Specialized pro-resolving mediators

464:) may reflect, in part, a failure in this class switching. Diseases caused or worsened by non-adaptive inflammatory responses may by amenable to treatment with SPM or synthetic SPM which, unlike natural SPM, resist in vivo metabolic inactivation. The SPM possess overlapping activities which work to resolve inflammation. SPMs (typically more than one for each listed action) have the following anti-inflammatory activities on the indicated cell types as defined in animal and human model studies: 1793:-RvDs, aspirin-triggered-RvDs, or AT-RvDs 1 thru 6. In certain cases, the final structures of these AT-RvDs is assumed by analogy to the structures of their RvD counterparts. Studies have found that most (and presumably all) of these metabolites have potent anti-inflammatory activity in vitro and/or in animal models. The following table lists the structural formulae, major activities with citations and cellular receptor targets of D series resolvins. 2603:, and possessing the ability to inhibit the influx of leukocytes into the peritoneum of the mice. Finally, two resolvin sulfido-conjugates (8-glutathionyl,7,17-dihydroxy-4Z,9,11,13Z,15E,19Z-docosahexaenoic acid and 8-cysteinylglycinyl,7,17-dihydroxy-4Z,9,11,13Z,15E,19Z-docosahexaenoic acid) have been shown to be formed from their 7,17-dihydroxy precursor by cells in vitro, to accelerate regeneration of experimental injuries in 3558:-DHA, while not detected by in the mouse model of peritonitis or stimulated leukocytes, is more potent than even PD1 in inhibiting peritonitis in the mouse model. In addition to these compounds, two protectin sulfido-conjugates (16-glutathionyl,17-hydroxy-4Z,7Z,10,12,14,19Z-docosahexaenoic acid and 16-cysteinylglycinyl,17-hydroxy-4Z,7Z,10,12,14,19Z-docosahexaenoic acid) form in vitro, accelerate regeneration of injured 440:) which instruct relevant cells to produce SPM and to assume a more anti-inflammatory phenotype. Resolution of the normal inflammatory response, then, may involve switching production of pro-inflammatory to anti-inflammatory PUFA metabolites. Excessive inflammatory responses to insult as well as many pathological inflammatory responses that contribute to diverse diseases such as 398:. The cited cells then proceeded to neutralize invading organisms, limit tissue injury, and initiate tissue repair. Hence, the classic inflammatory response was viewed as fully regulated by the soluble signaling agents. That is, the agents formed, orchestrated an inflammatory cell response, but then dissipated to allow resolution of the response. In 1974, however, 25: 423:

causing the resolution of inflammation. In this view, inflammatory responses are not self-limiting but rather limited by the formation of a particular group of PUFA metabolites that counteract the actions of pro-inflammatory signals. Later, these PUFA metabolites were classified together and termed specialized pro-resolving mediators (i.e. SPM).

4603:; they are then release from the phospholipids to become free in attacking their target proteins. All four products have been shown to form and possess SPM activity in various in vitro studies of human and animal tissue as well as in in vivo studies of animal models of inflammation; they have been termed pro-resolving mediators of inflammation 3157:. While its in vivo synthetic pathway has not been defined, 10-epi-PD1 has anti-inflammatory activity. The following table lists the structural formulae (DHA stands for docosahexaenoic acid), major activities, cellular receptor targets (where known), and Knowledge pages giving further information on the activity and syntheses. 432:

these cells to produce SPM which feed back on their parent and other cells to dampen their pro-inflammatory activity and to promote repair. Resolution of an inflammatory response is thus an active rather than self-limiting process which is set into motion at least in part by the initiating pro-inflammatory mediators (e.g.

422:

activity suggesting that they might act as pro-inflammatory agents, Serhan and colleagues and other groups found that the lipoxins as well as a large number of newly discovered metabolites of other PUFA possess primarily if not exclusively anti-inflammatory activities and therefore may be crucial for

4642:

injury. These studies indicate that the suppression of inflammation is a major function of 12/15-lipoxygenase and Alox5 along with the SPMs they make in at least certain rodent experimental inflammation models; although these rodent lipoxygenases differ from human ALOX15 and ALOX5 in the profile of

4698:

syndrome; along with this study, other clinical trials (NCT01639846, NCT01675570, NCT00799552 and NCT02329743) using an RvE1 analogue to treat various ocular conditions are underway. RvE1, Mar1, and NPD1 are in clinical development studies for the treatment of neurodegenerative diseases and hearing

167:

The absolute as well as relative roles of the SPM along with other physiological anti-inflammatory agents in resolving human inflammatory responses remain to be defined precisely. However, studies suggest that synthetic SPM that are resistant to being metabolically inactivated hold promise of being

2499:

ion channel located on the plasma membrane of many human cell types; TRPV4, also termed the vanilloid-receptor related osmotically activated channel (VR-OAC) and OSM9-like transient receptor potential channel member 4 (OTRPC4)2], is involved in multiple physiologic functions and dysfunctions. With

172:

inflammatory responses along with the tissue destruction and morbidity that these responses cause. Based on animal model studies, the inflammation-based diseases which may be treated by such metabolically resistant SPM analogs include not only pathological and tissue damaging responses to invading

431:

The production and activities of the SPM suggest a new view of inflammation wherein the initial response to foreign organisms, tissue injury, or other insults involves numerous soluble cell signaling molecules that not only recruit various cell types to promote inflammation but concurrently cause

2685:

metabolites termed resolvin T1 (RvT1), RvT2, RvT3, and RvT4. These T series resolvins also form in mice undergoing experimental inflammatory responses and have potent in vitro and in vivo anti-inflammatory activity; they are particularly effective in reducing the systemic inflammation as well as

4186:

have been found to possess anti-inflammatory activity in in vitro assays of human neutrophil function. These n−3 DPA-derived maresins have not been defined with respect to the chirality of their hydroxyl residues or the cis–trans isomerism of their double bonds. The following table lists the

3781:

and then metabolized through the cited epoxide-forming pathways to Mar-L1 and MaR-L2. Studies have found that these metabolites have potent anti-inflammatory activity in vitro and in animal models. The following table lists the structural formulae (DHA stands for docosahexaenoic acid), major

4670:, 18-hydroxyeicosapentaenoic acid, 17-hydroxydocosahexaenoic acid, and 14-hydroxydocosahexaenoic. These results support the notion that Cyp1 enzymes contribute to the production of certain SPMs and inflammatory responses in mice; CYP1 enzymes may therefore play a similar role in humans. 4620:. These mice also show an accelerated rate of progression of atherosclerosis whereas mice made to overexpress 12/15-lipoxygenase exhibit a delayed rate of atherosclerosis development. Alox15 overexpressing rabbits exhibited reduced tissue destruction and bone loss in a model of 4578:

from stimulating the transcription of genes that encode various pro-inflammatory proteins. One or both of these mechanisms appears to contribute to the ability of certain highly reactive PUFA-cyclopenetenones to exhibit SPM activity. The PUFA-cyclopentenones include two

3585:, respectively. These products are presumed to be formed in mammals by the metabolism of n−3 DPA by an unidentified 15-lipoxygenase activity to 16,17-epoxide intermediate and the subsequent conversion of this intermediate to the di-hydroxyl products PD1 1354:-RvE2, however has little or no SPM activity and is therefore not considered to be a SPM here. The following table lists the structural formulae (EPA stands for eicosapentaenoic acid), major activities, and cellular receptor targets (where known). 3494:-DHA, is a relatively abundant metabolite compared to PD1 detected in the peritoneal fluid from a mouse model of peritonitis (although not detected in stimulated leukocytes) and has moderately potent anti-inflammatory activity in this model; 10 4557:

protein complex in the cytosol of cells. This negates KEAP1's ability to bind NFE2L2; in consequence, NFE2L2 becomes free to translocate to the nuclease and stimulate the transcription of genes that encode proteins active in detoxifying

4643:

the PUFA metabolites that they make as well as various other parameters (e.g. tissue distribution), these genetic studies allow that human ALOX15, ALOX5, and the SPMs they make may play a similar anti-inflammatory functions in humans.

4650:

enzymes in mice, i.e. Cyp1a1, Cyp1a2, and Cyp1b1, caused an increase in the recruitment of neutrophils to the peritoneum in mice undergoing experimental peritonitis; these triple knockout mice also exhibited an increase in the

3136:

enzyme. While omega-oxidation products of most bioactive PUFA metabolites are far weaker than their precursors, 22-hydroxy-PD1 is as potent as PD1 in inflammatory assays. Aspirin-triggered-PD1 (AT-PD1 or AP-NPD1) is the

4611:

Mice made deficient in their 12/15-lipoxygenase gene (Alox15) exhibit a prolonged inflammatory response along with various other aspects of a pathologically enhanced inflammatory response in experimental models of

4533:. Both compounds possess anti-inflammatory activity in vitro; 15-HEDPEA also has tissue-protective effects in mouse models of lung injury and tissue reperfusion. Like anandamide, both compounds activated the 901:

of their 15-hydroxyl residue. Numerous studies have found that these metabolites have potent anti-inflammatory activity in vitro and in animal models and in humans may stimulate cells by binding to certain

3605:

has anti-inflammatory activity in an in vitro model. The following table lists the structural formulae (DPA stands for docosapentaenoic acid), major activities and cellular receptor targets (where known).

5984: 5789:

Chiang N, Serhan CN, Dahlén SE, Drazen JM, Hay DW, Rovati GE, Shimizu T, Yokomizo T, Brink C (2006). "The lipoxin receptor ALX: potent ligand-specific and stereoselective actions in vivo".

6903:

Balas L, Guichardant M, Durand T, Lagarde M (2014). "Confusion between protectin D1 (PD1) and its isomer protectin DX (PDX). An overview on the dihydroxy-docosatrienes described to date".

4166:−3 DPA by an undefined 12-lipoxygenase activity to a 14-hydroperoxy-DPA intermediated and the subsequent conversion of this intermediate to di-hydroxyl products which have been termed MaR1 1338:-RvE3) isomers, both of which, similar to the other aforementioned metabolites possess potent SPM activity in in vitro and/or animal models. In vitro studies find that ALOX5 can convert 18 2712:

of their double bonds but do possess potent anti-inflammatory activity in animal models and human cells; they also have protective actions in increasing the survival of mice subjected to

3124:

to protectin D1 (PD1, also termed neuroprotectin D1 when formed in neural tissue). PDX is formed by the metabolism of DHA by two serial lipoxygenases, probably a 15-lipoxygenase and

6313:

Klein CP, Sperotto ND, Maciel IS, Leite CE, Souza AH, Campos MM (2014). "Effects of D-series resolvins on behavioral and neurochemical changes in a fibromyalgia-like model in mice".

4549:

structure are chemically reactive and can form adducts with various tissue targets, particularly proteins. Certain of these PUFA-cyclopentenones bind to the sulfur residues in the

6134:

Weylandt KH, Chiu CY, Gomolka B, Waechter SF, Wiedenmann B (2012). "Omega-3 fatty acids and their lipid mediators: towards an understanding of resolvin and protectin formation".

3526:-DHA, is a prominent metabolite detected in stimulated leukocytes, not detected the mouse peritonitis model, and has modest anti-inflammatory activity in the latter model; and 10 906:

on these cells. The following table lists the structural formulae (ETE stands for eicosatetraenoic acid), major activities, and cellular receptor targets (where known).

4510: 43: 7380:

Divanovic S, Dalli J, Jorge-Nebert LF, Flick LM, Gálvez-Peralta M, Boespflug ND, Stankiewicz TE, Fitzgerald JM, Somarathna M, Karp CL, Serhan CN, Nebert DW (2013).

4595:, which is induced in many cell types during inflammation. Both isoprostanes form non-enzymatically as a result the attack on the arachidonic acid bond to cellular 3577:−3 DPA-derived protectins with structural similarities to PD1 and PD2 have been described, determined to be formed in vitro and in animal models, and termed PD1 1648:, and dendritic cells as well as in vascular tissue; GPR32 (also termed the RvD1 receptor or DRV1) is expressed on human inflammation-regulating neutrophils, 4525:) is metabolized to 10,17-dihydroxydocosahexaenoyl ethanolamide (10,17-diHDHEA) and/or 15-hydroxy-16(17)-epoxy-docosapentaenoyl ethanolamide (15-HEDPEA) by 252:

reactions to invading foreign organisms, tissue injuries, and other insults. These reactions were orchestrated by various soluble signaling agents such as

4332:

The following PUFA metabolites, while not yet formally classified as SPM, have been recently described and determined to have anti-inflammatory activity.

