Pro-resolving actions and stereoselective biosynthesis of 18S E-series resolvins in human leukocytes and murine inflammation

Oh, Sungwhan F.; Pillai, Padmini S.; Recchiuti, Antonio; Rong, Yang; Serhan, Charles N.

doi:10.1172/jci42545

Cited by 258 publications

(323 citation statements)

References 57 publications

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“…These results agree with Oh et al ( 19 ) who showed that total concentration of 18-HEPE was not altered after a single dose of fi sh oil and aspirin.…”

Section: Discussionsupporting

confidence: 93%

Short-term n-3 fatty acid supplementation but not aspirin increases plasma proresolving mediators of inflammation

Barden

Mas

Croft

et al. 2014

Journal of Lipid Research

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the infl ammatory process ( 1, 2 ), acting on a number of G-coupled protein receptors, including the leukotriene B4 (LTB 4 ) receptor to affect resolution of infl ammation.Metabolism of EPA by acetylated cyclooxygenase (COX)-2 or cytochrome P450 monooxygenase results in the formation of 18-hydroxyeicosapentaenoic acid (18-HEPE) that can be converted by 5-lipoxygenase (LOX) to 5-hydroperoxy-18-hydroxyeicosapentaenoic acid (5-Hp-18-HEPE). The latter can undergo epoxidation and enzyme hydrolysis to yield resolvin E1 (RvE1), or reduction to yield resolvin E2 (RvE2). A third E-series resolvin, resolvin E3 (RvE3), is generated from EPA by the 12/15 LOX pathway ( 3 ). Studies using chiral chromatography indicate that acetylation of COX-2 by aspirin generates both 18S-HEPE and 18R-HEPE and their respective downstream E-series resolvins 18S-RvE1 and 18R-RvE1 ( 4 ).Metabolism of DHA by either acetylated COX-2 or 15-LOX gives rise to 17-hydroperoxydocosahexaenoic acid (17-HpDHA) that is converted to 17-hydroxydocosahexaenoic acid (17-HDHA). 15-LOX gives rise to mainly 17S-HpDHA whereas acetylated COX-2 yields 17R-HpDHA ( 5 ). The action of 5-LOX on 17-HDHA generates the Dseries resolvins RvD1-RvD6 ( 1 ). In the absence of 5-LOX, protectin D1 (PD1) is formed from 17-HpDHA. In macrophages, 12/15-LOX can act on DHA to form 14-hydroperoxydocosahexaenoic acid (14-HpDHA) that can be further metabolized to 14-hydroxydocosahexaenoic acid (14-HDHA) and the maresins ( 6 ).Most of the research on the effects of SPMs has been in animal models. The resolvins and protectins have been Abstract Resolution of infl ammation is an active process involving specialized proresolving mediators (SPM) formed from the n-3 fatty acids. This study examined the effect of n-3 fatty acid supplementation and aspirin on plasma SPMs in healthy humans. Healthy volunteers (n = 21) were supplemented with n-3 fatty acids (2.4g/day) for 7 days with random assignment to take aspirin (300 mg/day) or placebo from day 5 to day 7. Blood was collected at baseline (day 0 There is increasing interest in the role of the specialized proresolving mediators (SPMs) that actively stimulate resolution of infl ammation ( 1 ). In particular, recent attention has focused on those SPM derived from the long-chain n-3 fatty acids EPA and DHA. The SPMs formed from EPA are known as E-series resolvins, while those formed from DHA include protectins, D-series resolvins, and maresins ( 1 ). Studies have shown that SPMs increase with time during A.B., T.A.M.,)

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“…These results agree with Oh et al ( 19 ) who showed that total concentration of 18-HEPE was not altered after a single dose of fi sh oil and aspirin.…”

Section: Discussionsupporting

confidence: 93%

Short-term n-3 fatty acid supplementation but not aspirin increases plasma proresolving mediators of inflammation

Barden

Mas

Croft

et al. 2014

Journal of Lipid Research

View full text Add to dashboard Cite

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“…Thus measurement of 18R/S-HEPE may represent total EPA-derived resolvin capacity. The enantionmers 18S-HEPE and 18R-HEPE can be resolved with baseline resolution by using chiral chromatography (19 ). Our analyses showed that 17S-HDHA and 17R-HDHA eluted as a single peak on LCMSMS and had the same fragmentation pattern (data not shown).…”

Section: Discussionmentioning

confidence: 75%

Resolvins D1, D2, and Other Mediators of Self-Limited Resolution of Inflammation in Human Blood following n-3 Fatty Acid Supplementation

