BioAcyl Corp
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Serhan, C. N., Hong, S., & Gronert, K. (2002). Resolvins: A Family of Bioactive Products of Omega-3 Fatty Acid Transformation Circuits Initiated by Aspirin Treatment that Counter Proinflammation Signals. Journal of Experimental Medicine, 196(8), 1025–1037. Added by: Dr. Enrique Feoli (12/10/2023, 19:14) Last edited by: Dr. Enrique Feoli (12/10/2023, 19:16) |
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| Resource type: Journal Article DOI: 10.1084/jem.20020760 ID no. (ISBN etc.): 0022-1007 BibTeX citation key: Serhan2002 View all bibliographic details  |
Categories: BioAcyl Corp Subcategories: Constitutive innate immunity Creators: Gronert, Hong, Serhan Collection: Journal of Experimental Medicine |
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| Abstract |
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{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. }
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