2719:. The following table lists the structural formulae (DPA stands for docosapentaenoic acid), major activities and cellular receptor targets (where known). 793:). SPM act, at least in part, by either activating or inhibiting cells through binding to and thereby activating or inhibiting the activation of specific 4624:. Similarly, Alox5 deficient mice exhibit a worsened inflammatory component, failure to resolve, and/or decrease in survival in experimental models of 2563:-docosahexaenoic acid (17-HDHA). 17-HDHA has potent anti-inflammatory activity and has been classified as a SPM although not a resolvin. Similarly, 14 6990:"Structure-function relationships of non-cyclic dioxygenase products from polyunsaturated fatty acids: poxytrins as a class of bioactive derivatives" 5282:"The Protectin Family of Specialized Pro-resolving Mediators: Potent Immunoresolvents Enabling Innovative Approaches to Target Obesity and Diabetes" 597:: inhibit their infiltration into inflamed tissues and release of pro-inflammatory cytokines; stimulate their conversion from a pro-inflammatory M1 264: 6407:"The specialized proresolving mediator 17-HDHA enhances the antibody-mediated immune response against influenza virus: a new class of adjuvant?" 5110:

Serhan CN, Hamberg M, Samuelsson B (1984). "Trihydroxytetraenes: a novel series of compounds formed from arachidonic acid in human leukocytes".

7033:"Anti-inflammatory actions of neuroprotectin D1/protectin D1 and its natural stereoisomers: assignments of dihydroxy-containing docosatrienes" 3733:

activity (which ALOX 12 and mouse 12/15-lipoxygenase possess) to MaR1 and MaR2. During this metabolism, cells also form 7-epi-Mar1, i.e. the 7

177:

but also a wide array of pathological conditions in which inflammation is a contributing factor such as allergic inflammatory diseases (e.g.

7429:

Wu SH, Chen XQ, Liu B, Wu HJ, Dong L (2013). "Efficacy and safety of 15(R/S)-methyl-lipoxin A(4) in topical treatment of infantile eczema".

2704:, have been named based on their presumed structural analogies to the DHA-derived resolvins RvD1, RvD2, and RvD5, respectively. These three 1781:-DHA which is then hydrolyzed to 4,11,17-trihydroxy and 4,5,17-trihydroxy products, RvD3 and RvD4, respectively. These six RvDs possess a 17 1290:-hydroxy-EPA; the later product may be reduced to its 5,18-dihydroxy product, RvE2, or converted to its 5,6-epoxide and then acted on by an 414:

viz., 5,6,15-trihydroxy-7,9,11,13-icosatetraenoic acid and 5,14,15-trihydroxy-6,8,10,12-icosatetraenoic acid. These products are now termed

148:(an inhibitor of formation of pro-inflammatory metabolites of polyunsaturated fatty acids, and the gaseous resolvins, carbon monoxide (see 4147:

The TRPV1 receptor is discussed in the EPA-derived resolvin section; the TRPA1 receptor is discussed in the DHA-derived resolvin section.

6679:

Weylandt KH (2015). "Docosapentaenoic acid derived metabolites and mediators - The new world of lipid mediator medicine in a nutshell".

2495:

The distribution and major functions of GPR32, FPR2, TRPV1, and TRPV3 are given in the above EPA-derived resolvins section; TRPA1 is a

7139:"Maresin-like lipid mediators are produced by leukocytes and platelets and rescue reparative function of diabetes-impaired macrophages" 1644:

along with certain other pro-inflammatory agents and is expressed on human neutrophils, eosinophils, monocytes, macrophages, T cells,

137: 61: 6278:

Farooqui AA (2012). "n-3 fatty acid-derived lipid mediators in the brain: new weapons against oxidative stress and inflammation".

1155:, monocytes, macrophages, and vascular tissue. Both of these receptors are involved in regulating inflammation. The AHR (i.e. the 2595:-docosahexaenoic acid, while not yet assigned a RvD number, qualifies as a RvD-related SPM. It is a DHA metabolite made by mouse 1701:

monooxygenase(s) (bacteria may supply the cytochrome P450 activity in infected tissues) or aspirin-treated cyclooxygenase-2 to 17

355: 240:

and have been proposed to be responsible for the anti-inflammatory actions that are attributed to omega−3 fatty acid-rich diets.

4667: 3149:-hydroxy-DHA and its subsequent metabolism possibly in manner similar to that which forms PD1. 10-Epi-PD1 (ent-AT-NPD1), the 10 910: 6035:"Pro-resolving actions and stereoselective biosynthesis of 18S E-series resolvins in human leukocytes and murine inflammation" 5601:"Novel Endogenous Proresolving Molecules:Essential Fatty Acid-Derived and Gaseous Mediators in the Resolution of Inflammation" 646: 4663: 6953:

Balas L, Durand T (2016). "Dihydroxylated E,E,Z-docosatrienes. An overview of their synthesis and biological significance".

5703:

Romano M, Cianci E, Simiele F, Recchiuti A (2015). "Lipoxins and aspirin-triggered lipoxins in resolution of inflammation".

5384:"Protectins and maresins: New pro-resolving families of mediators in acute inflammation and resolution bioactive metabolome" 4449:; the former two metabolites have been shown to possess anti-inflammatory activity in in vitro and in animal model studies. 4187:

structural formulae (DPA stands for docosapentaenoic acid), major activities and cellular receptor targets (where known).

7382:"Contributions of the three CYP1 monooxygenases to pro-inflammatory and inflammation-resolution lipid mediator pathways" 2642:-docosapentaenoic acid)-derived resolvins are recently identified SPM. In the model system used to identify them, human 339: 194: 5653:

Calder PC (2015). "Marine omega-3 fatty acids and inflammatory processes: Effects, mechanisms and clinical relevance".

1620:

receptor-like 1), also termed the ChemR23 or E series resolvin receptor (ERV), is expressed on inflammation-regulating

577:

of the natural killer cell type of lymphocytes by, e.g. promoting their ability to induce apoptosis in neutrophils and

4691: 4679: 4625: 363: 1765:-DHA which is then hydrolyzed to 7,8,17-trihydroxy and 7,16,17-trihydorxy products, RvD1 and RvD2, respectively; and 635:: suppresses their migration to lymph nodes as well as their release of pro-inflammatory cytokines and expression of 7341:"Cyclopentenone-containing oxidized phospholipids and their isoprostanes as pro-resolving mediators of inflammation" 5233:"Systems approach to inflammation resolution: identification of novel anti-inflammatory and pro-resolving mediators" 4587:, 5,6-epoxyisoprostane E2 and 5,6-epoxyisoprostane A2. Both PGJ2's are arachidonic acid-derived metabolites made by 457: 327: 90: 3145:

of PD1 formed by the initial metabolism of DHA by aspirin-treated COX-2 or possibly a cytochrome P450 enzyme to 17

725:

system of cells thereby increasing the production of the tissue-protective gaso-transmitter, carbon monoxide (see

1657: 1156: 678: 1210:−3 DPA). All three of these omega−3 fatty acids are abundant in salt water fish, fish oils, and other seafood. 549:, a product which acts to restore mucosal integrity; Inhibits the production of the pro-inflammatory cytokines, 471:: inhibit their migration from the blood circulation into inflamed tissues and their release of tissue-injuring 7188:"Novel 14,21-dihydroxy-docosahexaenoic acids: structures, formation pathways, and enhancement of wound healing" 2708:−3 DPA-derived resolvins have not been defined with respect to the chirality of their hydroxyl residues or the 870:-lipoxins viz., 15-epi-LXA4 and 15-epi-LXB4, through a pathway that involves ALOX5 followed by aspirin-treated 558: 7290:"Decoding functional metabolomics with docosahexaenoyl ethanolamide (DHEA) identifies novel bioactive signals" 6405:

Ramon S, Baker SF, Sahler JM, Kim N, Feldsott EA, Serhan CN, Martínez-Sobrido L, Topham DJ, Phipps RP (2014).

370:

by increasing the permeability of local blood vessels; activating tissue-bound pro-inflammatory cells such as

882:-hydroperoxy-eicosatetraenoic acid whereas the ALOX15 (or ALOX15B) pathway metabolizes arachidonic acid to 15 6727:"Stereoselective Synthesis, Configurational Assignment and Biological Evaluations of the Lipid Mediator RvD2 4600: 4559: 3455:

While not yet given trivial names, certain isomers of the protectins also prove to have SPM activity: the 13

903: 794: 472: 271: 230: 2500:

respect to the SPMS, both receptors mediate the perception of various forms of inflammation-triggered pain.

1179: 790: 619:

cells: inhibit the release of pro-inflammatory cytokines by this central nervous system type of macrophage.

237: 7472:

Aslam I, Sandoval LF, Feldman SR (2014). "What's new in the topical treatment of allergic skin diseases".

6503:

Yokokura Y, Isobe Y, Matsueda S, Iwamoto R, Goto T, Yoshioka T, Urabe D, Inoue M, Arai H, Arita M (2014).

5147:"Lipoxins: novel series of biologically active compounds formed from arachidonic acid in human leukocytes" 4387:

of animal models and possesses in vitro and in vivo anti-inflammatory activity almost as potently as PD1.

2532: 1785:-hydroxy residue; however, if aspirin-treated cyclooxygenase-2 is the initiating enzyme, they contain a 17 453: 226: 2709: 7571: 4967:

Wallace JL, Ianaro A, Flannigan KL, Cirino G (2015). "Gaseous mediators in resolution of inflammation".

1203: 777:(Lx), resolvins (Rv), protectins (PD) (also termed neuroprotectins ), and maresins (MaR). EPA, DHA, and 770: 738: 566: 395: 4562:; this effect tends to reduce inflammatory reactions. PUFA-cyclopentenones may likewise react with the 3459: 248:

Through most of its early period of study, acute inflammatory responses were regarded as self-limiting

7581: 7090: 6231: 5158: 5015: 4534: 4433:) differing from the latter fatty acid only in the location of its 5 double bonds. Cells metabolize 3341: 3286: 1629: 742: 538: 406:, discovered that human neutrophils metabolize arachidonic acid to two novel products that contain 3 249: 190: 106: 1159:) is a ligand-activated transcription factor that regulates xenobiotic-metabolizing enzymes such as 7576: 4932:

Haworth O, Buckley CD (2015). "Pathways involved in the resolution of inflammatory joint disease".

3121: 1561: 1504: 1426: 682: 7497: 7454: 7031:

Serhan CN, Gotlinger K, Hong S, Lu Y, Siegelman J, Baer T, Yang R, Colgan SP, Petasis NA (2006).

7013: 6338: 6012: 5814: 5262: 4790: 4712: 3108:-hydroperoxy intermediates (see previous subsection); this intermediate is then converted to a 16 504: 391: 218: 186: 109:, primarily in animal models and human tissues, implicate SPM in orchestrating the resolution of 6505:"Identification of 14,20-dihydroxy-docosahexaenoic acid as a novel anti-inflammatory metabolite" 3749:-hydroxy metabolites of DHA. The latter hydroxy metabolites can be converted by an unidentified 6609:"Elucidation of novel 13-series resolvins that increase with atorvastatin and clear infections" 6549:"Novel proresolving and tissue-regenerative resolvin and protectin sulfido-conjugated pathways" 6220:"Resolvin D4 stereoassignment and its novel actions in host protection and bacterial clearance" 7550: 7521:"Proresolving Lipid Mediators and Mechanisms in the Resolution of Acute Inflammation (Review)" 7489: 7446: 7411: 7362: 7321: 7270: 7219: 7168: 7116: 7054: 7005: 6970: 6920: 6885: 6827: 6760: 6696: 6638: 6580: 6526: 6485: 6436: 6387: 6330: 6295: 6257: 6200: 6151: 6116: 6064: 6004: 5944: 5868: 5806: 5771: 5720: 5670: 5632: 5578: 5516: 5462: 5413: 5353: 5315: 5254: 5213: 5186: 5127: 5092: 5041: 4984: 4949: 4914: 4860: 4831:"The resolution code of acute inflammation: Novel pro-resolving lipid mediators in resolution" 4782: 4634: 4430: 3730: 3443: 3392: 3337: 3282: 3227: 1291: 399: 279: 5336:

Headland SE, Norling LV (2015). "The resolution of inflammation: Principles and challenges".

7540: 7532: 7481: 7438: 7401: 7393: 7352: 7311: 7301: 7260: 7250: 7209: 7199: 7158: 7150: 7106: 7098: 7044: 6997: 6962: 6912: 6875: 6867: 6817: 6807: 6750: 6742: 6688: 6628: 6620: 6570: 6560: 6516: 6475: 6467: 6426: 6418: 6377: 6369: 6322: 6287: 6247: 6239: 6190: 6182: 6143: 6106: 6098: 6054: 6046: 5996: 5934: 5926: 5858: 5850: 5798: 5761: 5751: 5712: 5662: 5622: 5612: 5568: 5558: 5506: 5498: 5452: 5444: 5403: 5395: 5345: 5305: 5295: 5244: 5176: 5166: 5119: 5082: 5072: 5031: 5023: 4976: 4941: 4904: 4894: 4850: 4842: 4774: 4652: 1553: 871: 562: 526: 437: 433: 403: 275: 161: 157: 4765:

Qu Q, Xuan W, Fan GH (2015). "Roles of resolvins in the resolution of acute inflammation".

4690:

in a study of 60 infants. A synthetic analog of ReV1 is in clinical phase III testing (see

625:: inhibit their infiltration into inflamed tissues and, in lung mast cells, the release of 530: 124:

SPM join the long list of other physiological agents which tend to limit inflammation (see

6218:

Winkler JW, Orr SK, Dalli J, Cheng CY, Sanger JM, Chiang N, Petasis NA, Serhan CN (2016).