et al. 2012

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BACKGROUND Resolvins and protectins are families of local lipid mediators generated from the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) during self-limited resolution of inflammation. We aimed to develop a liquid chromatography–tandem mass spectrometry (LC-MS/MS) assay to measure these lipid mediators in human blood following n-3 fatty acid supplementation and to determine whether the blood collection method affects their measured concentration. METHODS Blood samples from 20 healthy volunteers enrolled in an n-3 fatty acid supplementation trial were collected in EDTA, heparin, or citrate, or prepared as serum after volunteers had undergone 3 weeks of supplementation. Plasma or serum was purified by solid-phase chromatography and analyzed with LC-MS/MS. RESULTS The assay identified 18R/S-hydroxy-5Z,8Z,11Z,14Z,16E-eicosapentaenoic acid (18R/S-HEPE); 17S-hydroxy-4Z,7Z,10Z,13Z,15E,19Z-docosahexaenoic acid (17R/S-HDHA); 7S,8R,17S-trihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid (RvD1); 7S,8R,17R-trihydroxy-4Z,9E,11E,13Z,15E19Z-docosahexaenoicacid (17R-RvD1); 7S,16R,17S-trihydroxy-4Z,8E,10Z,12E,14E,19Z-docosahexaenoic acid (RvD2); 10S,17S-dihydroxy-4Z,7Z,11E,13Z,15E,19Z-docosahexaenoicacid (10S,17S-DiHDHA); and 10R,17S-dihydroxy-4Z,7Z,11E,13E,15Z,19Z-docosahexaenoic acid (protectin D1, PD1). The limits of detection and quantification were 3 pg and 6 pg on-column, respectively. The pathway precursors 18R/S-HEPE and 17R/S-HDHA, but not the resolvins, were lower in serum compared with plasma. After n-3 fatty acid supplementation, mean (SD) EDTA plasma concentrations were: 18R/S-HEPE 386 (56) pg/mL, 17R/S-HDHA 365 (65) pg/mL, RvD2 26 (4) pg/mL, RvD1 31 (5) pg/mL, and 17R-RvD 161 (7) pg/mL. 10S,17S-DiHDHA and PD1 concentrations were below the limit of quantification. CONCLUSIONS This is the first study reporting 17R/S-HDHA, RvD1, and RvD2 concentrations measured in human blood following oral n-3 fatty acid supplementation. The concentrations of the antiinflammatory lipid mediators RvD1 and RvD2 were within the biological range known to have antiinflammatory and proresolving activities in isolated human leukocytes and in in vivo studies in mice.

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“…17,18 ), and maresins (MaR). These have been termed specialised pro-resolving mediators (SPM) since they are involved in the clearance and regulation of inflammatory substances 19,20 . Numbers in the PG and TX shorthand notation represent the number of double bonds in the molecule; the double bonds can be used for formation of cyclic-or oxy-derivatives.…”

Section: Fatty Acids As Precursors Of Lipid Mediatorsmentioning

confidence: 99%

Fatty Acids as Biocompounds: Their Role in Human Metabolism, Health and Disease - A Review. Part 2: Fatty Acid Physiological Roles and Applications in Human Health and Disease

Kremmyda¹,

Tvrzická²,

Staňková³

et al. 2011

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

154

134

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Background. This is the second of two review parts aiming at describing the major physiological roles of fatty acids, as well as their applications in specific conditions related to human health.Results. The review included the current literature published in Pubmed up to March 2011. In humans, fatty acids are a principle energy substrate and structural components of cell membranes (phospholipids) and second messengers. Fatty acids are also ligands of nuclear receptors affecting gene expression. Longer-chain (LC) polyunsaturated fatty acids (PUFA), including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid are precursors of lipid mediators such as eicosanoids (prostaglandins, leukotrienes, thromboxanes), resolvins and neuroprotectins. Lipid mediators produced by EPA and DHA (LC n-3 PUFA; mainly found in oily fish) are considered as inflammation-resolving, and thus, fish oil has been characterised as antiinflammatory. Recommendations for EPA plus DHA intake from oily fish vary between 250-450 mg/day. Dietary reference values for fat vary between nutrition bodies, but mainly agree on a low total and saturated fat intake. The existing literature supports the protective effects of LC n-3 PUFA (as opposed to n-6 PUFA and saturated fat) in maternal and offspring health, cardiovascular health, insulin sensitivity, the metabolic syndrome, cancer, critically ill patients, and immune system disorders.Conclusion. Fatty acids are involved in multiple pathways and play a major role in health. Further investigation and a nutrigenomics approach to the effects of these biocompounds on health and disease development are imperative and highlight the importance of environmental modifications on disease outcome.humans. Thus, these FA may be characterised as conditionally essential depending on EFA availability. Genetic variation in human desaturase genes affects FA metabolism, plasma lipid profiles, and risk of disease development [5][6][7] . Recommendations for minimum dietary intake of EPA plus DHA vary between 250-450 mg/day 8 , especially for pregnant women and those of reproductive age. Rich sources of LC n-3 PUFA are fish oils and the flesh of oily fish, whereas non-oily (white) fish contain them but in lower amounts.Long-chain PUFA with 18-20 carbon atoms, including EPA and AA, are precursors of eicosanoids (prostaglandins, leucotrienes and thromboxanes), which have a broad scale of regulatory, autocrine and paracrine effects. Long-chain PUFA with 20 and 22 carbon atoms are precursors of autacoids -resolvins (resolution phase interaction products), lipoxins and neuroprotectins 9 . FA are also ligands of nuclear receptors which take part in the subcellular control of metabolic pathways. Covalent modification of proteins by FA acylation enables their incorporation into membranes. Hydroxy FA are activators of some nuclear factors and are responsible for the expression of proinflammatory cytokines (interleukin (IL)-1,

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Pro-resolving actions and stereoselective biosynthesis of 18S E-series resolvins in human leukocytes and murine inflammation

Cited by 258 publications

References 57 publications

Short-term n-3 fatty acid supplementation but not aspirin increases plasma proresolving mediators of inflammation

Short-term n-3 fatty acid supplementation but not aspirin increases plasma proresolving mediators of inflammation

Resolvins D1, D2, and Other Mediators of Self-Limited Resolution of Inflammation in Human Blood following n-3 Fatty Acid Supplementation

Fatty Acids as Biocompounds: Their Role in Human Metabolism, Health and Disease - A Review. Part 2: Fatty Acid Physiological Roles and Applications in Human Health and Disease

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