Anti-inflammatory lipid mediators and insights into the resolution of inflammation

IntroductionBronchiectasis is characterised by excessive neutrophilic inflammation. Lipid mediators such as prostaglandins and leukotrienes have crucial roles in the inflammatory response. Further characterisation of these lipids and understanding the interplay of anti-inflammatory and proinflammatory lipid mediators could lead to the development of novel anti-inflammatory therapies for bronchiectasis.AimThe aim of our study was to characterise the lipids obtained from serum and airways in patients with bronchiectasis in the stable state.MethodsSix healthy volunteers, 10 patients with mild bronchiectasis, 15 with moderate bronchiectasis and 9 with severe bronchiectasis were recruited. All participants had 60 mL of blood taken and underwent a bronchoscopy while in the stable state. Lipidomics was done on serum and bronchoalveolar lavage fluid (BALF).ResultsIn the stable state, in serum there were significantly higher levels of prostaglandin E2 (PGE2), 15-hydroxyeicosatetranoic acid (15-HETE) and leukotriene B4 (LTB4) in patients with moderate–severe disease compared with healthy volunteers. There was a significantly lower level of lipoxin A4 (LXA4) in severe bronchiectasis.In BALF, there were significantly higher levels of PGE2, 5-HETE, 15-HETE, 9-hydroxyoctadecadienoic acid and LTB4 in moderate–severe patients compared with healthy volunteers.In the stable state, there was a negative correlation of PGE2 and LTB4 with % predicted forced expiratory volume in 1 s and a positive correlation with antibiotic courses.LXA4 improved blood and airway neutrophil phagocytosis and bacterial killing in patients with bronchiectasis. Additionally LXA4 reduced neutrophil activation and degranulation.ConclusionThere is a dysregulation of lipid mediators in bronchiectasis with excess proinflammatory lipids. LXA4 improves the function of reprogrammed neutrophils. The therapeutic efficacy of LXA4 in bronchiectasis warrants further studies.

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Therapeutic Applicability of Anti-Inflammatory and Proresolving Polyunsaturated Fatty Acid-Derived Lipid Mediators

The Scientific World JOURNAL ◽

10.1100/tsw.2010.57 ◽

2010 ◽

Vol 10 ◽

pp. 676-712 ◽

Cited By ~ 20

Author(s):

Gerard L. Bannenberg

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Polyunsaturated Fatty Acids ◽

Host Defense ◽

Inflammatory Disease ◽

Lipid Mediators ◽

Molecular Pathways ◽

Tissue Protection ◽

Anti Inflammatory ◽

Long Chain

The enzymatic oxygenation of polyunsaturated fatty acids by lipoxygenases and cyclo-oxygenases is a resourceful mode of formation of specific autacoids that regulate the extent and pace of the inflammatory response. Arachidonate-derived eicosanoids, such as lipoxin A4, prostaglandin (PG)D2, PGF2α, PGE2, and PGD2-derived cyclopentenones exert specific roles in counter-regulating inflammation and turning on resolution. Recently recognized classes of autacoids derived from long-chain ω-3 polyunsaturated fatty acids, the E- and D-series resolvins, protectin D1, and maresin 1, act as specialized mediators to dampen inflammation actively, afford tissue protection, stimulate host defense, and activate resolution. It is held that counter-regulatory lipid mediators and the specific molecular pathways activated by such endogenous agonists may be suitable for pharmacological use in the treatment of inflammatory disease. The anti-inflammatory drug aspirin is a striking example of a drug that is able to act in such a manner, namely through triggering the formation of 15-epi-lipoxin A4and aspirin-triggered resolvins. Different aspects of the therapeutic applicability of lipid mediators have been addressed here, and indicate that the development of innovative pharmacotherapy based on anti-inflammatory and proresolution lipid mediators presents novel prospects for the treatment of inflammatory disease.