5487:"Specialized pro-resolving mediators: endogenous regulators of infection and inflammation" 5286: 4647: 3754: 3750: 3133: 3129: 3086: 2663: 1698: 1633: 1267: 1160: 726: 441: 202: 149: 102: 6147: 1322:-hydroxy product, Rv3. Rv3, as detected in in vitro studies, is a dihydroxy mixture of 18 1151:

of mice; GPR32 (also termed the RvD1 receptor or DRV1)is expressed on human neutrophils,

521:

lymphocytes into inflamed sites and inhibits production of the pro-inflammatory signals,

7288:

Yang R, Fredman G, Krishnamoorthy S, Agrawal N, Irimia D, Piomelli D, Serhan CN (2011).

7094: 6235: 5162: 5019: 1664:

receptor and ion channel protein involved in controlling synaptic plasticity and memory.

7545: 7520: 7406: 7381: 7316: 7289: 7265: 7238: 7214: 7187: 7163: 7138: 7111: 7078: 6880: 6851: 6822: 6795: 6755: 6726: 6633: 6608: 6575: 6548: 6480: 6455: 6431: 6406: 6382: 6252: 6219: 6195: 6170: 6111: 6086: 6059: 6034: 5939: 5914: 5863: 5838: 5766: 5739: 5627: 5600: 5573: 5546: 5511: 5486: 5457: 5432: 5408: 5383: 5310: 5281: 5087: 5060: 5036: 5003: 4909: 4882: 4855: 4830: 4700: 4655: 4588: 4546: 2607:

worms, and to have potent anti-inflammatory activity in various in vitro model systems.

1625: 1133: 722: 632: 613:, more resistant to become apoptotic, and more active in leaving sites of inflammation. 610: 554: 550: 542: 367: 133: 129: 98: 86: 5181: 5146: 4883:"Role of docosahexaenoic acid in the modulation of glial cells in Alzheimer's disease" 7565: 7442: 6326: 5249: 5232: 5123: 4621: 4580: 3089: 2682: 2496: 702: 522: 407: 359: 351: 291: 206: 168:

clinically useful pharmacological tools for preventing and resolving a wide range of

141: 7501: 7458: 7017: 6989: 6342: 6016: 4794: 7154: 5818: 5266: 4659: 4629: 4596: 3682: 3142: 3075: 2659: 1274:

cytochrome P450 may supply this activity) or aspirin-treated cyclooxygenase-2 to 18

874:(COX-2). Aspirin-treated COX-2, while inactive in metabolizing arachidonic acid to 785:−3 fatty acids; their conversions to SPM are proposed to be one mechanism by which 636: 574: 546: 461: 257: 169: 153: 125: 118: 110: 94: 6966: 6773:

see section 'Conclusion', for other resolvins in the table see 'Figure 1' and use

689:

SPMs also stimulate anti-inflammatory and tissue reparative types of responses in

7536: 7485: 7357: 7340: 7001: 6916: 6692: 6357: 6356:

Chiang, Nan; de la Rosa, Xavier; Libreros, Stephania; Serhan, Charles N. (2017).

6000: 5854: 5839:"DHA- and EPA-derived resolvins, protectins, and maresins in airway inflammation" 5716: 5666: 5399: 2531:-docosahexaenoic acid (17-HpDHA) which may then be rapidly reduced by a cellular 1112:

The FPL2 receptor (also termed the ALX, ALX/FPR2 receptor) is expressed on human

890:(AT-lipoxins) or epi-lipoxins differ structurally from LxA4 and LxB4 only in the 811:

Human cells synthesize LxA4 and LxB4 by serially metabolizing arachidonic acid (5

7049: 7032: 5930: 5547:"Biological Roles of Resolvins and Related Substances in the Resolution of Pain" 4617: 4584: 4526: 3598: 2600: 1652:, monocytes, macrophages, and vascular tissue. TRPV1 and TRPV3 are expressed on 1148: 714: 694: 411: 331: 6456:"Specialized proresolving mediators (SPMs) inhibit human B-cell IgE production" 6291: 6186: 6102: 5349: 5151:

Proceedings of the National Academy of Sciences of the United States of America

4980: 4945: 4846: 4178:

based on their structural analogies to MaR1, MaR2, and MaR3, respectively. MaR1

4093:-diHDHA) form in inflamed tissues and in cultures of murine macrophages; the 14 278:

which are chemotactic factors formed during the activation of the host's blood

6725:

Reinertsen AF, Primdahl KG, De Matteis R, Dalli J, Hansen TV (February 2022).

5448: 5433:"Innate immunity is a key factor for the resolution of inflammation in asthma" 4899: 4530: 4522: 4477:

products and may then oxidize these products to their corresponding oxo (i.e.

4162:−3 DPA-derived maresins are presumed to be formed in mammals by metabolism of 3154: 2678: 2669:

COX-2, thereby modify this enzyme's activity. The modified enzyme metabolizes

2596: 1660:, that are involved in the sensory perception of pain; the NMDA receptor is a 1649: 1152: 1140: 1136: 1125: 1117: 1113: 875: 710: 706: 698: 690: 602: 594: 578: 510: 494: 468: 387: 379: 375: 260: 145: 7397: 7255: 7239:"Functional Metabolomics Reveals Novel Active Products in the DHA Metabolome" 6422: 6373: 5300: 1294:

to form a 5,12,18-trihydroxy derivative, RvE1. In vitro, ALOX5 can convert 18

587:: inhibit their aggregation and possibly thereby their contribution to blood 7306: 6774: 5171: 3562:

worms, and have potent anti-inflammatory activity in in vitro model systems.

1661: 1645: 1617: 1144: 898: 626: 622: 616: 598: 570: 488: 484: 476: 371: 295: 198: 7554: 7493: 7450: 7415: 7366: 7325: 7274: 7223: 7172: 7120: 7058: 7009: 6974: 6924: 6889: 6831: 6764: 6746: 6700: 6642: 6584: 6530: 6489: 6440: 6391: 6334: 6299: 6261: 6204: 6155: 6120: 6068: 6008: 5985:"n-3 Fatty acid supplementation and proresolving mediators of inflammation" 5948: 5872: 5810: 5775: 5724: 5674: 5636: 5582: 5520: 5466: 5417: 5357: 5319: 5258: 5096: 5061:"The resolution of inflammation: the devil in the flask and in the details" 5045: 4988: 4953: 4918: 4864: 4786: 4509:(17-EFOX-D3). These oxo metabolites directly activate the nuclear receptor 1930:

Anti-inflammatory, blocks pain perception, increases survival after sepsis

497:: inhibit their migration from the blood circulation into inflamed tissues. 7345:

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids

6812: 6471: 6171:"Resolution phase lipid mediators of inflammation: agonists of resolution" 5655:

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids

5563: 5388:

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids

5217: 5190: 5131: 5077: 4521:

DHA ethanolamide ester (the DHA analog of arachindonyl ethanolamide (i.e.

4101:,21-diHDHA isomers promoted wound healing in mouse models of inflammation. 3153:-hydroxy diastereomer of PD1, has been detected in small amounts in human 378:; and attracting to nascent inflammatory sites and activating circulating 7137:

Hong S, Lu Y, Tian H, Alapure BV, Wang Q, Bunnell BA, Laborde JM (2014).

6565: 3559: 3273: 2723: 2643: 2604: 1797: 1358: 1271: 1173: 1121: 718: 606: 588: 584: 573:

in the neutrophils and eosinophil of inflamed tissues; and increases the

500: 449: 419: 383: 287: 222: 214: 182: 174: 114: 7204: 6521: 6504: 6087:"Emerging roles of resolvins in the resolution of inflammation and pain" 5027: 4513:

and possess anti-inflammatory activity as assesses in in vitro systems.

3218:

anti-inflammatory, nerve protection/regeneration, blocks pain perception

5756: 5502: 4778: 4695: 4575: 4571: 4384: 3694: 3667: 3117: 2688: 2677:-hydroperoxy-n−3 DPA intermediate which is passed over to nearby human 2647: 1637: 1621: 1214:−3 DPA (also termed clupanodonic acid) is to be distinguished from its 855: 835: 806: 774: 445: 415: 347: 7102: 6871: 6243: 5802: 5617: 537:

lymphocytes to differentiate into antibody secreting cells; inhibits

6050: 5204:

Watoh Y, Hirosawa J, Saitoh N, Oda M, Sato T, Yamauchi N (1989). "".

4699:

loss. And, in a single study, inhaled LXA4 decreased LTC4-initiated

4687: 4639: 4613: 4554: 4478: 4422: 3778: 3774: 3770: 3766: 3762: 3758: 3678: 3125: 3097: 3093: 2716: 2655: 1653: 1557: 1500: 1422: 1129: 911:

15-Hydroxyeicosatetraenoic acid § Nomenclature and stereoisomers

863: 851: 831: 642: 534: 343: 323: 210: 178: 6624: 6454:

Kim N, Ramon S, Thatcher TH, Woeller CF, Sime PJ, Phipps RP (2016).

3452:

The TRPV1 receptor is discussed in the EPA-derived resolvin section.

5004:"Pro-resolving lipid mediators are leads for resolution physiology" 3757:; alternatively, DHA may be first metabolized to 22-hydroxy-DHA by 3085:

Cells metabolize DHA by either ALOX15, by a bacterial or mammalian

2599:, detected in the peritoneal fluid of mice undergoing experimental 518: 514: 4592: 4550: 4470: 4462: 3848: 3844: 3685:, (12/15-lipoxygenase in mice), or an unidentified pathway to a 13 3222: 2651: 2332: 2217: 2213: 2209: 2098: 2003: 1950: 1946: 1938: 1934: 1881: 1877: 1873: 1865: 1442: 1438: 1434: 839: 674: 670: 662: 658: 654: 650: 319: 299: 4567: 4563: 3128:. 22-Hydroxy-PD1 (also termed 22-hydroxy-NPD1) is formed by the 2692:

bacteria. Another set of newly described n−3 DPA resolvins, RvD1

2221: 2205: 1942: 1869: 1641: 1446: 1061: 970: 666: 480: 335: 315: 311: 307: 303: 4646:

Concurrent knockout of the three members of the CYP1 family of

3729:-epoxy-maresin MaR) and then hydrolyze this intermediate by an 4104:

Mouse eosinophils metabolize DHA to a maresin-like product, 14

3840:

anti-inflammatory, tissue regeneration, blocks pain perception

2686:

increasing the survival of mice injected with lethal doses of

1565: 1508: 1430: 974: 18: 4881:

Heras-Sandoval D, Pedraza-Chaverri J, Pérez-Rojas JM (2016).

6358:"Novel Resolvin D2 Receptor Axis in Infectious Inflammation" 2681:; these cells then metabolize the intermediate to four poly- 1636:

and in brain, kidney, cardiovascular, gastrointestinal, and

6988:

Lagarde M, Véricel E, Liu M, Chen P, Guichardant M (2014).

5382:

Serhan CN, Dalli J, Colas RA, Winkler JW, Chiang N (2015).

4144:

isomer possesses potent anti-inflammatory activity in mice.

475:

and granule-bound enzymes; stimulates their expression the

2503:

The initial product of 15-lipoxygenase attack on DHA is 17

605:) that are more active in secreting the anti-inflammatory 140:(an inhibitor of the action of pro-inflammatory cytokine, 6547:

Dalli J, Ramon S, Norris PC, Colas RA, Serhan CN (2015).

6033:

Oh SF, Pillai PS, Recchiuti A, Yang R, Serhan CN (2011).

789:−3 fatty acids may ameliorate inflammatory diseases (see 685:, and/or spinal cord thereby suppressing pain perception. 3782:

activities and cellular receptor targets (where known).

