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https://www.readbyqxmd.com/read/28087575/treating-inflammation-and-infection-in-the-21st-century-new-hints-from-decoding-resolution-mediators-and-mechanisms
#1
REVIEW
Charles N Serhan
Practitioners of ancient societies from the time of Hippocrates and earlier recognized and treated the signs of inflammation, heat, redness, swelling, and pain with agents that block or inhibit proinflammatory chemical mediators. More selective drugs are available today, but this therapeutic concept has not changed. Because the acute inflammatory response is host protective to contain foreign invaders, much of today's pharmacopeia can cause serious unwanted side effects, such as immune suppression. Uncontrolled inflammation is now considered pathophysiologic and is associated with many widely occurring diseases such as cardiovascular disease, neurodegenerative diseases, diabetes, obesity, and asthma, as well as classic inflammatory diseases (e...
January 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28087294/bioactive-metabolites-of-docosahexaenoic-acid
#2
REVIEW
Ondrej Kuda
Docosahexaenoic acid (DHA) is an essential fatty acid that is recognized as a beneficial dietary constituent and as a source of the anti-inflammatory specialized proresolving mediators (SPM): resolvins, protectins and maresins. Apart from SPMs, other metabolites of DHA also exert potent biological effects. This article summarizes current knowledge on the metabolic pathways involved in generation of DHA metabolites. Over 70 biologically active metabolites have been described, but are often discussed separately within specific research areas...
January 10, 2017: Biochimie
https://www.readbyqxmd.com/read/28079976/maresin-1-induces-a-novel-pro-resolving-phenotype-in-human-platelets
#3
Katie L Lannan, Sherry L Spinelli, Neil Blumberg, Richard P Phipps
BACKGROUND: Antiplatelet therapy is a cornerstone of modern medical practice and is routinely employed to reduce the likelihood of myocardial infarction, thrombosis, and stroke. However, current antiplatelet therapies, such as aspirin, often have adverse side effects, including increased risk of bleeding, and some patients are relatively "aspirin-resistant". Platelets are intimately involved in hemostasis and inflammation, and clinical consequences are associated with excessive or insufficient platelet activation...
January 12, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28002074/resolving-inflammation-by-using-nutrition-therapy-roles-for-specialized-proresolving-mediators
#4
Lucy V Norling, Lucy Ly, Jesmond Dalli
PURPOSE OF REVIEW: Inflammation is a unifying component of many of the diseases that afflict Western civilizations. Nutrition therapy and, in particular, essential fatty acid supplementation is one of the approaches that is currently in use for the treatment and management of many inflammatory conditions. The purpose of the present review is to discuss the recent literature in light of the discovery that essential fatty acids are converted by the body to a novel genus of lipid mediators, termed specialized proresolving mediators (SPMs)...
December 20, 2016: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/27877134/modulation-of-the-activities-of-neuronal-ion-channels-by-fatty-acid-derived-pro-resolvents
#5
REVIEW
Geunyeol Choi, Sun Wook Hwang
Progress of inflammation depends on the balance between two biological mechanisms: pro-inflammatory and pro-resolving processes. Many extracellular and intracellular molecular components including cytokines, growth factors, steroids, neurotransmitters, and lipidergic mediators and their receptors contribute to the two processes, generated from cellular participants during inflammation. Fatty acid-derived mediators are crucial in directing the inflammatory phase and orchestrating heterogeneous reactions of participants such as inflamed cells, innate immune cells, vascular components, innervating neurons, etc...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27799313/identification-and-actions-of-the-maresin-1-metabolome-in-infectious-inflammation
#6
Romain A Colas, Jesmond Dalli, Nan Chiang, Iliyan Vlasakov, Julia M Sanger, Ian R Riley, Charles N Serhan
Maresin 1 (MaR1) is an immunoresolvent that governs resolution of acute inflammation, and its local metabolism in the context of infectious inflammation is of interest. In this study, we investigated the MaR1 metabolome in infectious exudates and its bioactions in regulating leukocyte responses in the context of bacterial infection. In Escherichia coli infectious exudates, MaR1 was temporally regulated with maximal levels at 4 h (2.2 ± 0.4 pg/lavage). In these exudates we also identified two novel products, and their structure elucidation gave 22-hydroxy-MaR1 and 14-oxo-MaR1...