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New Perspectives on Aspirin and the Endogenous Control of Acute Inflammatory Resolution

The Scientific World JOURNAL ◽

10.1100/tsw.2006.192 ◽

2006 ◽

Vol 6 ◽

pp. 1048-1065 ◽

Cited By ~ 16

Author(s):

Thea Morris ◽

Melanie Stables ◽

Derek W. Gilroy

Keyword(s):

Mode Of Action ◽

Acute Inflammation ◽

Lipid Mediators ◽

The Other ◽

Endogenous Control ◽

Protective Properties ◽

Traditional Mode ◽

Inflammatory Drugs ◽

Cox 2 ◽

Anti Inflammatory

Aspirin is unique among the nonsteroidal anti-inflammatory drugs in that it has both anti-inflammatory as well as cardio-protective properties. The cardio-protective properties arise form its judicious inhibition of platelet-derived thromboxane A2over prostacyclin, while its anti-inflammatory effects of aspirin stem from its well-established inhibition of prostaglandin (PG) synthesis within inflamed tissues. Thus aspirin and the other NSAIDs have popularised the notion of inhibiting PG biosynthesis as a common anti-inflammatory strategy based on the erroneous premise that all eicosanoids are generally detrimental to inflammation. However, our fascination with aspirin has shown a more affable side to lipid mediators based on our increasing interest in the endogenous control of acute inflammation and in factors that mediate its resolution. Epi-lipoxins (epi-LXs), for instance, are produced from aspirins acetylation of inducible cyclooxygenase 2 (COX-2) and together with Resolvins represent an increasingly important family of immuno-regulatory and potentially cardio-protective lipid mediators. Aspirin is beginning to teach us what nature knew all along that not all lipid mediators are bad. It seems that while some eicosanoids are pathogenic in a variety of diseases, others are unarguable protective. In this review we will re-count aspirins colorful history, discuss its traditional mode of action and the controversies associated therewith, as well as highlight some of the new pathways in inflammation and the cardiovascular systems that aspirin has recently revealed.

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Roles of Specialized Pro-Resolving Lipid Mediators in Autophagy and Inflammation

International Journal of Molecular Sciences ◽

10.3390/ijms21186637 ◽

2020 ◽

Vol 21 (18) ◽

pp. 6637 ◽

Cited By ~ 1

Author(s):

Antonio Recchiuti ◽

Elisa Isopi ◽

Mario Romano ◽

Domenico Mattoscio

Keyword(s):

Inflammatory Response ◽

Cytokine Production ◽

Lipid Mediators ◽

Tissue Homeostasis ◽

Leukocyte Infiltration ◽

Catabolic Pathway ◽

Resolution Of Inflammation ◽

Endogenous Lipid ◽

Inflammation Resolution ◽

Cellular Components

Autophagy is a catabolic pathway that accounts for degradation and recycling of cellular components to extend cell survival under stress conditions. In addition to this prominent role, recent evidence indicates that autophagy is crucially involved in the regulation of the inflammatory response, a tightly controlled process aimed at clearing the inflammatory stimulus and restoring tissue homeostasis. To be efficient and beneficial to the host, inflammation should be controlled by a resolution program, since uncontrolled inflammation is the underlying cause of many pathologies. Resolution of inflammation is an active process mediated by a variety of mediators, including the so-called specialized pro-resolving lipid mediators (SPMs), a family of endogenous lipid autacoids known to regulate leukocyte infiltration and activities, and counterbalance cytokine production. Recently, regulation of autophagic mechanisms by these mediators has emerged, uncovering unappreciated connections between inflammation resolution and autophagy. Here, we summarize mechanisms of autophagy and resolution, focusing on the contribution of autophagy in sustaining paradigmatic examples of chronic inflammatory disorders. Then, we discuss the evidence that SPMs can restore dysregulated autophagy, hypothesizing that resolution of inflammation could represent an innovative approach to modulate autophagy and its impact on the inflammatory response.

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Intravenous fish oil lipid emulsion promotes a shift toward anti-inflammatory proresolving lipid mediators

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00106.2013 ◽

2013 ◽

Vol 305 (11) ◽

pp. G818-G828 ◽

Cited By ~ 30

Author(s):

Brian T. Kalish ◽

Hau D. Le ◽

Jonathan M. Fitzgerald ◽

Samantha Wang ◽

Kyle Seamon ◽

...

