Resolvins and Protectins in Inflammation Resolution

Serhan, Charles N.; Petasis, Nicos A.

doi:10.1021/cr100396c

Cited by 853 publications

(987 citation statements)

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“…7,12,28,29 The 17R epimer or AT form can be generated endogenously by aspirin-acetylated cyclooxygenase-2 performing the initial conversion of DHA; however, aspirin-independent biosynthesis of ATRvD3 also occurs in mammalian tissues. 7,12,28 Recent work established a method for total organic synthesis of RvD3 and AT-RvD3 that enabled elucidation of the stereochemistry of these mediators. 12,29 In addition to peritonitis, 12 RvD3 biosynthesis also occurs after kidney ischemia and colitis.…”

Section: Discussionmentioning

confidence: 99%

Resolvin D3 and Aspirin-Triggered Resolvin D3 Are Protective for Injured Epithelia

Colby

Abdulnour

Sham

et al. 2016

The American Journal of Pathology

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Acute lung injury is a life-threatening condition caused by disruption of the alveolar-capillary barrier leading to edema, influx of inflammatory leukocytes, and impaired gas exchange. Specialized proresolving mediators biosynthesized from essential fatty acids, such as docosahexaenoic acid, have tissue protective effects in acute inflammation. Herein, we found that the docosahexaenoic acidederived mediator resolvin D3 (RvD3): 4S,11R,17S-trihydroxydocosa-5Z,7E,9E,13Z,15E,19Z-hexaenoic acid was present in uninjured lungs, and increased significantly 24 to 72 hours after hydrochloric acideinitiated injury. Because of its delayed enzymatic degradation, we used aspirin-triggered (AT)-RvD3: 4S,11R,17R-trihydroxydocosa-5Z,7E,9E,13Z,15E,19Z-hexaenoic acid, a 17R-epimer of RvD3, for in vivo experiments. Histopathological correlates of acid injury (alveolar wall thickening, edema, and leukocyte infiltration) were reduced in mice receiving AT-RvD3 1 hour after injury. AT-RvD3etreated mice had significantly reduced edema, as demonstrated by lower wet/dry weight ratios, increased epithelial sodium channel g expression, and more lymphatic vessel endothelial hyaluronan receptor 1-positive vascular endothelial growth factor receptor 3-positive lymphatic vessels. Evidence for counterregulation of NF-kB by RvD3 and AT-RvD3 was seen in vitro and by AT-RvD3 in vivo. Increases in lung epithelial cell proliferation and bronchoalveolar lavage fluid levels of keratinocyte growth factor were observed with AT-RvD3, which also promoted cutaneous re-epithelialization. Together, these data demonstrate protective actions of RvD3 and AT-RvD3 for injured mucosa that accelerated restoration of epithelial barrier and function. (Am J Pathol 2016 http://dx.doi.org/10.1016/j.ajpath.2016 Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are serious conditions characterized by loss of normal epithelial and endothelial barrier function, leading to pulmonary edema and infiltration of leukocytes culminating in significant impairments in gas exchange. 1 ARDS and its milder form, ALI, are serious conditions characterized by loss of normal epithelial and endothelial barrier function, leading to pulmonary edema and infiltration of leukocytes culminating in significant impairments in gas exchange. 1 ALI is a common condition, affecting approximately 200,000 patients a year in the United States alone. 2 Although our understanding of the pathophysiological changes associated with ALI/ARDS has improved since its original description, effective management of this condition still proves difficult, and mortality remains approximately 40%. 2 Aspiration pneumonia/pneumonitis is a common cause of ALI/ARDS characterized by direct damage to lung epithelia (because of the low pH of gastric contents) followed by extensive sloughing of the injured epithelial cells. 3 Despite significant damage to the epithelial barrier,

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Section: Discussionmentioning

confidence: 99%

Resolvin D3 and Aspirin-Triggered Resolvin D3 Are Protective for Injured Epithelia

Colby

Abdulnour

Sham

et al. 2016

The American Journal of Pathology

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“…However, there is considerable research showing a wide range of mechanisms potentially underpinning the effects of n-3 LC-PUFA on inflammatory responses and immune pathways (Chapkin et al, 2009;Calder, 2013). In particular in recent years, it has been established that the n-3 LC-PUFA, EPA and DHA, are also precursors of other COX-2 derived non-classical eicosanoid derivatives called resolvins, maresins and protectins, which are specialized pro-resolving mediators (PSM) that bring about resolution of the inflammatory response and a return to homeostasis (Serhan and Petasis, 2011;Weylandt et al, 2012). In addition, as ligands of various transcription factors, n-3 LC-PUFA and their derivatives can also have affects on expression of genes in inflammatory and immune pathways (Chapkin et al, 2009;Schmuth et al, 2014).…”

