Resolvins

By C. Serhan, Song Hong, K. Gronert, S. Colgan, P. Devchand, Gudrun E Mirick, Rose-Laure Moussignac. Journal of Experimental Medicine, 2002

1,680 citations recorded by the source corpus.

Aspirin (ASA) is unique among current therapies because it acetylates cyclooxygenase (COX)-2 enabling the biosynthesis of R-containing precursors of endogenous antiinflammatory mediators. Here, we report that lipidomic analysis of exudates obtained in the resolution phase from mice treated with ASA and docosahexaenoic acid (DHA) (C22:6) produce a novel family of bioactive 17R-hydroxy-containing di- and tri-hydroxy-docosanoids termed resolvins. Murine brain treated with aspirin produced endogenous 17R-hydroxydocosahexaenoic acid as did human microglial cells. Human COX-2 converted DHA to 13-hydroxy-DHA that switched with ASA to 17R-HDHA that also proved a major route in hypoxic endothelial cells. Human neutrophils transformed COX-2-ASA–derived 17R-hydroxy-DHA into two sets of novel di- and trihydroxy products; one initiated via oxygenation at carbon 7 and the other at carbon 4. These compounds inhibited (IC50 ∼50 pM) microglial cell cytokine expression and in vivo dermal inflammation and peritonitis at ng doses, reducing 40–80% leukocytic exudates. These results indicate that exudates, vascular, leukocytes and neural cells treated with aspirin convert DHA to novel 17R-hydroxy series of docosanoids that are potent regulators. These biosynthetic pathways utilize omega-3 DHA and EPA during multicellular events in resolution to produce a family of protective compounds, i.e., resolvins, that enhance proresolution status.

Subfields: Biochemistry, Nutrition and Dietetics, Pharmacology

View Paper: https://www.semanticscholar.org/paper/1cdc97b0e8210244fce6f50a8f9e51c1011704fd

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Biochemistry

1. C. Serhan
2. P. Calder
3. Undurti N. Das
4. D. Gilroy
5. N. Petasis
6. Chia Nan
7. M. Perretti
8. C. Buckley

In Nutrition and Dietetics

1. C. Serhan
2. P. Calder
3. D. Gilroy
4. Undurti N. Das
5. N. Petasis
6. Chia Nan
7. M. Perretti
8. C. Buckley

In Pharmacology

1. C. Serhan
2. P. Calder
3. Undurti N. Das
4. Chia Nan
5. N. Petasis
6. J. Tschopp
7. Simon C. Dyall

Citations in the corpus

• The mouse retina as an angiogenesis model. (2010, background): “Cyclooxygenase (Cox)-2, one of the key metabolizing enzymes for -3 and -6 PUFAs, has been independently identified as a strong modulator of proliferative retinopathy in the OIR retina(128); Serhan et al.(129) showed that Cox-2 modulation via aspirin can generate anti-inflammatory lipid mediators of ”
• Resolution of inflammation: state of the art, definitions and terms (2006, background): “Additionally, the widely used aspirin jump-starts resolution by making up for its loss in prostaglandin production, which plays key roles in resolution, by instead generating the epimeric version of lipid mediators (25), such as the aspirin-triggered lipoxins (recently reviewed in ref.”
• Advances in Our Understanding of Oxylipins Derived from Dietary PUFAs. (2015, background): “DHA also has been shown to yield hydroxy Oxylipins 517 FAs nonenzymatically (e.g., 8-HDoHE) (99, 100), and 13- HDoHE can be formed via COX2 (26).”
• Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1 (2005, background): “Recently, we uncovered a novel family of aspirin-triggered bioactive lipids biosynthesized during the spontaneous resolution phase of acute inflammation in vivo, coined the resolvins (resolution-phase interaction products), which are potent autacoids that now may provide molecular means that underli”
• Resolvin D1 binds human phagocytes with evidence for proresolving receptors (2010, methodology): “RvD1 limits PMN infiltration at nanogram levels in murine peritonitis and blocks transendothelial migration of human PMNs (8, 12) as well as enhances phagocytosis by human macrophages (MΦ) (13).”
• Essential fatty acids: biochemistry, physiology and pathology (2006, background): “Murine brain cells expressing COX-2, when treated with aspirin, enzymatically transformed DHA to a 17R series of hydroxy DHAs (HDHAs) that, in turn, is enzymatically converted by PMNs to di- and tri-hydroxy containing docosanoids [91].”
• Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA (2015, background): “, 2014), and consitent with the formation of resolvins from DHA (Serhan et al., 2002), aspirin acetylation of COX-2 also significantly increases production of EFOXs.”
• Inflammatory Resolution: new opportunities for drug discovery (2004, background): “DHA and EPA — omega-3 fatty-acid constituents of fish oils — were shown recently to be metabolized during the resolving phase of an aspirin-treated TNF-α-induced inflammation to potent anti-inflammatory products, aptly named resolvin”
• Polyunsaturated fatty acids and inflammatory processes: New twists in an old tale. (2009, background): “The identification of these novel EPA- and DHAderived mediators is an exciting new area of n-3 fatty acids and inflammation and the implications to a variety of conditionsmay be of great importance [25,29,30].”