Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals.
Charles N. Serhan,Song Hong,Karsten Gronert,Sean P. Colgan,Pallavi R. Devchand,Gudrun E. Mirick,Rose-Laure Moussignac +6 more
TLDR
It is reported that lipidomic analysis of exudates obtained in the resolution phase from mice treated with ASA and docosahexaenoic acid produce a novel family of bioactive 17R-hydroxy-containing di- and tri-Hydroxy-docosanoids termed resolvins.Abstract:
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 17 R -hydroxy-containing di- and tri-hydroxy-docosanoids termed resolvins. Murine brain treated with aspirin produced endogenous 17 R -hydroxydocosahexaenoic acid as did human microglial cells. Human COX-2 converted DHA to 13-hydroxy-DHA that switched with ASA to 17 R -HDHA that also proved a major route in hypoxic endothelial cells. Human neutrophils transformed COX-2-ASA‐derived 17 R -hydroxy-DHA into two sets of novel diand trihydroxy products; one initiated via oxygenation at carbon 7 and the other at carbon 4. These compounds inhibited (IC 50 � 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 17 R -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.read more
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Resolving inflammation : dual anti-inflammatory and pro-resolution lipid mediators
TL;DR: New cellular and molecular mechanisms for the resolution of inflammation are presented, revealing key roles for eicosanoids, such as lipoxins, and recently discovered families of endogenous chemical mediators, termed resolvins and protectins, which have anti-inflammatory and pro-resolution properties.
Journal ArticleDOI
n−3 Polyunsaturated fatty acids, inflammation, and inflammatory diseases
TL;DR: At sufficiently high intakes, long-chain n-3 polyunsaturated fatty acids (PUFAs), as found in oily fish and fish oils, decrease the production of inflammatory eicosanoids, cytokines, and reactive oxygen species and the expression of adhesion molecules, and are potentially potent antiinflammatory agents.
Journal ArticleDOI
Resolution of inflammation: the beginning programs the end.
Charles N. Serhan,John Savill +1 more
TL;DR: Emerging evidence now suggests that an active, coordinated program of resolution initiates in the first few hours after an inflammatory response begins, and the mechanism required for inflammation resolution may underpin the development of drugs that can resolve inflammatory processes in directed and controlled ways.
Journal ArticleDOI
Pro-resolving lipid mediators are leads for resolution physiology
TL;DR: The mechanisms of specialized pro-resolving mediators and omega-3 essential fatty acid pathways that could help us to understand their physiological functions are covered.
Journal ArticleDOI
The opposing effects of n-3 and n-6 fatty acids
Gerd Schmitz,Josef Ecker +1 more
TL;DR: In this article, the authors classified polyunsaturated fatty acids (PUFAs) in n-3 fatty acids and n-6 fatty acids, and in westernized diet the predominant dietary PUFAs are n- 6 fatty acids.
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