Section: Inflammatory Diseasementioning

confidence: 99%

Omega-3 long-chain polyunsaturated fatty acids and aquaculture in perspective

2015

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Abbreviations: ARA, arachidonic acid (20:4n-6); CVD, cardiovascular disease; DHA, docosahexaenoic acid (22:6n-3); DPA, docosapentaenoic acid (22:5n-3); EFA, essential fatty acid; Elovl, fatty acid elongase; EPA, eicosapentaenoic acid (20:5n-3); Fads, fatty acyl desaturase; FM, fishmeal; FO, fish oil; LC-PUFA, long-chain polyunsaturated fatty acids (≥ C20 ≥ 3 double bonds); LOA, linoleic acid (18:2n-6); LNA, linolenic acid (18:3n-3); PUFA, polyunsaturated fatty acid; TAG, triacylglycerol; VO, vegetable oil. ABSTRACTIn the 40 years since the essentiality of polyunsaturated fatty acids (PUFA) in fish was first established by determining quantitative requirements for 18:3n-3 and 18:2n-6 in rainbow trout, essential fatty acid (EFA) research has gone through distinct phases. For 20 years the focus was primarily on determining qualitative and quantitative EFA requirements of fish species. Nutritional and biochemical studies showed major differences between fish species based on whether C 18 PUFA or long-chain (LC)-PUFA were required to satisfy requirements. In contrast, in the last 20 years, research emphasis shifted to determining "optimal" levels of EFA to support growth of fish fed diets with increased lipid content and where growth expectations were much higher. This required greater knowledge of the roles and functions of EFA in metabolism and physiology, and how these impacted on fish health and disease. Requirement studies were more focused on early life stages, in particular larval marine fish, defining not only levels, but also balances between different EFA. Finally, a major driver in the last 10-15 years has been the unavoidable replacement of fish oil and fishmeal in feeds and the impacts that this can have on n-3 LC-PUFA contents of diets and farmed fish, and the human consumer. Thus, dietary n-3 in fish feeds can be defined by three levels.Firstly, the minimum level required to satisfy EFA requirements and thus prevent nutritional pathologies. This level is relatively small and easy to supply even with today's current high demand for fish oil. The second level is that required to sustain maximum growth and optimum health in fish being fed modern high-energy diets. The balance between different PUFA and LC-PUFA is important and defining them is more challenging, and so ideal levels and balances are still not well understood, particularly in relation to fish health. The third level is currently driving much research; how can we supply sufficient n-3 LC-PUFA to maintain the nutritional quality of farmed fish at the same level as 20 years ago, and similar or better than in wild fish? This level far exceeds the biological requirements of the fish itself and to satisfy it we require entirely new sources of n-3 LC-PUFA. We cannot rely on the finite and limited marine resources that we can sustainably harvest or 3 efficiently recycle. We need to produce n-3 LC-PUFA de novo and all possible options should be considered.Keywords: Fish oil; essential fatty acids; nutrition; health; metabolism; sustainability 4 Highl...

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“…Serhan et al (19) described the E-series resolvins derived from EPA, and D-series resolvins, protectins, neuroprotectins and maresins derived from DHA (66)(67)(68)(69) . These mediators acting via G-coupled protein receptors (70) have potent anti-inflammatory and pro-resolving actions (71,72) and increase with time during the inflammatory process (19,73) . Two series of resolvins and protectins have been identified: those derived via lipoxygenase metabolism of EPA and DHA, and a second series derived from aspirin-triggered cyclooxygenase-2 or cytochrome P450 metabolism of EPA and DHA.…”

Section: Effects On Inflammationmentioning

confidence: 99%

Dietary n-3 PUFA and CVD: a review of the evidence

Mori

2013

Proc. Nutr. Soc.

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Many clinical and epidemiological studies have shown that the polyunsaturated n-3 fatty acids EPA and DHA from fish and fish oils, provide cardiovascular protection, particularly in the setting of secondary prevention. n-3 Fatty acids beneficially influence a number of cardiometabolic risk factors including blood pressure, cardiac function, vascular reactivity and lipids, as well as having anti-platelet, anti-inflammatory and anti-oxidative actions. They do not appear to adversely interact with other medications such as statins and other lipid-lowering drugs or antihypertensive medications. n-3 Fatty acids have gained widespread usage by general practitioners and clinicians in a number of clinical settings such as pregnancy and infant development, secondary prevention in CHD patients, treatment of dyslipidaemias and haemodialysis patients. Small doses are achievable with consumption of two to three oily fish meals per week or via purified encapsulated preparations now readily available. n-3 Fatty acids, particularly when consumed as fish, should be considered an important component of a healthy diet. The present paper reviews the effects of n-3 fatty acids on cardiometabolic risk factors, concentrating particularly on the evidence from randomised controlled studies in human subjects.

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Resolvins and Protectins in Inflammation Resolution

Cited by 853 publications

References 163 publications

Resolvin D3 and Aspirin-Triggered Resolvin D3 Are Protective for Injured Epithelia

Resolvin D3 and Aspirin-Triggered Resolvin D3 Are Protective for Injured Epithelia

Omega-3 long-chain polyunsaturated fatty acids and aquaculture in perspective

Dietary n-3 PUFA and CVD: a review of the evidence

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