91) |
| Inhibits collagen-, AA-, and thromboxane-induced human platelet aggregation (326) | |
| Inhibits PMN infiltration in mouse model of ischemic stroke (327) | |
| Decreases reactive oxygen species production and COX activity in human neutrophils (328) | |
| Improves insulin sensitivity by raising muscle IL-6 without affecting adipose tissue inflammation in a murine model (329) | |
| RvD1 | Reduces reactivity and Ca2+ sensitivity in overactive human pulmonary artery smooth muscle cells (330) |
| Improves bacterial clearance and survival of mice with cecal ligation and puncture-induced sepsis (331) | |
| RvD2 | Has anti-inflammatory effects in a mouse model of dextran sulfate sodium–induced colitis (319) |
| Improves bacterial clearance and survival of mice with cecal ligation and puncture-induced sepsis (332) | |
| Inhibits inflammatory pain in mice (333) | |
| Mitigates neutrophil-mediated damage in mouse burn model (334) | |
| RvD3 | Reduces peritonitis and dermal inflammation in murine model (335) |
| RvD5 | Enhances phagocyte containment of Escherichia coli in a mouse model (336) |
| AT-RvD1 | Inhibits hyperalgesia in a rat model of adjuvant-induced arthritis (318) |
| Has anti-inflammatory effects in a mouse model of dextran sulfate sodium-induced colitis (319) | |
| AT-RvD3 | Reduces murine peritonitis and dermal inflammation with activity similar to RvD3 (335) |
| CYP oxylipins | |
| 7,8-, 10,11-, 13,14-, 16,17-, 19,20-DiHDPE | Inhibit human platelet aggregation with moderately lower potency to EpDPE, and do not affect thromboxane synthesis (298) |
| 13,14-, 16,17- DiHDPE | Reduce pain associated with inflammation more potently than EpETrE and EpEPE (91) |
| 13,14-DiHDPE | Markedly reduces potency to dilate porcine coronary arterioles compared with parent compound (339) |
| 7,8-, 10,11-, 13,14-, 16,17-, 19,10-EpDPE | Dilates porcine coronary arterioles (337) |
| Inhibits human platelet aggregation and thromboxane synthesis, with potency similar to other EpETE and EpDPE isomers, and greater potency than EpETrE isomers (298) | |
| 16,17-, 19,20-EpDPE | Inhibits Met-1 tumor angiogenesis and growth in mice (231) |
| 19,20-EpDPE | Decreases human platelet aggregation (299) |
1
AA, arachidonic acid; AT, aspirin-triggered; COX, cyclooxygenase; CYP, cytochrome P450; DiHDoHE, dihydroxy-docosahexaenoic acid; DiHDPE, dihydroxy-docosapentaenoic acid; EpDPE, epoxy-docosapentaenoic acid; EpEPE, epoxy-eicosapentaenoic acid; EpETE, epoxy-eicosatetraenoic acid; EpETrE, epoxy-eicosatrienoic acid; HDoHE, hydroxy-docosahexaenoic acid; HpDoHE, hydroperoxy-docosahexaenoic acid; LOX, lipoxygenase; MaR, maresin; PMN, polymorphonuclear leukocyte; Rv, resolvin.