December 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27791009/maresin-conjugates-in-tissue-regeneration-biosynthesis-enzymes-in-human-macrophages
#7
Jesmond Dalli, Iliyan Vlasakov, Ian R Riley, Ana R Rodriguez, Bernd W Spur, Nicos A Petasis, Nan Chiang, Charles N Serhan
Macrophages are central in coordinating immune responses, tissue repair, and regeneration, with different subtypes being associated with inflammation-initiating and proresolving actions. We recently identified a family of macrophage-derived proresolving and tissue regenerative molecules coined maresin conjugates in tissue regeneration (MCTR). Herein, using lipid mediator profiling we identified MCTR in human serum, lymph nodes, and plasma and investigated MCTR biosynthetic pathways in human macrophages. With human recombinant enzymes, primary cells, and enantiomerically pure compounds we found that the synthetic maresin epoxide intermediate 13S,14S-eMaR (13S,14S-epoxy- 4Z,7Z,9E,11E,16Z,19Z-docosahexaenoic acid) was converted to MCTR1 (13R-glutathionyl, 14S-hydroxy-4Z,7Z,9E,11E,13R,14S,16Z,19Z-docosahexaenoic acid) by LTC4S and GSTM4...
October 25, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27647830/signaling-and-immunoresolving-actions-of-resolvin-d1-in-inflamed-human-visceral-adipose-tissue
#8
Esther Titos, Bibiana Rius, Cristina López-Vicario, José Alcaraz-Quiles, Verónica García-Alonso, Aritz Lopategi, Jesmond Dalli, Juan José Lozano, Vicente Arroyo, Salvadora Delgado, Charles N Serhan, Joan Clària
Persistent activation of the innate immune system greatly influences the risk for developing metabolic complications associated with obesity. In this study, we explored the therapeutic potential of the specialized proresolving mediator (SPM) resolvin D1 (RvD1) to actively promote the resolution of inflammation in human visceral adipose tissue from obese (Ob) patients. Using liquid chromatography-tandem mass spectrometry-based metabololipidomic analysis, we identified unbalanced production of SPMs (i.e., D- and E-series resolvins, protectin D1, maresin 1, and lipoxins) with respect to inflammatory lipid mediators (i...
October 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27613620/maresin-1-maintains-the-permeability-of-lung-epithelial-cells-in-vitro-and-in-vivo
#9
Lin Chen, Hong Liu, Yaxin Wang, Haifa Xia, Jie Gong, Bo Li, Shanglong Yao, You Shang
Previous reports showed that Maresin 1 (MaR1) possessed organ protection effects and could attenuate acute lung injury. Here, we aim to figure out whether MaR1 can maintain the permeability of lung epithelial cells by regulating the expression of tight junction protein during lung injury. Monolayer of murine lung epithelial cells was stimulated by lipopolysaccharide (LPS) with or without MaR1 and the permeability was evaluated. The expression of Claudin-1 and ZO-1 in lung epithelial cells was analyzed by immunofluorescence staining and western blotting...
December 2016: Inflammation
https://www.readbyqxmd.com/read/27573698/endogenously-synthesized-n-3-fatty-acids-in-fat-1-transgenic-mice-prevent-melanoma-progression-by-increasing-e-cadherin-expression-and-inhibiting-%C3%AE-catenin-signaling
#10
Xuan Yin, Xiong-Wei Yu, Pan Zhu, Yuan-Ming Zhang, Xiao-Hong Zhang, Feng Wang, Jin-Jie Zhang, Wang Yan, Yang Xi, Jian-Bo Wan, Jing-Xuan Kang, Zu-Quan Zou, Shi-Zhong Bu
Malignant melanoma is the most lethal form of skin cancer. Although preclinical studies have shown that n-3 polyunsaturated fatty acids (PUFAs) are beneficial for prevention of melanoma, the molecular mechanisms underlying the protective effects of n‑3 PUFAs on melanoma remain largely unknown. In the present study, endogenously increased levels of n-3 PUFAs in the tumor tissues of omega‑3 fatty acid desaturase (fat‑1) transgenic mice was associated with a reduction in the growth rate of melanoma xenografts...
