Lipid Mediators in the Resolution of Inflammation

Serhan, Charles N.; Chiang, Nan; Dalli, Jesmond; Levy, Bruce D.

doi:10.1101/cshperspect.a016311

Cited by 443 publications

(373 citation statements)

References 140 publications

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“…As discussed, LTB4 is a neutrophil chemoattractant, but after lipid-mediator class switching pro-inflammatory lipid mediator production pathways are altered to instead produce pro-resolution mediators such as lipoxin A4 (LXA4) 116,117 . Other pro-resolution lipid mediators include resolvins and protectins and stop the influx of new neutrophils 118 .…”

Section: Reverse Migration Of Neutrophilsmentioning

confidence: 99%

Neutrophil migration in infection and wound repair: going forward in reverse

2016

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Neutrophil migration and its role during inflammation has been the focus of increased interest in the past decade. Advances in live imaging and the use of new model systems have helped to uncover the behaviour of neutrophils in injured and infected tissues. Although neutrophils were considered to be short-lived effector cells that undergo apoptosis in damaged tissues, recent evidence suggests that neutrophil behaviour is more complex and, in some settings, neutrophils might leave sites of tissue injury and migrate back into the vasculature. The role of reverse migration and its contribution to resolution of inflammation remains unclear. Here, we discuss the different cues within tissues that mediate neutrophil forward and reverse migration in response to injury or infection, and the implications of these mechanisms to human disease.

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Section: Reverse Migration Of Neutrophilsmentioning

confidence: 99%

Neutrophil migration in infection and wound repair: going forward in reverse

2016

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“…A simplistic view is that n-3 PUFAs form the basis of lipid derivatives with anti-inflammatory properties, whereas n-6 PUFAs are the precursors of proinflammatory mediators, and stimulate the production and activity of proinflammatory factors such as cytokines (Farooqui et al, 2007;Orr et al, 2013;Serhan et al, 2014). As a result, we have previously demonstrated that low dietary intake of n-3 PUFAs promotes neuroinflammatory responses through the regulation of microglial cells activity and polarization toward a pro-inflammatory phenotype, while n-3 PUFA dietary supplementation is rather anti-inflammatory (De SmedtPeyrusse et al, 2008;Mingam et al, 2008;Labrousse et al, 2012;Madore et al, 2014;Delpech et al, 2015a).…”

Section: Introductionmentioning

confidence: 99%

Dietary n-3 PUFAs Deficiency Increases Vulnerability to Inflammation-Induced Spatial Memory Impairment

Delpech

Thomazeau

Madore

et al. 2015

Neuropsychopharmacol

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Dietary n-3 polyunsaturated fatty acids (PUFAs) are critical components of inflammatory response and memory impairment. However, the mechanisms underlying the sensitizing effects of low n-3 PUFAs in the brain for the development of memory impairment following inflammation are still poorly understood. In this study, we examined how a 2-month n-3 PUFAs deficiency from pre-puberty to adulthood could increase vulnerability to the effect of inflammatory event on spatial memory in mice. Mice were given diets balanced or deficient in n-3 PUFAs for a 2-month period starting at post-natal day 21, followed by a peripheral administration of lipopolysaccharide (LPS), a bacterial endotoxin, at adulthood. We first showed that spatial memory performance was altered after LPS challenge only in n-3 PUFA-deficient mice that displayed lower n-3/n-6 PUFA ratio in the hippocampus. Importantly, long-term depression (LTD), but not long-term potentiation (LTP) was impaired in the hippocampus of LPS-treated n-3 PUFA-deficient mice. Proinflammatory cytokine levels were increased in the plasma of both n-3 PUFA-deficient and n-3 PUFA-balanced mice. However, only n-3 PUFA-balanced mice showed an increase in cytokine expression in the hippocampus in response to LPS. In addition, n-3 PUFA-deficient mice displayed higher glucocorticoid levels in response to LPS as compared with n-3 PUFA-balanced mice. These results indicate a role for n-3 PUFA imbalance in the sensitization of the hippocampal synaptic plasticity to inflammatory stimuli, which is likely to contribute to spatial memory impairment.

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“…SPM are produced via the actions of specific lipoxygenases on different substrates, including arachidonic acid-derived lipoxins (LXA 4 and LXB 4 ), eicosapentaenoic acid (EPA)-derived E-series resolvins (RvE1-3), docosahexaenoic acid (DHA)-derived D-series resolvins (RvD1-6), maresins and protectins (10, 12–24). Activation of resolution signals occurs when specific SPMs interact with cognate G-protein coupled receptors (GPCRs) present on the cell surface (25, 26). Lipoxin A 4 (LXA 4 ) binds its receptor, ALX/FPR2, transducing signals with potent actions in experimentally induced animal disease models (27).…”

Section: Introductionmentioning

confidence: 99%

Neutrophil Resolvin E1 Receptor Expression and Function in Type 2 Diabetes

Freire

Dalli

Serhan

et al. 2017

The Journal of Immunology

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Unresolved inflammation is key in linking metabolic dysregulation and the immune system in type 2 diabetes. Successful regulation of acute inflammation requires biosynthesis of specialized pro-resolving lipid mediators, such as resolvin E1 (RvE1), and activation of cognate g-protein coupled receptors (GPCR). RvE1 binds to BLT-1 on neutrophils and ERV-1/ChemR23 on monocyte/macrophages. We show novel actions of RvE1 and expression patterns of neutrophil receptors in type 2 diabetes. Neutrophils from healthy subjects express functional BLT-1, low levels of minimally functional ERV-1 and inversed co-expression in type2 diabetes. Stimulation with TNFα or LPS increased expression of ERV-1 by healthy and diabetic neutrophils. RvE1 has counteracted LPS and TNFα induction of ERV1 overexpression and diabetic overexpression activating phagocytosis and resolution signals. Functional ERV-1 was determined by phosphorylation of the signaling protein, ribosomal S6 (rS6). Receptor antagonism experiments revealed that the phospho-rS6 increase was mediated by BLT-1 in healthy subject neutrophils and ERV1 in diabetes. Metalolipidomics reveal a pro-inflammatory profile in diabetic serum. Cell phagocytosis is impaired in type 2 diabetes and requires RvE1 for activation. The dose of RvE1 required to activate resolution signals in type 2 diabetic neutrophils was significantly higher than healthy controls. RvE1 rescued aberrant neutrophil receptor profile and, following a therapeutic dosage, activates phagocytosis and resolution in type 2 diabetes. These findings reveal the importance of resolution receptors in health, disease and dysregulation of inflammation in type 2 diabetes.

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Lipid Mediators in the Resolution of Inflammation

Cited by 443 publications

References 140 publications

Neutrophil migration in infection and wound repair: going forward in reverse

Neutrophil migration in infection and wound repair: going forward in reverse

Dietary n-3 PUFAs Deficiency Increases Vulnerability to Inflammation-Induced Spatial Memory Impairment

Neutrophil Resolvin E1 Receptor Expression and Function in Type 2 Diabetes

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