4682:, AT-LXA4 and a comparatively stable analog of LXB4, 15 4136:-docosahexaenoic acid. This product, as well as its 14, 3092:(Cyp1a1, Cyp1a2, or Cyp1b1 in mice; see CYP450 §§ 418:

A4 and B4, respectively. While initially found to have

39: 4658:

level and decreases in the levels of peritoneal fluid

156:), and hydrogen sulfide (see Hydrogen sulfide §§ 6796:"Roles of Resolvins in Chronic Inflammatory Response" 1709:-hydroxy-DHA. ALOX5 metabolizes this intermediate to 7079:"Novel n-3 immunoresolvents: structures and actions" 4662:

as well as the precursors to various SPMs including

773:

or clupanodonic acid); these metabolites are termed

5915:"Lipid mediators in the resolution of inflammation" 5112:

Biochemical and Biophysical Research Communications

4583:, (PG) Δ12-PGJ2 and 15-deoxy-Δ12,14-PGJ2, and two 3597:has anti-inflammatory activity in a mouse model of 846:ALOX5 followed by ALOX15 (or possibly ALOX15B); or 34:

may be too technical for most readers to understand

7474:Current Opinion in Allergy and Clinical Immunology 6852:"GPR101 mediates the pro-resolving actions of RvD5 3843:Inhibits the activation of the vanilloid receptor 2156: 1282:-hydroxy-EPA and further metabolized by ALOX5 to 5 541:from releasing pro-inflammatory cytokines such as 6794:Liu C, Fan D, Lei Q, Lu A, He X (December 2022). 1314:-HETE may also be metabolized by ALOX15 to its 17 1238:-docosapentaenoic acid, also termed osbond acid. 483:, to inhibit chemokine signaling, enhances their 16:Cellular molecules that help resolve inflammation 6674: 6672: 5978: 5908: 5906: 5904: 5902: 5740:"Lipoxins: nature's way to resolve inflammation" 4511:peroxisome proliferator-activated receptor gamma 3753:enzyme to maresin like-1 (Mar-L1) and Mar-L2 by 7519:Buckley CD, Gilroy DW, Serhan CN (March 2014). 7132: 7130: 7072: 7070: 7068: 6948: 6946: 6944: 6942: 6940: 6938: 6936: 6934: 6670: 6668: 6666: 6664: 6662: 6660: 6658: 6656: 6654: 6652: 6602: 6600: 6598: 6596: 6594: 6542: 6540: 6273: 6271: 6080: 6078: 6028: 6026: 5976: 5974: 5972: 5970: 5968: 5966: 5964: 5962: 5960: 5958: 5900: 5898: 5896: 5894: 5892: 5890: 5888: 5886: 5884: 5882: 5832: 5830: 5828: 5698: 5696: 5694: 5692: 5690: 5688: 5686: 5684: 5648: 5646: 5594: 5592: 5540: 5538: 5536: 5534: 5532: 5530: 5480: 5478: 5476: 5377: 5375: 5373: 5371: 5369: 5367: 5331: 5329: 4824: 4760: 4758: 4756: 4754: 4752: 4750: 4748: 529:by CD4+ lymphocytes; promotes the apoptosis of 366:). These agents functioned as pro-inflammatory 330:, and PUFA metabolites including in particular 89:molecules formed in cells by the metabolism of 6085:Ji RR, Xu ZZ, Strichartz G, Serhan CN (2011). 5913:Serhan CN, Chiang N, Dalli J, Levy BD (2015). 4876: 4874: 4822: 4820: 4818: 4816: 4814: 4812: 4810: 4808: 4806: 4804: 4746: 4744: 4742: 4740: 4738: 4736: 4734: 4732: 4730: 4728: 4694:) for the treatment of the inflammation-based 3393:Neuroprotectin D1 § Aspirin-triggered PD1 3100:) or by aspirin-treated cyclooxygenase-2 to 17 737:SPM are metabolites of arachidonic acid (AA), 282:by invading organisms or injured tissues; and 6720: 6718: 6716: 6714: 6712: 6710: 5206:Masui. The Japanese Journal of Anesthesiology 4505:-D5), 17-oxo-DHA (17-EFOX-D6), and 17-oxo-DPA 4421:-docosapentaenoic acid or osbond acid) is an 4328:Other PUFA metabolites with SPM-like activity 1697:-docosahexaenoic acid) by either ALOX15 or a 8: 1278:-hydroperoxy-EPA which is then reduced to 18 886:-hydroperoxy-eicosatetraenoic acid. The two 6800:International Journal of Molecular Sciences 5738:Chandrasekharan JA, Sharma-Walia N (2015). 5145:Serhan CN, Hamberg M, Samuelsson B (1984). 1721:-hydroxy-DHA which is then reduced to its 7 7237:Shinohara M, Mirakaj V, Serhan CN (2012). 6136:Prostaglandins & Other Lipid Mediators 5919:Cold Spring Harbor Perspectives in Biology 601:to an anti-inflammatory M2 phenotype (see 507:and release of pro-inflammatory mediators. 7544: 7405: 7356: 7315: 7305: 7264: 7254: 7213: 7203: 7162: 7110: 7048: 6879: 6821: 6811: 6754: 6632: 6574: 6564: 6520: 6479: 6430: 6381: 6251: 6194: 6110: 6058: 5938: 5862: 5765: 5755: 5626: 5616: 5605:Journal of Atherosclerosis and Thrombosis 5572: 5562: 5510: 5456: 5407: 5309: 5299: 5248: 5180: 5170: 5086: 5076: 5035: 4908: 4898: 4854: 3570:−3 DPA-derived protectins/neuroprotectins 2201:Anti-inflammatory, blocks pain perception 1861:Anti-inflammatory, blocks pain perception 1656:and supporting cells, principally of the 1496:Anti-inflammatory, blocks pain perception 1418:Anti-inflammatory, blocks pain perception 1102:Anti-inflammatory, blocks pain perception 1057:Anti-inflammatory, blocks pain perception 1015:Anti-inflammatory, blocks pain perception 966:Anti-inflammatory, blocks pain perception 854:. Cells and, indeed, humans treated with 62:Learn how and when to remove this message 46:, without removing the technical details. 4517:Docosahexaenoyl ethanolamide metabolites 4189: 3784: 3608: 3159: 3120:which is then hydrolyzed (probably by a 2727: 1801: 1362: 1270:monooxygenase(s) (in infected tissues a 914: 557:, thereby contributing to the dampening 154:Nitric oxide § Biological functions 6845: 6843: 6841: 4724: 4481:) derivatives, 13-oxo-DHA (also termed 1705:-hydroperoxy-DHA which is reduced to 17 1318:-hydroperoxy and then reduced to its 17 533:pro-inflammatory lymphocytes; promotes 265:N-formylmethionine-leucyl-phenylalanine 6789: 6787: 6785: 6783: 4686:-methyl-LXB4, reduced the severity of 3081:DHA-derived protectins/neuroprotectins 1741:-hydroxy-DHA which is reduced to its 4 791:Omega−3 fatty acid § Inflammation 503:: inhibit their migration response to 487:activity, and promotes their death by 256:foreign organism-derived N-formylated 7077:Dalli J, Colas RA, Serhan CN (2013). 6607:Dalli J, Chiang N, Serhan CN (2015). 6039:The Journal of Clinical Investigation 5237:Journal of Thrombosis and Haemostasis 4829:Serhan CN, Chiang N, Dalli J (2015). 4033:Studies in mice detected a series of 3338:Neuroprotectin D1 § Protectin DX 3283:Neuroprotectin D1 § Protectin DX 44:make it understandable to non-experts 7: 6148:10.1016/j.prostaglandins.2012.01.005 5280:Hansen TV, Vik A, Serhan CN (2019). 4473:to 17-hydroxy-DHA and 17-hydroxy-DPA 4465:to 13-hydroxy-DHA and 13-hydroxy-DPA 7294:The Journal of Biological Chemistry 4574:protein complex thereby inhibiting 3444:Neuroprotectin D1 § 10-epi-PD1 3132:of PD1 probably by an unidentified 286:host cell-derived pro-inflammatory 236:Many of the SPM are metabolites of 85:) are a large and growing class of 75:Specialized pro-resolving mediators 7431:The British Journal of Dermatology 5983:Barden AE, Mas E, Mori TA (2016). 5545:Lim JY, Park CK, Hwang SW (2015). 2724:Resolvin § T series resolvins 1789:-hydroxy residue and are termed 17 545:while stimulating them to secrete 93:(PUFA) by one or a combination of 83:specialized proresolving mediators 14: 6860:Journal of Clinical Investigation 4616:injury, airway inflammation, and 4497:erivative or EFOX-D6), 13-oxo-DPA 4061:-docosahexaenoic acid isomers (14 3741:isomer of Mar1, as well as the 14 3649:16,17-dihydroxy-7,10,12,14,19-DPA 3632:10,17-dihydroxy-7,11,13,15,19-DPA 1640:tissues; BLT is the receptor for 1346:-hydroxy analog of RvE2 termed 18 727:Carbon monoxide § Physiology 294:), host-derived pro-inflammatory 150:Carbon monoxide § Physiology 138:interleukin 1 receptor antagonist 136:(an anti-inflammatory cytokine), 7443:10.1111/j.1365-2133.2012.11177.x 6850:Flak, M.B.; et al. (2022). 6681:European Journal of Pharmacology 6327:10.1016/j.neuropharm.2014.05.043 5843:European Journal of Pharmacology 5744:Journal of Inflammation Research 5705:European Journal of Pharmacology 5250:10.1111/j.1538-7836.2009.03396.x 4469:products and by aspirin-treated 649:to inhibit pain receptors (i.e. 113:. Prominent members include the 23: 6175:Current Opinion in Pharmacology 5599:Shinohara M, Serhan CN (2016). 4668:15-hydroxyeicosatetraenoic acid 4541:Prostaglandins and isoprostanes 4453:Oxo-DHA and oxo-DPA metabolites 7339:Friedli O, Freigang S (2016). 7155:10.1016/j.chembiol.2014.06.010 6735:Chemistry - A European Journal 6460:European Journal of Immunology 4664:5-hydroxyeicosatetraenoic acid 4545:PUFA derivatives containing a 513:: Inhibit the infiltration of 126:Inflammation § Resolution 1: 7186:Lu Y, Tian H, Hong S (2010). 6967:10.1016/j.plipres.2015.10.002 5989:Current Opinion in Lipidology 5551:BioMed Research International 4383:) has been found in inflamed 1266:-eicosapentaenoic acid) by a 1178:Resolvins are metabolites of 878:, metabolizes this PUFA to 15 827:-eicosatetraenoic acid) with 462:Inflammation § Disorders 340:hydroxyeicosatetraenoic acids 7537:10.1016/j.immuni.2014.02.009 7486:10.1097/ACI.0000000000000093 7358:10.1016/j.bbalip.2016.07.006 7002:10.1016/j.biochi.2014.09.008 6917:10.1016/j.biochi.2013.11.006 6856:in arthritis and infections" 6693:10.1016/j.ejphar.2015.11.002 6169:Serhan CN, Chiang N (2013). 6001:10.1097/MOL.0000000000000262 5855:10.1016/j.ejphar.2015.11.001 5717:10.1016/j.ejphar.2015.03.083 5667:10.1016/j.bbalip.2014.08.010 5400:10.1016/j.bbalip.2014.08.006 5124:10.1016/0006-291x(84)91486-4 4887:Journal of Neuroinflammation 3272:anti-inflammatory, inhibits 1139:, and intestinal and airway 195:systemic lupus erythematosus 7050:10.4049/jimmunol.176.3.1848 6280:Current Medicinal Chemistry 5931:10.1101/cshperspect.a016311 5837:Duvall MG, Levy BD (2015). 5437:European Respiratory Review 4692:Phases of clinical research 4680:randomized controlled trial 4626:respiratory syncytial virus 4566:component of the cytosolic 3221:inhibits the activation of 1798:Resolvin § Resolvin Ds 1359:Resolvin § Resolvin Es 647:G protein–coupled receptors 645:: act through their target 91:polyunsaturated fatty acids 7598: 6955:Progress in Lipid Research 6292:10.2174/092986712798918851 6187:10.1016/j.coph.2013.05.012 6103:10.1016/j.tins.2011.08.005 5491:Nature Reviews. Immunology 5485:Basil MC, Levy BD (2016). 5431:Barnig C, Levy BD (2015). 5350:10.1016/j.smim.2015.03.014 4981:10.1016/j.smim.2015.05.004 4946:10.1016/j.smim.2015.04.002 4847:10.1016/j.smim.2015.03.004 4767:Cell Biology International 4371:-docosapentaenoic acid (10 3665: 3073: 3070:Protectins/neuroprotectins 2721: 1795: 1356: 1342:-hydroperoxy-EPA to the 18 1171: 908: 888:aspirin-triggered lipoxins 804: 603:Macrophage § Subtypes 458:inflammatory bowel disease 328:platelet-activating factor 7192:Journal of Lipid Research 6362:The Journal of Immunology 5449:10.1183/09059180.00012514 5287:Frontiers in Pharmacology 4900:10.1186/s12974-016-0525-7 4703:in patients with asthma. 4607:Gene manipulation studies 4457:Cells metabolize DHA and 3122:soluble epoxide hydrolase 2212:, inhibits activation of 1945:, inhibits activation of 1872:, inhibits activation of 1749:-dihydroxy analog, RvD6; 1729:-dihydroxy analog, RvD5; 1658:peripheral nervous system 1433:, inhibits activation of 1157:aryl hydrocarbon receptor 679:peripheral nervous system 559:adaptive immune responses 272:complement components C5a 7398:10.4049/jimmunol.1300699 7256:10.3389/fimmu.2012.00081 6423:10.4049/jimmunol.1302795 6374:10.4049/jimmunol.1601650 5301:10.3389/fphar.2018.01582 4445:, and 7,17-dihydroxy-DPA 3677:Cells metabolize DHA by 3399:10-epi-PD1 (ent-AT-NPD1) 2615:−3 DPA-derived resolvins 1302:analog of RvE1 termed 18 1068:15-epi-LxB4 (or AT-LxB4) 1023:15-epi-LxA4 (or AT-LxA4) 866:lipoxins of these two 15 729:), in inflamed tissues. 721:as well as activate the 354:heptadecatrienoic acid, 7307:10.1074/jbc.M111.237990 7243:Frontiers in Immunology 7143:Chemistry & Biology 6777:(RvT3 is not depicted). 6769:For the formula of RvD2 6509:Journal of Biochemistry 6091:Trends in Neurosciences 5791:Pharmacological Reviews 5172:10.1073/pnas.81.17.5335 4601:reactive oxygen species 4560:reactive oxygen species 4553:component of the KEAP1- 4437:−6 DPA to 7-hydroxy-DPA 4155:−3 DPA-derived maresins 1673:Cells metabolize DHA (4 1246:Cells metabolize EPA (5 473:reactive oxygen species 105:monooxygenase enzymes. 6747:10.1002/chem.202103857 5338:Seminars in Immunology 4969:Seminars in Immunology 4934:Seminars in Immunology 4835:Seminars in Immunology 3098:P450s in other species 3094:CYP families in humans 2533:glutathione peroxidase 1054:-eicosatetraenoic acid 569:lymphocytes to induce 396:natural killer T cells 7386:Journal of Immunology 7037:Journal of Immunology 6813:10.3390/ijms232314883 6472:10.1002/eji.201545673 6411:Journal of Immunology 5078:10.1096/fj.11-0502ufm 4441:, 10,17-dihydroxy-DPA 3721:-DHA intermediate (13 1669:DHA-derived resolvins 1630:innate lymphoid cells 1242:EPA-derived resolvins 1218:−6 DPA isomer, i.e. 4 1204:docosapentaenoic acid 771:docosapentaenoic acid 739:eicosapentaenoic acid 567:natural killer T cell 539:innate lymphoid cells 152:), nitric oxide (see 6566:10.1096/fj.14-268441 4535:cannabinoid receptor 3673:DHA-derived maresins 3342:Dihydroxy-E,Z,E-PUFA 3287:Dihydroxy-E,Z,E-PUFA 3175:See Knowledge pages 1099:-eicosatrienoic acid 743:docosahexaenoic acid 677:) on neurons in the 581:in inflamed tissues. 250:innate immune system 231:Huntington's disease 213:, type 1 and type 2 191:rheumatoid arthritis 107:Pre-clinical studies 7205:10.1194/jlr.M000059 7095:2013NatSR...3E1940D 6236:2016NatSR...618972W 5564:10.1155/2015/830930 5163:1984PNAS...81.5335S 5028:10.1038/nature13479 5020:2014Natur.510...92S 3348:17-epi-PD1 (AT-PD1) 2710:cis−trans isomerism 2650:to form acetylated 1562:receptor antagonist 1505:receptor antagonist 1427:receptor antagonist 1334:-dihydroxy (i.e. 18 1326:-dihydroxy (i.e. 18 1180:omega−3 fatty acids 683:dorsal root ganglia 505:chemotactic factors 454:Alzheimer's disease 402:, Mats Hamberg and 392:gamma delta T cells 261:chemotactic factors 238:omega−3 fatty acids 227:Alzheimer's disease 205:disease leading to 187:autoimmune diseases 7083:Scientific Reports 6996:. 107 Pt A: 91–4. 6224:Scientific Reports 5757:10.2147/JIR.S90380 5503:10.1038/nri.2015.4 5231:Serhan CN (2009). 5059:Serhan CN (2011). 5002:Serhan CN (2014). 4779:10.1002/cbin.10345 4713:N-Acylethanolamine 4701:bronchoprovocation 4394:−6-DPA metabolites 4339:−3 DPA metabolites 3104:-hydroperoxy or 17 850:ALOX5 followed by 795:cellular receptors 219:metabolic syndrome 7103:10.1038/srep01940 6872:10.1172/JCI131609 6741:(7): e202103857. 6522:10.1093/jb/mvu044 6315:Neuropharmacology 6244:10.1038/srep18972 5803:10.1124/pr.58.3.4 5618:10.5551/jat.33928 5243:(Suppl 1): 44–8. 4635:Toxoplasma gondii 4529:tissue and human 4431:clupanodonic acid 4325: 4324: 4295:14,21-dihydroxy-7 4281:anti-inflammatory 4258:13,14-dihydroxy-7 4244:anti-inflammatory 4097:,21-diHDHA and 14 4037:14,21-dihydroxy-4 4030: 4029: 4023:anti-inflammatory 3981:anti-inflammatory 3939:anti-inflammatory 3893:anti-inflammatory 3731:epoxide hydrolase 3659: 3658: 3652:anti-inflammatory 3635:anti-inflammatory 3462:of 10-epi-PD1, 10 3449: 3448: 3437:anti-inflammatory 3386:anti-inflammatory 3331:anti-inflammatory 3228:Neuroprotectin D1 3067: 3066: 3060:Anti-inflammatory 3015:Anti-inflammatory 2966:Anti-inflammatory 2917:Anti-inflammatory 2875:Anti-inflammatory 2829:Anti-inflammatory 2783:Anti-inflammatory 2492: 2491: 2328:Anti-inflammatory 2094:Anti-inflammatory 2021:,17S-trihydroxy-6 1999:Anti-inflammatory 1613: 1612: 1606:Anti-inflammatory 1549:Anti-inflammatory 1292:epoxide hydrolase 1182:, EPA, DHA, and 7 1109: 1108: 563:T helper 17 cells 400:Charles N. Serhan 280:complement system 72: 71: 64: 7589: 7558: 7548: 7506: 7505: 7469: 7463: 7462: 7426: 7420: 7419: 7409: 7377: 7371: 7370: 7360: 7336: 7330: 7329: 7319: 7309: 7300:(36): 31532–41. 7285: 7279: 7278: 7268: 7258: 7234: 7228: 7227: 7217: 7207: 7183: 7177: 7176: 7166: 7134: 7125: 7124: 7114: 7074: 7063: 7062: 7052: 7028: 7022: 7021: 6985: 6979: 6978: 6950: 6929: 6928: 6900: 6894: 6893: 6883: 6847: 6836: 6835: 6825: 6815: 6791: 6778: 6768: 6758: 6722: 6705: 6704: 6676: 6647: 6646: 6636: 6604: 6589: 6588: 6578: 6568: 6544: 6535: 6534: 6524: 6500: 6494: 6493: 6483: 6451: 6445: 6444: 6434: 6402: 6396: 6395: 6385: 6353: 6347: 6346: 6310: 6304: 6303: 6275: 6266: 6265: 6255: 6215: 6209: 6208: 6198: 6166: 6160: 6159: 6131: 6125: 6124: 6114: 6082: 6073: 6072: 6062: 6051:10.1172/JCI42545 6030: 6021: 6020: 5980: 5953: 5952: 5942: 5910: 5877: 5876: 5866: 5834: 5823: 5822: 5786: 5780: 5779: 5769: 5759: 5735: 5729: 5728: 5700: 5679: 5678: 5650: 5641: 5640: 5630: 5620: 5596: 5587: 5586: 5576: 5566: 5542: 5525: 5524: 5514: 5482: 5471: 5470: 5460: 5428: 5422: 5421: 5411: 5379: 5362: 5361: 5333: 5324: 5323: 5313: 5303: 5277: 5271: 5270: 5252: 5228: 5222: 5221: 5201: 5195: 5194: 5184: 5174: 5142: 5136: 5135: 5107: 5101: 5100: 5090: 5080: 5056: 5050: 5049: 5039: 5014:(7503): 92–101. 4999: 4993: 4992: 4964: 4958: 4957: 4929: 4923: 4922: 4912: 4902: 4878: 4869: 4868: 4858: 4826: 4799: 4798: 4762: 4674:Clinical studies 4653:peritoneal fluid 4190: 3785: 3609: 3460:cis–trans isomer 3304:,22-trihydroxy-4 3160: 2728: 2646:pretreated with 2158: 1802: 1634:epithelial cells 1554:receptor agonist 1363: 915: 872:cyclooxygenase-2 527:interferon gamma 438:prostaglandin D2 434:prostaglandin E2 404:Bengt Samuelsson 225:syndromes (e.g. 67: 60: 56: 53: 47: 27: 26: 19: 7597: 7596: 7592: 7591: 7590: 7588: 7587: 7586: 7562: 7561: 7518: 7515: 7510: 7509: 7471: 7470: 7466: 7428: 7427: 7423: 7379: 7378: 7374: 7338: 7337: 7333: 7287: 7286: 7282: 7236: 7235: 7231: 7185: 7184: 7180: 7149:(10): 1318–29. 7136: 7135: 7128: 7076: 7075: 7066: 7030: 7029: 7025: 6987: 6986: 6982: 6952: 6951: 6932: 6902: 6901: 6897: 6855: 6849: 6848: 6839: 6806:(23). Table 1. 6793: 6792: 6781: 6772: 6730: 6724: 6723: 6708: 6678: 6677: 6650: 6625:10.1038/nm.3911 6613:Nature Medicine 6606: 6605: 6592: 6546: 6545: 6538: 6502: 6501: 6497: 6453: 6452: 6448: 6417:(12): 6031–40. 6404: 6403: 6399: 6355: 6354: 6350: 6312: 6311: 6307: 6277: 6276: 6269: 6217: 6216: 6212: 6168: 6167: 6163: 6133: 6132: 6128: 6097:(11): 599–609. 6084: 6083: 6076: 6032: 6031: 6024: 5982: 5981: 5956: 5912: 5911: 5880: 5836: 5835: 5826: 5788: 5787: 5783: 5737: 5736: 5732: 5702: 5701: 5682: 5652: 5651: 5644: 5598: 5597: 5590: 5544: 5543: 5528: 5484: 5483: 5474: 5443:(135): 141–53. 5430: 5429: 5425: 5381: 5380: 5365: 5335: 5334: 5327: 5279: 5278: 5274: 5230: 5229: 5225: 5208:(in Japanese). 5203: 5202: 5198: 5144: 5143: 5139: 5109: 5108: 5104: 5058: 5057: 5053: 5001: 5000: 4996: 4966: 4965: 4961: 4931: 4930: 4926: 4880: 4879: 4872: 4828: 4827: 4802: 4764: 4763: 4726: 4721: 4709: 4676: 4648:cytochrome P450 4609: 4589:cyclooxygenases 4543: 4519: 4508: 4500: 4476: 4468: 4455: 4448: 4444: 4440: 4396: 4382: 4341: 4330: 4292: 4255: 4210: 4185: 4181: 4177: 4173: 4169: 4157: 4085:-diHDHA, and 14 3996:,22-dihydroxy-4 3954:,22-dihydroxy-4 3755:omega oxidation 3751:cytochrome P450 3745:-hydroxy and 14 3675: 3670: 3664: 3646: 3629: 3604: 3596: 3592: 3588: 3584: 3580: 3572: 3134:cytochrome P450 3130:omega oxidation 3087:cytochrome P450 3083: 3078: 3072: 3026: 2977: 2928: 2726: 2703: 2699: 2695: 2617: 2447:-RvD6 (AT-RvD6) 2397:-RvD5 (AT-RvD5) 2343:-RvD4 (AT-RvD4) 2286:-RvD3 (AT-RvD3) 2232:-RvD2 (AT-RvD2) 1800: 1737:-hydroperoxy,17 1717:-hydroperoxy,17 1699:cytochrome P450 1671: 1626:dendritic cells 1624:, macrophages, 1361: 1298:-HETE to the 18 1286:-hydroperoxy-18 1268:cytochrome P450 1244: 1176: 1170: 1161:cytochrome P450 913: 809: 803: 735: 633:Dendritic cells 442:atherosclerosis 429: 410:residues and 4 246: 203:atherosclerosis 162:Signalling role 130:glucocorticoids 103:cytochrome P450 68: 57: 51: 48: 40:help improve it 37: 28: 24: 17: 12: 11: 5: 7595: 7593: 7585: 7584: 7579: 7574: 7564: 7563: 7560: 7559: 7531:(3): 315–327. 7514: 7513:External links 7511: 7508: 7507: 7464: 7421: 7392:(6): 3347–57. 7372: 7351:(4): 382–392. 7331: 7280: 7229: 7178: 7126: 7064: 7043:(3): 1848–59. 7023: 6980: 6930: 6895: 6866:(1): 359–373. 6853: 6837: 6779: 6770: 6728: 6706: 6648: 6590: 6559:(5): 2120–36. 6536: 6495: 6446: 6397: 6368:(2): 842–851. 6348: 6305: 6267: 6210: 6161: 6142:(3–4): 73–82. 6126: 6074: 6022: 5954: 5925:(2): a016311. 5878: 5824: 5781: 5730: 5680: 5642: 5588: 5526: 5472: 5423: 5394:(4): 397–413. 5363: 5325: 5272: 5223: 5212:(11): 1514–7. 5196: 5157:(17): 5335–9. 5137: 5102: 5051: 4994: 4959: 4924: 4870: 4800: 4723: 4722: 4720: 4717: 4716: 4715: 4708: 4705: 4675: 4672: 4608: 4605: 4581:prostaglandins 4547:cyclopentenone 4542: 4539: 4518: 4515: 4506: 4498: 4474: 4466: 4454: 4451: 4446: 4442: 4438: 4401:−6 DPA (i.e. 4 4395: 4389: 4380: 4340: 4334: 4329: 4326: 4323: 4322: 4319: 4316: 4293: 4290: 4286: 4285: 4282: 4279: 4256: 4253: 4249: 4248: 4245: 4242: 4211: 4208: 4204: 4203: 4200: 4197: 4194: 4183: 4179: 4175: 4171: 4167: 4156: 4150: 4149: 4148: 4145: 4102: 4028: 4027: 4024: 4021: 3990: 3986: 3985: 3982: 3979: 3948: 3944: 3943: 3940: 3937: 3902: 3898: 3897: 3894: 3891: 3856: 3852: 3851: 3841: 3838: 3803: 3799: 3798: 3795: 3792: 3789: 3674: 3671: 3666:Main article: 3663: 3660: 3657: 3656: 3653: 3650: 3647: 3644: 3640: 3639: 3636: 3633: 3630: 3627: 3623: 3622: 3619: 3616: 3613: 3602: 3594: 3590: 3586: 3582: 3578: 3571: 3565: 3564: 3563: 3453: 3447: 3446: 3441: 3438: 3435: 3400: 3396: 3395: 3390: 3387: 3384: 3349: 3345: 3344: 3335: 3332: 3329: 3294: 3293:22-hydroxy-PD1 3290: 3289: 3280: 3277: 3270: 3235: 3231: 3230: 3225: 3219: 3216: 3181: 3177: 3176: 3173: 3170: 3167: 3164: 3082: 3079: 3074:Main article: 3071: 3068: 3065: 3064: 3061: 3058: 3027: 3024: 3020: 3019: 3016: 3013: 2978: 2975: 2971: 2970: 2967: 2964: 2929: 2926: 2922: 2921: 2918: 2915: 2884: 2880: 2879: 2876: 2873: 2838: 2834: 2833: 2830: 2827: 2792: 2788: 2787: 2784: 2781: 2746: 2742: 2741: 2738: 2735: 2732: 2701: 2697: 2693: 2673:−3 DPA to a 13 2622:−3 DPA (i.e. 7 2616: 2610: 2609: 2608: 2507:-hydroperoxy-4 2501: 2490: 2489: 2486: 2483: 2448: 2440: 2439: 2436: 2433: 2398: 2390: 2389: 2386: 2383: 2344: 2336: 2335: 2329: 2326: 2287: 2279: 2278: 2275: 2272: 2233: 2225: 2224: 2202: 2199: 2160: 2148: 2147: 2144: 2141: 2106: 2102: 2101: 2095: 2092: 2057: 2053: 2052: 2049: 2046: 2011: 2007: 2006: 2000: 1997: 1958: 1954: 1953: 1931: 1928: 1889: 1885: 1884: 1862: 1859: 1820: 1816: 1815: 1812: 1809: 1806: 1670: 1667: 1666: 1665: 1632:as well as on 1611: 1610: 1607: 1604: 1573: 1569: 1568: 1550: 1547: 1516: 1512: 1511: 1497: 1494: 1459: 1451: 1450: 1419: 1416: 1381: 1377: 1376: 1373: 1370: 1367: 1243: 1240: 1172:Main article: 1169: 1166: 1165: 1164: 1143:as well as on 1107: 1106: 1103: 1100: 1069: 1065: 1064: 1058: 1055: 1024: 1020: 1019: 1016: 1013: 982: 978: 977: 967: 964: 933: 929: 928: 925: 922: 919: 838:) followed by 805:Main article: 802: 799: 749:−3 DPA (i.e. 7 734: 731: 723:heme oxygenase 687: 686: 640: 630: 620: 614: 611:Interleukin-10 592: 582: 555:interleukin-23 551:interleukin-17 543:interleukin-13 508: 498: 492: 428: 425: 360:oxoeicosanoids 292:interleukin 1s 245: 242: 221:, and certain 134:interleukin 10 99:cyclooxygenase 87:cell signaling 81:, also termed 70: 69: 31: 29: 22: 15: 13: 10: 9: 6: 4: 3: 2: 7594: 7583: 7580: 7578: 7575: 7573: 7570: 7569: 7567: 7556: 7552: 7547: 7542: 7538: 7534: 7530: 7526: 7522: 7517: 7516: 7512: 7503: 7499: 7495: 7491: 7487: 7483: 7480:(5): 436–50. 7479: 7475: 7468: 7465: 7460: 7456: 7452: 7448: 7444: 7440: 7436: 7432: 7425: 7422: 7417: 7413: 7408: 7403: 7399: 7395: 7391: 7387: 7383: 7376: 7373: 7368: 7364: 7359: 7354: 7350: 7346: 7342: 7335: 7332: 7327: 7323: 7318: 7313: 7308: 7303: 7299: 7295: 7291: 7284: 7281: 7276: 7272: 7267: 7262: 7257: 7252: 7248: 7244: 7240: 7233: 7230: 7225: 7221: 7216: 7211: 7206: 7201: 7198:(5): 923–32. 7197: 7193: 7189: 7182: 7179: 7174: 7170: 7165: 7160: 7156: 7152: 7148: 7144: 7140: 7133: 7131: 7127: 7122: 7118: 7113: 7108: 7104: 7100: 7096: 7092: 7088: 7084: 7080: 7073: 7071: 7069: 7065: 7060: 7056: 7051: 7046: 7042: 7038: 7034: 7027: 7024: 7019: 7015: 7011: 7007: 7003: 6999: 6995: 6991: 6984: 6981: 6976: 6972: 6968: 6964: 6960: 6956: 6949: 6947: 6945: 6943: 6941: 6939: 6937: 6935: 6931: 6926: 6922: 6918: 6914: 6910: 6906: 6899: 6896: 6891: 6887: 6882: 6877: 6873: 6869: 6865: 6861: 6857: 6846: 6844: 6842: 6838: 6833: 6829: 6824: 6819: 6814: 6809: 6805: 6801: 6797: 6790: 6788: 6786: 6784: 6780: 6776: 6766: 6762: 6757: 6752: 6748: 6744: 6740: 6736: 6732: 6721: 6719: 6717: 6715: 6713: 6711: 6707: 6702: 6698: 6694: 6690: 6686: 6682: 6675: 6673: 6671: 6669: 6667: 6665: 6663: 6661: 6659: 6657: 6655: 6653: 6649: 6644: 6640: 6635: 6630: 6626: 6622: 6619:(9): 1071–5. 6618: 6614: 6610: 6603: 6601: 6599: 6597: 6595: 6591: 6586: 6582: 6577: 6572: 6567: 6562: 6558: 6554: 6553:FASEB Journal 6550: 6543: 6541: 6537: 6532: 6528: 6523: 6518: 6515:(6): 315–21. 6514: 6510: 6506: 6499: 6496: 6491: 6487: 6482: 6477: 6473: 6469: 6465: 6461: 6457: 6450: 6447: 6442: 6438: 6433: 6428: 6424: 6420: 6416: 6412: 6408: 6401: 6398: 6393: 6389: 6384: 6379: 6375: 6371: 6367: 6363: 6359: 6352: 6349: 6344: 6340: 6336: 6332: 6328: 6324: 6320: 6316: 6309: 6306: 6301: 6297: 6293: 6289: 6286:(4): 532–43. 6285: 6281: 6274: 6272: 6268: 6263: 6259: 6254: 6249: 6245: 6241: 6237: 6233: 6229: 6225: 6221: 6214: 6211: 6206: 6202: 6197: 6192: 6188: 6184: 6181:(4): 632–40. 6180: 6176: 6172: 6165: 6162: 6157: 6153: 6149: 6145: 6141: 6137: 6130: 6127: 6122: 6118: 6113: 6108: 6104: 6100: 6096: 6092: 6088: 6081: 6079: 6075: 6070: 6066: 6061: 6056: 6052: 6048: 6045:(2): 569–81. 6044: 6040: 6036: 6029: 6027: 6023: 6018: 6014: 6010: 6006: 6002: 5998: 5994: 5990: 5986: 5979: 5977: 5975: 5973: 5971: 5969: 5967: 5965: 5963: 5961: 5959: 5955: 5950: 5946: 5941: 5936: 5932: 5928: 5924: 5920: 5916: 5909: 5907: 5905: 5903: 5901: 5899: 5897: 5895: 5893: 5891: 5889: 5887: 5885: 5883: 5879: 5874: 5870: 5865: 5860: 5856: 5852: 5848: 5844: 5840: 5833: 5831: 5829: 5825: 5820: 5816: 5812: 5808: 5804: 5800: 5797:(3): 463–87. 5796: 5792: 5785: 5782: 5777: 5773: 5768: 5763: 5758: 5753: 5749: 5745: 5741: 5734: 5731: 5726: 5722: 5718: 5714: 5710: 5706: 5699: 5697: 5695: 5693: 5691: 5689: 5687: 5685: 5681: 5676: 5672: 5668: 5664: 5661:(4): 469–84. 5660: 5656: 5649: 5647: 5643: 5638: 5634: 5629: 5624: 5619: 5614: 5611:(6): 655–64. 5610: 5606: 5602: 5595: 5593: 5589: 5584: 5580: 5575: 5570: 5565: 5560: 5556: 5552: 5548: 5541: 5539: 5537: 5535: 5533: 5531: 5527: 5522: 5518: 5513: 5508: 5504: 5500: 5496: 5492: 5488: 5481: 5479: 5477: 5473: 5468: 5464: 5459: 5454: 5450: 5446: 5442: 5438: 5434: 5427: 5424: 5419: 5415: 5410: 5405: 5401: 5397: 5393: 5389: 5385: 5378: 5376: 5374: 5372: 5370: 5368: 5364: 5359: 5355: 5351: 5347: 5344:(3): 149–60. 5343: 5339: 5332: 5330: 5326: 5321: 5317: 5312: 5307: 5302: 5297: 5293: 5289: 5288: 5283: 5276: 5273: 5268: 5264: 5260: 5256: 5251: 5246: 5242: 5238: 5234: 5227: 5224: 5219: 5215: 5211: 5207: 5200: 5197: 5192: 5188: 5183: 5178: 5173: 5168: 5164: 5160: 5156: 5152: 5148: 5141: 5138: 5133: 5129: 5125: 5121: 5117: 5113: 5106: 5103: 5098: 5094: 5089: 5084: 5079: 5074: 5071:(5): 1441–8. 5070: 5066: 5065:FASEB Journal 5062: 5055: 5052: 5047: 5043: 5038: 5033: 5029: 5025: 5021: 5017: 5013: 5009: 5005: 4998: 4995: 4990: 4986: 4982: 4978: 4975:(3): 227–33. 4974: 4970: 4963: 4960: 4955: 4951: 4947: 4943: 4939: 4935: 4928: 4925: 4920: 4916: 4911: 4906: 4901: 4896: 4892: 4888: 4884: 4877: 4875: 4871: 4866: 4862: 4857: 4852: 4848: 4844: 4841:(3): 200–15. 4840: 4836: 4832: 4825: 4823: 4821: 4819: 4817: 4815: 4813: 4811: 4809: 4807: 4805: 4801: 4796: 4792: 4788: 4784: 4780: 4776: 4772: 4768: 4761: 4759: 4757: 4755: 4753: 4751: 4749: 4747: 4745: 4743: 4741: 4739: 4737: 4735: 4733: 4731: 4729: 4725: 4718: 4714: 4711: 4710: 4706: 4704: 4702: 4697: 4693: 4689: 4685: 4681: 4673: 4671: 4669: 4665: 4661: 4657: 4654: 4649: 4644: 4641: 4638:disease, and 4637: 4636: 4631: 4627: 4623: 4622:periodontitis 4619: 4615: 4606: 4604: 4602: 4598: 4597:phospholipids 4594: 4590: 4586: 4582: 4577: 4573: 4569: 4565: 4561: 4556: 4552: 4548: 4540: 4538: 4536: 4532: 4528: 4524: 4516: 4514: 4512: 4504: 4496: 4492: 4488: 4485:lectrophilic 4484: 4480: 4472: 4464: 4460: 4452: 4450: 4436: 4432: 4428: 4424: 4420: 4416: 4412: 4408: 4404: 4400: 4393: 4390: 4388: 4386: 4378: 4374: 4370: 4366: 4362: 4358: 4354: 4350: 4346: 4338: 4335: 4333: 4327: 4320: 4317: 4314: 4310: 4306: 4302: 4298: 4294: 4288: 4287: 4283: 4280: 4277: 4273: 4269: 4265: 4261: 4257: 4251: 4250: 4246: 4243: 4240: 4236: 4232: 4228: 4224: 4220: 4216: 4212: 4206: 4205: 4201: 4198: 4195: 4192: 4191: 4188: 4165: 4161: 4154: 4151: 4146: 4143: 4139: 4135: 4131: 4127: 4123: 4119: 4115: 4111: 4107: 4103: 4100: 4096: 4092: 4088: 4084: 4080: 4076: 4072: 4068: 4064: 4060: 4056: 4052: 4048: 4044: 4040: 4036: 4032: 4031: 4025: 4022: 4019: 4015: 4011: 4007: 4003: 3999: 3995: 3991: 3988: 3987: 3983: 3980: 3977: 3973: 3969: 3965: 3961: 3957: 3953: 3949: 3946: 3945: 3941: 3938: 3935: 3931: 3927: 3923: 3919: 3915: 3911: 3907: 3903: 3900: 3899: 3895: 3892: 3889: 3885: 3881: 3877: 3873: 3869: 3865: 3861: 3857: 3854: 3853: 3850: 3846: 3842: 3839: 3836: 3832: 3828: 3824: 3820: 3816: 3812: 3808: 3804: 3801: 3800: 3796: 3793: 3790: 3787: 3786: 3783: 3780: 3776: 3772: 3768: 3764: 3760: 3756: 3752: 3748: 3744: 3740: 3736: 3732: 3728: 3724: 3720: 3716: 3712: 3708: 3704: 3700: 3696: 3692: 3688: 3684: 3680: 3672: 3669: 3661: 3654: 3651: 3648: 3642: 3641: 3637: 3634: 3631: 3625: 3624: 3620: 3617: 3614: 3611: 3610: 3607: 3600: 3576: 3569: 3566: 3561: 3557: 3553: 3549: 3545: 3541: 3537: 3533: 3529: 3525: 3521: 3517: 3513: 3509: 3505: 3501: 3497: 3493: 3489: 3485: 3481: 3477: 3473: 3469: 3465: 3461: 3458: 3454: 3451: 3450: 3445: 3442: 3439: 3436: 3433: 3429: 3425: 3421: 3417: 3413: 3409: 3405: 3401: 3398: 3397: 3394: 3391: 3388: 3385: 3382: 3378: 3374: 3370: 3366: 3362: 3358: 3354: 3350: 3347: 3346: 3343: 3339: 3336: 3333: 3330: 3327: 3323: 3319: 3315: 3311: 3307: 3303: 3299: 3295: 3292: 3291: 3288: 3284: 3281: 3278: 3275: 3271: 3268: 3264: 3260: 3256: 3252: 3248: 3244: 3240: 3236: 3233: 3232: 3229: 3226: 3224: 3220: 3217: 3214: 3210: 3206: 3202: 3198: 3194: 3190: 3186: 3182: 3179: 3178: 3174: 3171: 3168: 3165: 3162: 3161: 3158: 3156: 3152: 3148: 3144: 3140: 3135: 3131: 3127: 3123: 3119: 3115: 3111: 3107: 3103: 3099: 3095: 3091: 3090:monooxygenase 3088: 3080: 3077: 3069: 3062: 3059: 3056: 3052: 3048: 3044: 3040: 3036: 3032: 3028: 3022: 3021: 3017: 3014: 3011: 3007: 3003: 2999: 2995: 2992:-trihydroxy-8 2991: 2987: 2983: 2979: 2973: 2972: 2968: 2965: 2962: 2958: 2954: 2950: 2946: 2943:-trihydroxy-9 2942: 2938: 2934: 2930: 2924: 2923: 2919: 2916: 2913: 2909: 2905: 2901: 2897: 2893: 2889: 2885: 2882: 2881: 2877: 2874: 2871: 2867: 2863: 2859: 2855: 2852:-trihydroxy-9 2851: 2847: 2843: 2839: 2836: 2835: 2831: 2828: 2825: 2821: 2817: 2813: 2809: 2806:-trihydroxy-8 2805: 2801: 2797: 2793: 2790: 2789: 2785: 2782: 2779: 2775: 2771: 2767: 2763: 2760:-trihydroxy-8 2759: 2755: 2751: 2747: 2744: 2743: 2739: 2736: 2733: 2730: 2729: 2725: 2720: 2718: 2715: 2711: 2707: 2691: 2690: 2684: 2680: 2676: 2672: 2668: 2667:-nitrosylated 2666: 2661: 2657: 2653: 2649: 2645: 2641: 2637: 2633: 2629: 2625: 2621: 2614: 2611: 2606: 2602: 2598: 2594: 2590: 2586: 2582: 2578: 2574: 2570: 2566: 2562: 2558: 2554: 2550: 2546: 2542: 2538: 2534: 2530: 2526: 2522: 2518: 2514: 2510: 2506: 2502: 2498: 2494: 2493: 2487: 2484: 2481: 2477: 2473: 2469: 2465: 2461: 2457: 2453: 2449: 2446: 2442: 2441: 2437: 2434: 2431: 2427: 2423: 2419: 2415: 2411: 2407: 2403: 2399: 2396: 2392: 2391: 2387: 2384: 2381: 2377: 2373: 2369: 2365: 2361: 2358:-trihydroxy-6 2357: 2353: 2349: 2345: 2342: 2338: 2337: 2334: 2330: 2327: 2324: 2320: 2316: 2312: 2308: 2304: 2301:-trihydroxy-5 2300: 2296: 2292: 2288: 2285: 2281: 2280: 2276: 2273: 2270: 2266: 2262: 2258: 2254: 2250: 2247:-trihydroxy-4 2246: 2242: 2238: 2234: 2231: 2227: 2226: 2223: 2219: 2215: 2211: 2207: 2203: 2200: 2197: 2193: 2189: 2185: 2181: 2177: 2174:-trihydroxy-4 2173: 2169: 2165: 2161: 2154: 2150: 2149: 2145: 2142: 2139: 2135: 2131: 2127: 2123: 2119: 2115: 2111: 2107: 2104: 2103: 2100: 2096: 2093: 2090: 2086: 2082: 2078: 2074: 2070: 2066: 2062: 2058: 2055: 2054: 2050: 2047: 2044: 2040: 2036: 2032: 2028: 2024: 2020: 2016: 2012: 2009: 2008: 2005: 2001: 1998: 1995: 1991: 1987: 1983: 1979: 1975: 1972:-trihydroxy-5 1971: 1967: 1963: 1959: 1956: 1955: 1952: 1948: 1944: 1940: 1936: 1932: 1929: 1926: 1922: 1918: 1914: 1910: 1906: 1903:-trihydroxy-4 1902: 1898: 1894: 1890: 1887: 1886: 1883: 1879: 1875: 1871: 1867: 1863: 1860: 1857: 1853: 1849: 1845: 1841: 1837: 1834:-trihydroxy-4 1833: 1829: 1825: 1821: 1818: 1817: 1813: 1810: 1807: 1804: 1803: 1799: 1794: 1792: 1788: 1784: 1780: 1776: 1772: 1768: 1764: 1760: 1756: 1752: 1748: 1744: 1740: 1736: 1732: 1728: 1724: 1720: 1716: 1712: 1708: 1704: 1700: 1696: 1692: 1688: 1684: 1680: 1676: 1668: 1663: 1659: 1655: 1651: 1647: 1643: 1639: 1635: 1631: 1627: 1623: 1619: 1615: 1614: 1608: 1605: 1602: 1598: 1594: 1590: 1586: 1582: 1578: 1574: 1571: 1570: 1567: 1563: 1559: 1555: 1551: 1548: 1545: 1541: 1537: 1533: 1529: 1525: 1521: 1517: 1514: 1513: 1510: 1506: 1502: 1498: 1495: 1492: 1488: 1484: 1480: 1476: 1473:-trihydroxy-6 1472: 1468: 1464: 1460: 1457: 1453: 1452: 1448: 1444: 1440: 1436: 1432: 1428: 1424: 1420: 1417: 1414: 1410: 1406: 1402: 1398: 1395:-trihydroxy-6 1394: 1390: 1386: 1382: 1379: 1378: 1374: 1371: 1368: 1365: 1364: 1360: 1355: 1353: 1349: 1345: 1341: 1337: 1333: 1330:-RvE3) and 18 1329: 1325: 1321: 1317: 1313: 1309: 1305: 1301: 1297: 1293: 1289: 1285: 1281: 1277: 1273: 1269: 1265: 1261: 1257: 1253: 1249: 1241: 1239: 1237: 1233: 1229: 1225: 1221: 1217: 1213: 1209: 1205: 1201: 1197: 1193: 1189: 1185: 1181: 1175: 1167: 1162: 1158: 1154: 1150: 1146: 1142: 1138: 1135: 1131: 1127: 1123: 1119: 1115: 1111: 1110: 1104: 1101: 1098: 1094: 1090: 1086: 1083:-trihydroxy-6 1082: 1078: 1074: 1070: 1067: 1066: 1063: 1059: 1056: 1053: 1049: 1045: 1041: 1038:-trihydroxy-7 1037: 1033: 1029: 1025: 1022: 1021: 1017: 1014: 1011: 1007: 1003: 999: 996:-trihydroxy-6 995: 991: 987: 983: 980: 979: 976: 972: 968: 965: 962: 958: 954: 950: 947:-trihydroxy-7 946: 942: 938: 934: 931: 930: 926: 923: 920: 917: 916: 912: 907: 905: 900: 897: 893: 889: 885: 881: 877: 873: 869: 865: 861: 857: 853: 849: 845: 841: 837: 834:(or possibly 833: 830: 826: 822: 818: 814: 808: 800: 798: 796: 792: 788: 784: 780: 776: 772: 768: 764: 760: 756: 752: 748: 744: 740: 732: 730: 728: 724: 720: 717:, and kidney 716: 712: 708: 704: 703:smooth muscle 700: 696: 692: 684: 680: 676: 672: 668: 664: 660: 656: 652: 648: 644: 641: 638: 634: 631: 628: 624: 621: 618: 615: 612: 608: 604: 600: 596: 593: 590: 586: 583: 580: 576: 572: 568: 565:; stimulates 564: 560: 556: 552: 548: 544: 540: 536: 532: 528: 524: 523:interleukin-4 520: 516: 512: 509: 506: 502: 499: 496: 493: 490: 486: 482: 478: 474: 470: 467: 466: 465: 463: 459: 455: 451: 447: 443: 439: 435: 426: 424: 421: 417: 413: 409: 405: 401: 397: 393: 389: 385: 381: 377: 373: 369: 365: 361: 357: 353: 349: 345: 341: 337: 333: 329: 325: 321: 317: 313: 309: 305: 301: 297: 293: 289: 285: 281: 277: 273: 270: 266: 262: 259: 255: 251: 243: 241: 239: 234: 232: 228: 224: 220: 216: 212: 208: 207:heart attacks 204: 200: 196: 192: 188: 184: 180: 176: 171: 165: 163: 159: 155: 151: 147: 143: 142:interleukin 1 139: 135: 131: 127: 122: 120: 116: 112: 108: 104: 100: 96: 92: 88: 84: 80: 76: 66: 63: 55: 45: 41: 35: 32:This article 30: 21: 20: 7572:Cell biology 7528: 7524: 7477: 7473: 7467: 7437:(1): 172–8. 7434: 7430: 7424: 7389: 7385: 7375: 7348: 7344: 7334: 7297: 7293: 7283: 7246: 7242: 7232: 7195: 7191: 7181: 7146: 7142: 7086: 7082: 7040: 7036: 7026: 6993: 6983: 6958: 6954: 6908: 6904: 6898: 6863: 6859: 6803: 6799: 6738: 6734: 6684: 6680: 6616: 6612: 6556: 6552: 6512: 6508: 6498: 6466:(1): 81–91. 6463: 6459: 6449: 6414: 6410: 6400: 6365: 6361: 6351: 6318: 6314: 6308: 6283: 6279: 6227: 6223: 6213: 6178: 6174: 6164: 6139: 6135: 6129: 6094: 6090: 6042: 6038: 5995:(1): 26–32. 5992: 5988: 5922: 5918: 5846: 5842: 5794: 5790: 5784: 5747: 5743: 5733: 5708: 5704: 5658: 5654: 5608: 5604: 5554: 5550: 5497:(1): 51–67. 5494: 5490: 5440: 5436: 5426: 5391: 5387: 5341: 5337: 5291: 5285: 5275: 5240: 5236: 5226: 5209: 5205: 5199: 5154: 5150: 5140: 5118:(3): 943–9. 5115: 5111: 5105: 5068: 5064: 5054: 5011: 5007: 4997: 4972: 4968: 4962: 4940:(3): 194–9. 4937: 4933: 4927: 4890: 4886: 4838: 4834: 4770: 4766: 4683: 4677: 4645: 4633: 4630:Lyme disease 4610: 4591:, primarily 4585:isoprostanes 4544: 4520: 4502: 4494: 4490: 4486: 4482: 4458: 4456: 4434: 4426: 4418: 4414: 4410: 4406: 4402: 4398: 4397: 4391: 4376: 4372: 4368: 4364: 4360: 4356: 4352: 4351:-dihydroxy-7 4348: 4344: 4342: 4336: 4331: 4312: 4308: 4304: 4300: 4296: 4275: 4271: 4267: 4263: 4259: 4238: 4234: 4230: 4226: 4222: 4221:-dihydroxy-8 4218: 4214: 4202:Receptor(s) 4193:Trivial name 4163: 4159: 4158: 4152: 4141: 4137: 4133: 4129: 4125: 4121: 4117: 4113: 4112:-dihydroxy-4 4109: 4105: 4098: 4094: 4090: 4086: 4082: 4078: 4074: 4070: 4066: 4062: 4058: 4054: 4050: 4046: 4042: 4038: 4034: 4017: 4013: 4009: 4005: 4001: 3997: 3993: 3975: 3971: 3967: 3963: 3959: 3955: 3951: 3933: 3929: 3925: 3921: 3917: 3913: 3912:-dihydroxy-4 3909: 3905: 3887: 3883: 3879: 3875: 3871: 3867: 3866:-dihydroxy-4 3863: 3859: 3834: 3830: 3826: 3822: 3818: 3814: 3813:-dihydroxy-4 3810: 3806: 3797:Receptor(s) 3788:Trivial name 3746: 3742: 3738: 3734: 3726: 3722: 3718: 3714: 3710: 3706: 3702: 3698: 3690: 3686: 3683:lipoxygenase 3676: 3621:Receptor(s) 3612:Trivial name 3574: 3573: 3567: 3555: 3551: 3547: 3543: 3539: 3535: 3534:-dihydroxy-4 3531: 3527: 3523: 3519: 3515: 3511: 3507: 3503: 3502:-dihydroxy-4 3499: 3495: 3491: 3487: 3483: 3479: 3475: 3471: 3470:-dihydroxy-4 3467: 3463: 3456: 3431: 3427: 3423: 3419: 3415: 3411: 3410:-dihydroxy-4 3407: 3403: 3380: 3376: 3372: 3368: 3364: 3360: 3359:-dihydroxy-4 3356: 3352: 3325: 3321: 3317: 3313: 3309: 3305: 3301: 3297: 3266: 3262: 3258: 3254: 3250: 3246: 3245:-dihydroxy-4 3242: 3238: 3212: 3208: 3204: 3200: 3196: 3192: 3191:-dihydroxy-4 3188: 3184: 3163:Trivial name 3150: 3146: 3143:diastereomer 3138: 3113: 3109: 3105: 3101: 3096: and 3084: 3076:Protectin D1 3054: 3050: 3046: 3042: 3038: 3037:-dihydroxy-8 3034: 3030: 3009: 3005: 3001: 2997: 2993: 2989: 2985: 2981: 2960: 2956: 2952: 2948: 2944: 2940: 2936: 2932: 2911: 2907: 2903: 2899: 2895: 2894:-dihydroxy-8 2891: 2887: 2869: 2865: 2861: 2857: 2853: 2849: 2845: 2841: 2823: 2819: 2815: 2811: 2807: 2803: 2799: 2795: 2777: 2773: 2769: 2765: 2761: 2757: 2753: 2749: 2740:Receptor(s) 2731:Trivial name 2713: 2705: 2687: 2674: 2670: 2664: 2660:atorvastatin 2654:or with the 2639: 2635: 2631: 2627: 2623: 2619: 2618: 2612: 2592: 2588: 2584: 2580: 2576: 2572: 2571:-dihyrdoxy-4 2568: 2564: 2560: 2556: 2552: 2548: 2544: 2540: 2536: 2528: 2524: 2520: 2516: 2512: 2508: 2504: 2479: 2475: 2471: 2467: 2463: 2459: 2458:-dihydroxy-5 2455: 2451: 2444: 2429: 2425: 2421: 2417: 2413: 2409: 2408:-dihydroxy-4 2405: 2401: 2394: 2379: 2375: 2371: 2367: 2363: 2359: 2355: 2351: 2347: 2340: 2322: 2318: 2314: 2310: 2306: 2302: 2298: 2294: 2290: 2283: 2268: 2264: 2260: 2256: 2252: 2248: 2244: 2240: 2236: 2229: 2195: 2191: 2187: 2183: 2179: 2175: 2171: 2167: 2163: 2152: 2137: 2133: 2129: 2125: 2121: 2117: 2116:-dihydroxy-5 2113: 2109: 2088: 2084: 2080: 2076: 2072: 2068: 2067:-dihydroxy-4 2064: 2060: 2042: 2038: 2034: 2030: 2026: 2022: 2018: 2014: 1993: 1989: 1985: 1981: 1977: 1973: 1969: 1965: 1961: 1924: 1920: 1916: 1912: 1908: 1904: 1900: 1896: 1892: 1855: 1851: 1847: 1843: 1839: 1835: 1831: 1827: 1823: 1814:Receptor(s) 1805:Trivial name 1790: 1786: 1782: 1778: 1774: 1770: 1766: 1762: 1758: 1754: 1750: 1746: 1742: 1738: 1734: 1730: 1726: 1722: 1718: 1714: 1710: 1706: 1702: 1694: 1690: 1686: 1682: 1678: 1674: 1672: 1600: 1596: 1592: 1588: 1584: 1583:-dihydroxy-5 1580: 1576: 1543: 1539: 1535: 1531: 1527: 1526:-dihydroxy-6 1523: 1519: 1490: 1486: 1482: 1478: 1474: 1470: 1466: 1462: 1455: 1412: 1408: 1404: 1400: 1396: 1392: 1388: 1384: 1375:Receptor(s) 1366:Trivial name 1351: 1347: 1343: 1339: 1335: 1331: 1327: 1323: 1319: 1315: 1311: 1307: 1303: 1299: 1295: 1287: 1283: 1279: 1275: 1263: 1259: 1255: 1251: 1247: 1245: 1235: 1231: 1227: 1223: 1219: 1215: 1211: 1207: 1199: 1195: 1191: 1187: 1183: 1177: 1096: 1092: 1088: 1084: 1080: 1076: 1072: 1051: 1047: 1043: 1039: 1035: 1031: 1027: 1009: 1005: 1001: 997: 993: 989: 985: 960: 956: 952: 948: 944: 940: 936: 927:Receptor(s) 918:Trivial name 895: 891: 887: 883: 879: 867: 859: 847: 843: 828: 824: 820: 816: 812: 810: 786: 782: 778: 766: 762: 758: 754: 750: 746: 736: 733:Biochemistry 715:goblet cells 688: 637:MHC class II 575:cytotoxicity 547:amphiregulin 460:, etc. (see 430: 427:Inflammation 412:double bonds 352:hydroxylated 332:leukotrienes 283: 268: 258:oligopeptide 253: 247: 235: 170:pathological 166: 160: and 158:Biosynthesis 128:) including 123: 111:inflammation 95:lipoxygenase 82: 78: 74: 73: 58: 49: 33: 7582:Fatty acids 6687:: 108–115. 4773:(1): 3–22. 4618:peritonitis 4531:neutrophils 4527:mouse brain 4077:-diHDHA, 14 4069:-diHDHA, 14 3599:peritonitis 3172:Receptor(s) 3155:neutrophils 2679:neutrophils 2601:peritonitis 2597:eosinophils 2497:chemosensor 2331:stimulates 2204:stimulates 2097:stimulates 2002:stimulates 1933:stimulates 1864:stimulates 1650:lymphocytes 1499:stimulates 1421:stimulates 1310:-HETE or 18 1153:lymphocytes 1149:spinal cord 1137:fibroblasts 1126:macrophages 1118:eosinophils 1114:neutrophils 1060:stimulates 969:Stimulates 876:prostanoids 858:form the 15 781:−3 DPA are 711:osteoblasts 707:osteoclasts 699:fibroblasts 695:endothelium 595:Macrophages 579:eosinophils 511:Lymphocytes 495:Eosinophils 469:Neutrophils 388:eosinophils 380:neutrophils 376:macrophages 7577:Immunology 7566:Categories 5849:: 144–55. 5750:: 181–92. 5557:: 830930. 4719:References 4523:anandamide 4489:atty acid 4461:−3 DPA by 4199:Activities 4174:, and MaR3 3901:7-epi-MaR1 3794:Activities 3618:Activities 3276:activation 3180:PD1 (NPD1) 3169:Activities 3141:-hydroxyl 2737:Activities 2722:See also: 2700:, and RvD5 2662:, to form 2539:-hydroxy-4 1811:Activities 1796:See also: 1646:mast cells 1449:receptors 1372:Activities 1357:See also: 1145:astrocytes 1141:epithelium 924:Activities 909:See also: 745:(DHA), or 691:epithelium 623:Mast cells 479:receptor, 372:mast cells 296:chemokines 146:annexin A1 119:protectins 52:March 2022 6994:Biochimie 6905:Biochimie 6775:CIP rules 6321:: 57–66. 6230:: 18972. 5711:: 49–63. 4893:(1): 61. 4628:disease, 2644:platelets 1777:-epoxy-17 1761:-epoxy-17 1662:glutamate 1618:chemokine 1350:-RvE2. 18 1306:-RvE1. 18 1272:bacterial 1168:Resolvins 1122:monocytes 904:receptors 899:chirality 862:-hydroxy 719:podocytes 673:, and/or 639:proteins. 627:histamine 617:Microglia 599:phenotype 585:Platelets 571:apoptosis 501:Monocytes 489:apoptosis 485:phagocyte 477:chemokine 384:monocytes 364:5-oxo-ETE 288:cytokines 199:psoriasis 175:pathogens 115:resolvins 7555:24656045 7525:Immunity 7502:20136504 7494:25061854 7459:31721094 7451:22834636 7416:23956430 7367:27422370 7326:21757729 7275:22566962 7224:19965612 7173:25200603 7121:23736886 7089:: 1940. 7059:16424216 7018:31338779 7010:25223888 6975:26545300 6961:: 1–18. 6925:24262603 6890:31793912 6832:36499209 6765:34890076 6701:26546723 6643:26236990 6585:25713027 6531:25012818 6490:26474728 6441:25392529 6392:27994074 6343:34108750 6335:24929111 6300:22204329 6262:26743932 6205:23747022 6156:22326554 6121:21963090 6069:21206090 6017:45820130 6009:26655290 5949:25359497 5873:26546247 5811:16968948 5776:26457057 5725:25895638 5675:25149823 5637:27052783 5583:26339646 5521:26688348 5467:25726564 5418:25139562 5358:25911383 5320:30705632 5294:: 1582. 5259:19630766 5097:21532053 5046:24899309 4989:26095908 4954:25944272 4919:26965310 4865:25857211 4795:10160642 4787:25052386 4707:See also 4429:−3 DPA ( 4385:exudates 4182:and MaR2 3681:, other 3662:Maresins 3560:planaria 3274:platelet 2683:hydroxyl 2605:planaria 1622:NK cells 1616:CMKLR1 ( 1552:partial 1174:Resolvin 1163:enzymes. 1134:synovial 801:Lipoxins 775:lipoxins 607:cytokine 589:clotting 450:diabetes 420:in vitro 408:hydroxyl 223:dementia 215:diabetes 183:rhinitis 7546:4004957 7407:3810452 7317:3173121 7266:3342038 7215:2853460 7164:4224612 7112:3672887 7091:Bibcode 6911:: 1–7. 6881:6934227 6854:n-3 DPA 6823:9738788 6756:9305452 6729:n-3 DPA 6634:4560998 6576:4415017 6481:4710564 6432:4258475 6383:5225078 6253:4705531 6232:Bibcode 6196:3732499 6112:3200462 6060:3026718 5940:4315926 5864:4854800 5819:6496181 5767:4598198 5628:7399282 5574:4538417 5512:5242505 5458:4490858 5409:4324013 5311:6344435 5267:3394218 5218:2585721 5191:6089195 5159:Bibcode 5132:6422933 5088:3228345 5037:4263681 5016:Bibcode 4910:4787218 4856:4515371 4696:dry eye 4640:corneal 4379:-diHDPA 4196:Formula 3791:Formula 3695:epoxide 3668:Maresin 3615:Formula 3589:and PD2 3581:and PD2 3166:Formula 3118:epoxide 3063:GPR101 2734:Formula 2714:E. coli 2689:E. coli 2648:aspirin 2155:-RvD1 ( 1808:Formula 1654:neurons 1638:myeloid 1369:Formula 1147:in the 1130:T cells 921:Formula 894:versus 856:aspirin 836:ALOX15B 807:Lipoxin 741:(EPA), 705:cells, 697:cells, 693:cells, 643:Neurons 446:obesity 416:lipoxin 368:signals 362:(e.g. 350:), the 348:12-HETE 342:(e.g., 298:(e.g. 244:History 211:strokes 38:Please 7553: 7543: 7500: 7492: 7457: 7449: 7414: 7404: 7365: 7324: 7314: 7273: 7263: 7249:: 81. 7222: 7212: 7171: 7161: 7119: 7109: 7057: 7016: 7008: 6973: 6923: 6888: 6878: 6830: 6820: 6763: 6753: 6699: 6641: 6631: 6583: 6573: 6529: 6488: 6478: 6439: 6429: 6390: 6380: 6341: 6333: 6298: 6260: 6250: 6203: 6193: 6154: 6119: 6109: 6067: 6057: 6015: 6007: 5947: 5937: 5871: 5861: 5817: 5809: 5774: 5764: 5723: 5673: 5635: 5625: 5581: 5571: 5519: 5509: 5465: 5455: 5416: 5406: 5356: 5318: 5308: 5265: 5257: 5216: 5189: 5182:391698 5179: 5130: 5095: 5085: 5044: 5034: 5008:Nature 4987: 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