October 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27559094/proresolving-lipid-mediators-resolvin-d1-resolvin-d2-and-maresin-1-are-critical-in-modulating-t-cell-responses
#11
Valerio Chiurchiù, Alessandro Leuti, Jesmond Dalli, Anders Jacobsson, Luca Battistini, Mauro Maccarrone, Charles N Serhan
Resolution of inflammation is a finely regulated process mediated by specialized proresolving lipid mediators (SPMs), including docosahexaenoic acid (DHA)-derived resolvins and maresins. The immunomodulatory role of SPMs in adaptive immune cells is of interest. We report that D-series resolvins (resolvin D1 and resolvin D2) and maresin 1 modulate adaptive immune responses in human peripheral blood lymphocytes. These lipid mediators reduce cytokine production by activated CD8(+) T cells and CD4(+) T helper 1 (TH1) and TH17 cells but do not modulate T cell inhibitory receptors or abrogate their capacity to proliferate...
August 24, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27531933/resolving-lipid-mediators-maresin-1-and-resolvin-d2-prevent-atheroprogression-in-mice
#12
Joana R Viola, Patricia Lemnitzer, Yvonne Jansen, Gergely Csaba, Carla Winter, Carlos Neideck, Carlos Silvestre-Roig, Gunnar Dittmar, Yvonne Döring, Maik Drechsler, Christian Weber, Ralf Zimmer, Nicolas Cenac, Oliver Soehnlein
RATIONALE: Atheroprogression is a consequence of nonresolved inflammation, and currently a comprehensive overview of the mechanisms preventing resolution is missing. However, in acute inflammation, resolution is known to be orchestrated by a switch from inflammatory to resolving lipid mediators. Therefore, we hypothesized that lesional lipid mediator imbalance favors atheroprogression. OBJECTIVE: To understand the lipid mediator balance during atheroprogression and to establish an interventional strategy based on the delivery of resolving lipid mediators...
October 14, 2016: Circulation Research
https://www.readbyqxmd.com/read/27525060/selective-identification-of-specialized-pro-resolving-lipid-mediators-from-their-biosynthetic-double-di-oxygenation-isomers
#13
Trond V Hansen, Jesmond Dalli, Charles N Serhan
The n-3 polyunsaturated fatty acids are substrates for lipoxygenases and cyclooxygenases. During inflammatory processes, these enzymes form several distinct families of oxygenated polyunsaturated fatty acids coined specialized pro-resolving lipid mediators. Structural elucidation of these natural products using LC-MS/MS based metabololipidomics with the pico- to nanogram amounts of biosynthetic material available have been performed. The specialized pro-resolving lipid mediators display stereospecific and potent anti-inflammatory and pro-resolving actions...
2016: RSC Advances
https://www.readbyqxmd.com/read/27461565/divergent-shifts-in-lipid-mediator-profile-following-supplementation-with-n-3-docosapentaenoic-acid-and-eicosapentaenoic-acid
#14
James F Markworth, Gunveen Kaur, Eliza G Miller, Amy E Larsen, Andrew J Sinclair, Krishna Rao Maddipati, David Cameron-Smith
In contrast to the well-characterized effects of specialized proresolving lipid mediators (SPMs) derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), little is known about the metabolic fate of the intermediary long-chain (LC) n-3 polyunsaturated fatty acid (PUFA) docosapentaenoic acid (DPA). In this double blind crossover study, shifts in circulating levels of n-3 and n-6 PUFA-derived bioactive lipid mediators were quantified by an unbiased liquid chromatography-tandem mass spectrometry lipidomic approach...
November 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27422370/cyclopentenone-containing-oxidized-phospholipids-and-their-isoprostanes-as-pro-resolving-mediators-of-inflammation
#15
Olivier Friedli, Stefan Freigang
Inflammation represents a powerful innate immune response that defends tissue homeostasis. However, the appropriate termination of inflammatory processes is essential to prevent the development of chronic inflammatory disorders. The resolution of inflammation is actively induced by specialized pro-resolving lipid mediators, which include eicosanoids, resolvins, protectins and maresins. The responsible pro-resolution pathways have emerged as promising targets for anti-inflammatory therapies since they mitigate excessive inflammation without compromising the anti-microbial defenses of the host...
July 12, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27398158/maresin-1-ameliorates-iron-deficient-anemia-in-il-10-mice-with-spontaneous-colitis-by-the-inhibition-of-hepcidin-expression-though-the-il-6-stat3-pathway
#16
Honggang Wang, Peiliang Shi, Chuanjiang Huang, Qinghong Liu
BACKGROUND: Approximately 50% of patients with inflammatory bowel disease (IBD) suffer from anemia, which is prevalently caused by iron deficiency. Maresin 1 (MaR1) is a novel docosahexaenoic acid-derived pro-resolving agent that promotes the resolution of inflammation. The aim of the present study was to investigate the therapeutic effects of MaR1 on iron-deficient anemia in IL-10 knockout (IL-10(-/-)) mice with spontaneous chronic colitis. METHODS: IL-10(-/-) mice of 16 weeks of age with established colitis were used for the experiments with MaR1 treatment for 2 weeks...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27337457/macrophage-proresolving-mediators-the-when-and-where
#17
Jesmond Dalli, Charles Serhan
Macrophages and neutrophils orchestrate acute inflammation and host defense as well as the resolution phase and return to homeostasis. In this article, we review the contribution of macrophages to local lipid mediator (LM) levels and the regulation of macrophage LM profiles by polymorphonuclear neutrophils and neutrophil-derived microparticles. We carried out LM metabololipidomics, profiling distinct phagocytes: neutrophils (PMNs), apoptotic PMNs, and macrophages. Efferocytosis increased specialized proresolving mediator (SPM) biosynthesis, including resolvin D1 (RvD1), RvD2, and RvE2, which were further elevated by PMN microparticles...
June 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/27320930/potential-of-specialized-pro-resolving-lipid-mediators-against-rheumatic-diseases
#18
Kosaku Murakami
  While arachidonic acid (AA), which is classified into n-6 polyunsaturated fatty acid (PUFA), has been mainly recognized as a substrate of pro-inflammatory mediators, eicosapentaenoic acid or docosahexaenoic acid, which are classified into n-3 PUFA, is currently identified as substrates of mediators inducing resolution of inflammation, namely pro-resolving mediators (SPM). As with any other pathological conditions, it is gradually elucidated that SPMs contributes a certain effect on joint inflammation. In osteoarthritis (OA), Lipid fractions extracted from adipocytes, especially in infrapatellar fat pad rather than subcutaneous tissue induce T cell skewing for producing IFN-γ or decrease the production of IL-12p40 from macrophages...
2016: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/27297719/combinations-of-distinct-long-chain-polyunsaturated-fatty-acid-species-for-improved-dietary-treatment-against-allergic-bronchial-asthma
#19
Christopher Beermann, Sandy Neumann, Daniela Fußbroich, Stefan Zielen, Ralf Schubert
Allergic bronchial asthma is a chronic inflammatory disease of the airways with an increasing incidence in Western societies. Exposure to allergens provokes recurrent attacks of breathlessness, airway hyperreactivity, wheezing, and coughing. For the early phase and milder forms of allergic asthma, dietary supplementation with long-chain polyunsaturated fatty acids (LCPUFA), predominantly fish oil-associated eicosapentaenoic (C20:5 ω-3) and docosahexaenoic acid (C22:6 ω-3), and distinct crop oil-derived fatty acids might provide a sustainable treatment strategy, as discussed in several studies...
November 2016: Nutrition
https://www.readbyqxmd.com/read/27033423/specialised-pro-resolving-mediators-of-inflammation-in-inflammatory-arthritis
#20
Anne E Barden, Mahin Moghaddami, Emilie Mas, Michael Phillips, Leslie G Cleland, Trevor A Mori
INTRODUCTION: Specialised pro-resolving mediators (SPM) are derived from n-3 long chain polyunsaturated fatty acids (n-3FA). They promote resolution of inflammation and may contribute to the beneficial effects of n-3FA in patients with arthritis. This study compared SPM in knee effusions and plasma of patients with arthritis taking n-3FA, and plasma of healthy volunteers taking n-3FA. METHODS: Thirty six patients taking n-3FA undergoing arthrocentesis for an inflammatory knee effusion and 36 healthy volunteers who had taken n-3FA (2...
April 2016: Prostaglandins, Leukotrienes, and Essential Fatty Acids
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