Keyword(s):

Liver Disease ◽

Fish Oil ◽

Lipid Emulsion ◽

Lipid Mediators ◽

Lipid Emulsions ◽

Serum Samples ◽

Human Infants ◽

Life Threatening ◽

Small Cohort ◽

Anti Inflammatory

Parenteral nutrition (PN)-associated liver disease (PNALD) is a life-threatening complication of the administration of PN. The development of PNALD may be partly due to the composition of the lipid emulsion administered with PN: soybean oil-based lipid emulsions (SOLE) are associated with liver disease, while fish oil-based lipid emulsions (FOLE) are associated with prevention and improvement of liver disease. The objective of this study was to determine how the choice of lipid emulsion modified the production of bioactive lipid mediators (LMs). We utilized a mouse model of steatosis to study the differential effect of FOLE and SOLE. We subsequently validated these results in serum samples from a small cohort of human infants transitioning from SOLE to FOLE. In mice, FOLE was associated with production of anti-inflammatory, proresolving LMs; SOLE was associated with increased production of inflammatory LMs. In human infants, the transition from SOLE to FOLE was associated with a shift toward a proresolving lipidome. Together, these results demonstrate that the composition of the lipid emulsion directly modifies inflammatory homeostasis.

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New endogenous anti-inflammatory and proresolving lipid mediators: implications for rheumatic diseases

Nature Clinical Practice Rheumatology ◽

10.1038/ncprheum0616 ◽

2007 ◽

Vol 3 (10) ◽

pp. 570-579 ◽

Cited By ~ 52

Author(s):

Stephanie Yacoubian ◽

Charles N Serhan

Keyword(s):

Rheumatic Diseases ◽

Lipid Mediators ◽

Anti Inflammatory

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Differential effects of EPA and DHA on plasma and adipose tissue lipid mediators: the ComparED study

Proceedings of The Nutrition Society ◽

10.1017/s0029665120001123 ◽

2020 ◽

Vol 79 (OCE2) ◽

Author(s):

Cécile Vors ◽

Fabiana Piscitelli ◽

Roberta Verde ◽

Sofia Laforest ◽

Janie Allaire ◽

...

Keyword(s):

Adipose Tissue ◽

Plasma Levels ◽

Corn Oil ◽

Lipid Mediators ◽

High Dose ◽

Low Grade ◽

Double Blind ◽

Epa And Dha ◽

Anti Inflammatory ◽

The Individual

AbstractOxylipins and endocannabinoids (eCBs) both belong to superclasses of lipid mediators with potent inflammation modulatory activities. The adipose tissue (AT) plays a key role in metabolic syndrome-related inflammation, via altered adipocyte physiology, infiltrated macrophages and altered profile of eCBs. We previously reported that DHA is more potent than EPA at modulating systemic inflammation, but the underlying mechanisms remain unclear. The objective of this study was to compare the individual effect of high-dose DHA and of EPA on circulating lipid mediators, i.e. plasma oxylipins and eCBs, and AT-related inflammation. In a randomized double-blind crossover trial, 154 volunteers with abdominal obesity and low-grade inflammation were subjected to three 10-wk supplementation phases: 1- EPA (2.7 g/d); 2- DHA (2.7 g/d); 3- corn oil (control), each separated by a 9-wk washout. Supplements were provided as re-esterified triacylglycerols. Profiling of plasma oxylipins and eCBs was performed on 58 subjects after each phase. Abdominal subcutaneous AT biopsies were also obtained from 13 individuals after each phase. Plasma DHA-, EPA-, arachidonic acid-derived oxylipins were analyzed by LC-MS. eCBs and some of their bioactive congeners were analyzed in plasma and AT by LC-APCI-MS. Adipocyte diameter was determined by histological analysis and AT macrophage infiltration was quantified by double immunofluorescence. Compared with EPA, DHA increased plasma levels of hydroxy-docosahexaenoic acids (7-, 11-, 14-, 4-, 17-HDOHE; P < 0.0001) and palmitoylethanolamide (PEA; P = 0.04). Compared with DHA, EPA led to higher plasma level of hydroxy-eicosapentaenoic acids (12-, 15-, 5-HEPE; P < 0.0001). In the AT, EPA increased the level of oleoylethanolamide (OEA; P = 0.01) compared with DHA, but no other difference was observed between treatments in adipose eCBs and eCB-related lipids. DHA and EPA did not differentially modify adipocyte size distributions (P > 0.50) and proportions of M1-type and M2-type macrophages (P > 0.30). In conclusion, increased plasma levels of anti-inflammatory DHA-derived oxylipins and plasma PEA may be responsible, at least to some extent, for the more potent anti-inflammatory effects of DHA compared with EPA observed in the ComparED study. Conversely, subcutaneous AT does not seem to be involved in explaining such differences between EPA and DHA.

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