Dataset Information

Specialized pro-resolving lipid mediators in the inflammatory response: An update.

ABSTRACT: A new genus of specialized pro-resolving mediators (SPM) which include several families of distinct local mediators (lipoxins, resolvins, protectins, and maresins) are actively involved in the clearance and regulation of inflammatory exudates to permit restoration of tissue homeostasis. Classic lipid mediators that are temporally regulated are formed from arachidonic acid, and novel local mediators were uncovered that are biosynthesized from ?-3 poly-unsaturated fatty acids, such as eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid. The biosynthetic pathways for resolvins are constituted by fatty acid lipoxygenases and cyclooxygenase-2 via transcellular interactions established by innate immune effector cells which migrate from the vasculature to inflamed tissue sites. SPM provide local control over the execution of an inflammatory response towards resolution, and include recently recognized actions of SPM such as tissue protection and host defense. The structural families of the SPM do not resemble classic eicosanoids (PG or LT) and are novel structures that function uniquely via pro-resolving cellular and molecular targets. The extravasation of inflammatory cells expressing SPM biosynthetic routes are matched by the temporal provision of essential fatty acids from circulation needed as substrate for the formation of SPM. The present review provides an update and overview of the biosynthetic pathways and actions of SPM, and examines resolution as an integrated component of the inflammatory response and its return to homeostasis via biochemically active resolution mechanisms.

SUBMITTER: Bannenberg G

PROVIDER: S-EPMC2994245 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Specialized pro-resolving lipid mediators in the inflammatory response: An update.

Bannenberg Gerard G Serhan Charles N CN

Biochimica et biophysica acta 20100810 12

A new genus of specialized pro-resolving mediators (SPM) which include several families of distinct local mediators (lipoxins, resolvins, protectins, and maresins) are actively involved in the clearance and regulation of inflammatory exudates to permit restoration of tissue homeostasis. Classic lipid mediators that are temporally regulated are formed from arachidonic acid, and novel local mediators were uncovered that are biosynthesized from ω-3 poly-unsaturated fatty acids, such as eicosapentae ...[more]

PMID: 20708099

Similar Datasets

Project description:Diabetes and its associated chronic complications present a healthcare challenge on a global scale. Despite improvements in the management of chronic complications of the micro-/macro-vasculature, their growing prevalence and incidence highlights the scale of the problem. It is currently estimated that diabetes affects 425 million people globally and it is anticipated that this figure will rise by 2025 to 700 million people. The vascular complications of diabetes including diabetes-associated atherosclerosis and kidney disease present a particular challenge. Diabetes is the leading cause of end stage renal disease, reflecting fibrosis leading to organ failure. Moreover, diabetes associated states of inflammation, neo-vascularization, apoptosis and hypercoagulability contribute to also exacerbate atherosclerosis, from the metabolic syndrome to advanced disease, plaque rupture and coronary thrombosis. Current therapeutic interventions focus on regulating blood glucose, glomerular and peripheral hypertension and can at best slow the progression of diabetes complications. Recently advanced knowledge of the pathogenesis underlying diabetes and associated complications revealed common mechanisms, including the inflammatory response, insulin resistance and hyperglycemia. The major role that inflammation plays in many chronic diseases has led to the development of new strategies aiming to promote the restoration of homeostasis through the "resolution of inflammation." These strategies aim to mimic the spontaneous activities of the 'specialized pro-resolving mediators' (SPMs), including endogenous molecules and their synthetic mimetics. This review aims to discuss the effect of SPMs [with particular attention to lipoxins (LXs) and resolvins (Rvs)] on inflammatory responses in a series of experimental models, as well as evidence from human studies, in the context of cardio- and reno-vascular diabetic complications, with a brief mention to diabetic retinopathy (DR). These data collectively support the hypothesis that endogenously generated SPMs or synthetic mimetics of their activities may represent lead molecules in a new discipline, namely the 'resolution pharmacology,' offering hope for new therapeutic strategies to prevent and treat, specifically, diabetes-associated atherosclerosis, nephropathy and retinopathy.

