Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators, and their endogenous aspirin-triggered epimers.
The molecular basis for the beneficial impact of essential omega-3 (n-3) FA remains of interest. Recently, we identified novel mediators generated from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that displayed potent bioactions identified first in resolving inflammatory exudates and in tissues enriched with DHA. The trivial names resolvin (resolution phase interaction products) and docosatrienes were introduced for the bioactive compounds from these novel series since they possess potent anti-inflammatory and immunoregulatory actions. Compounds derived from EPA carrying potent biological actions (i.e., 1-10 nM range) are designated E series and denoted resolvins of the E series (resolvin E1 or RvE1), and those biosynthesized from the precursor DHA are denoted resolvins of the D series (resolvin D1 or RvD1). The number 1 designates the bioactive compounds in this family (#1-4). Bioactive members from DHA-containing conjugated triene structures or docosatrienes (DT) that possess immunoregulatory and neuroprotective actions were termed neuroprotectins. Aspirin treatment initiates a related epimeric series by triggering endogenous formation of the 17R-D series resolvins and docosatrienes. These epimers are denoted as aspirin-triggered (AT)-RvD and DT, and possess potent anti-inflammatory actions in vivo essentially equivalent to their 17S series pathway products. These include five distinct series: (i) 18R resolvins from EPA (i.e., RvE1); (ii) 17R series (AT) resolvins from DHA (RvD1 through RvD4); (iii) 17S series resolvins from DHA (RvD1 through RvD4), (iv) DT from DHA; and (v) their AT form 17R series DT. In this article, we provide an overview of the formation and actions of these newly uncovered pathways and products.
Serhan
Charles N
CN
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. cnserhan@zeus.bwh.harvard.edu
Arita
Makoto
M
Hong
Song
S
Gotlinger
Katherine
K
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000737:chemistry / Q000378:metabolism*; D015118:Eicosapentaenoic Acid / Q000737:chemistry / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D018696:Neuroprotective Agents / Q000737:chemistry* / Q000378:metabolism
D015525:Fatty Acids, Omega-3; D018696:Neuroprotective Agents; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D001241:Aspirin
Nutr Rev. 1973 Aug;31(8):248-9
4586201
Lipids. 2001 Sep;36(9):945-59
11724467
Biochemistry. 2000 Mar 7;39(9):2376-83
10694406
FASEB J. 2003 Apr;17(6):652-9
12665478
J Biol Chem. 2003 Oct 31;278(44):43807-17
12923200
Science. 2002 Apr 19;296(5567):474-5
11964462
J Clin Invest. 1984 Dec;74(6):1922-33
6096400
Nature. 2003 Jul 3;424(6944):88-93
12840763
Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15579-84
15496467
Lab Invest. 1994 Sep;71(3):380-6
7523762
Circulation. 2002 Apr 23;105(16):1897-903
11997274
Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8491-6
15152078
J Clin Invest. 1990 Mar;85(3):772-80
2155925
Prostaglandins Other Lipid Mediat. 2002 Aug;68-69:211-34
12432920
N Engl J Med. 1980 Jul 3;303(1):27-34
6246431
Prostaglandins Leukot Essent Fatty Acids. 2003 Mar;68(3):213-8
12591005
JAMA. 2004 Feb 4;291(5):585-90
14762037
Nat Med. 2002 Nov;8(11):1296-302
12368905
Mol Pharmacol. 2003 Sep;64(3):721-30
12920210
J Pharmacol Exp Ther. 2002 Feb;300(2):385-92
11805195
JAMA. 2004 Feb 4;291(5):623-4
14762043
Proc Natl Acad Sci U S A. 1984 Sep;81(17):5335-9
6089195
Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):2135-9
14766977
J Dent Res. 2003 Feb;82(2):82-90
12562878
J Clin Invest. 2001 Jun;107(12):1481-9
11413151
J Exp Med. 2005 Mar 7;201(5):713-22
15753205
Biochemistry. 1994 Feb 1;33(4):856-63
8305432
Proc Natl Acad Sci U S A. 1983 Jun;80(12):3581-4
6304720
J Immunol. 2003 Dec 15;171(12):6856-65
14662892
J Neurochem. 1994 Jun;62(6):2437-47
8189247
Lancet. 1999 Aug 7;354(9177):447-55
10465168
Nat Genet. 2004 Mar;36(3):233-9
14770184
J Biol Chem. 2003 Apr 25;278(17):14677-87
12590139
J Immunol. 2000 Feb 15;164(4):1663-7
10657608
J Immunol. 2003 Mar 1;170(5):2688-94
12594298
Lipids. 2003 Apr;38(4):317-21
12848276
Kidney Int. 2003 Aug;64(2):480-92
12846743
J Biol Chem. 1992 Aug 15;267(23):16168-76
1322894
Science. 2002 Apr 19;296(5567):539-41
11964481
J Exp Med. 1996 Jan 1;183(1):137-46
8551217
J Am Coll Nutr. 1999 Oct;18(5):487-9
10511332
J Biol Chem. 1984 May 10;259(9):5776-83
6232277
J Biol Chem. 1996 Sep 13;271(37):22663-71
8798438
J Immunol. 2002 May 15;168(10):5260-7
11994483
J Exp Med. 2002 Oct 21;196(8):1025-37
12391014
FEBS Lett. 1999 Apr 16;449(1):7-11
10225417
Prostaglandins Other Lipid Mediat. 2002 Aug;68-69:303-12
12432925
J Exp Med. 2000 Oct 16;192(8):1197-204
11034610
Prostaglandins Other Lipid Mediat. 2002 Aug;68-69:235-43
12432921
J Exp Med. 1994 Jul 1;180(1):253-60
8006586
Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9475-9
7568157