Project description:BACKGROUND:N-3 polyunsaturated fatty acid (PUFA) supplementation has been associated with reduced mortality and inflammation in patients with cardiovascular disease. There are limited data on the effects of n-3 PUFA supplementation in patients with peripheral artery disease (PAD). MATERIALS AND METHODS:The OMEGA-PAD II trial was a double-blinded, randomized, placebo-controlled trial to assess the effect of 3 mo of high-dose oral n-3 PUFA supplementation on inflammation, endothelial function, and walking ability in patients with PAD. RESULTS:Twenty-four patients with claudication received 4.4 g/d of fish oil or placebo for 3 mo. Outcomes measured included high-sensitivity C-reactive protein levels, the omega-3 index, endothelial function as measured via flow-mediated vasodilation, walking impairment questionnaire, and a 6-min walk test. Plasma levels of specialized pro-resolving lipid mediators (SPMs) were measured by liquid-chromatography-tandem mass spectrometry. In patients treated with fish oil, the absolute mean omega-3 index significantly increased from baseline (fish oil: 7.2 ± 1.2%, P < 0.001; placebo: -0.4 ± 0.9%, P = 0.31; between-group P < 0.001). Furthermore, there were significant increases in several pathway markers of SPM biosynthesis, including several mono-hydroxyeicosapentaenoic acids and mono-hydroxydocosahexaenoic acids. We also observed significant increases in the SPM lipoxin A5 (fish oil: 0.57 ± 0.70 pg/mL, P = 0.05; placebo: 0.01 ± 0.38 pg/mL, P = 0.93; between-group P = 0.04) and resolvin E3 (fish oil: 154 ± 171 pg/mL, P = 0.04; placebo: 32 ± 54 pg/mL, P = 0.08; between-group P = 0.04). There were no significant changes in high-sensitivity C-reactive protein, flow-mediated vasodilation, walking impairment questionnaire, or 6-min walk test in the fish oil group. CONCLUSIONS:Fish oil increases SPMs in plasma of patients with PAD. Further studies are required to determine whether these early changes translate to clinical improvements in patients with PAD.

Project description:BackgroundTermination of acute inflammation is an active process orchestrated by lipid mediators (LM) derived from polyunsaturated fatty acids, referred to as specialized pro-resolving mediators (SPM). These mediators also provide novel therapeutic opportunities for treating inflammatory disease. However, the regulation of these molecules following acute myocardial infarction (MI) remains of interest.MethodsIn this prospective observational study we aimed to profile plasma levels of SPMs in ST-elevation MI (STEMI) patients during the first week following MI. Plasma LM concentrations were measured in patients with STEMI (n = 15) at three time points and compared with stable coronary artery disease (CAD; n = 10) and healthy controls (n = 10).FindingsOur main findings were: (i) Immediately after onset of MI and before peak troponin T levels, STEMI patients had markedly increased levels of SPMs as compared with healthy controls and stable CAD patients, with levels of these mediators declining during follow-up. (ii) The increase in SPMs primarily reflected an increase in docosapentaenoic acid- and docosahexaenoic acid-derived protectins. (iii) Several individual protectins were correlated with the rapid increase in neutrophil counts, but not with CRP. (iv) A shift in 5-LOX activity from the leukotriene B4 pathway to the pro-resolving RvTs was observed.InterpretationThe temporal regulation of SPMs indicates that resolution mechanisms are activated early during STEMI as part of an endogenous mechanism to initiate repair. Thus strategies to boost the activity and/or efficacy of these endogenous mechanisms may represent novel therapeutic opportunities for treatment of patients with MI. FUND: This work was supported by grants from the South-Eastern Norwegian regional health authority, the European Research Council under the European Union's Horizon 2020 research and innovation program, a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society, and the Barts Charity.

Dataset Information

Specialized pro-resolving lipid mediators in the inflammatory response: An update.

Publications

Specialized pro-resolving lipid mediators in the inflammatory response: An update.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets