Formation, Signaling and Occurrence of Specialized Pro-Resolving Lipid Mediators-What is the Evidence so far?

Autor:	Schebb NH; Chair of Food Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, Wuppertal, Germany., Kühn H; Department of Biochemistry, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany., Kahnt AS; Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Frankfurt, Germany., Rund KM; Chair of Food Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, Wuppertal, Germany., O'Donnell VB; School of Medicine, Systems Immunity Research Institute, School of Medicine, Cardiff University, Cardiff, United Kingdom., Flamand N; Département de Médecine, Faculté de Médecine, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Canada Excellence Research Chair on the Microbiome-Endocannabinoidome Axis in Metabolic Health (CERC-MEND), Université Laval, Québec, QC, Canada., Peters-Golden M; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, United States., Jakobsson PJ; Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Weylandt KH; Division of Medicine, Department of Gastroenterology, Metabolism and Oncology, Ruppin General Hospital, Brandenburg Medical School, Neuruppin, Germany., Rohwer N; Division of Medicine, Department of Gastroenterology, Metabolism and Oncology, Ruppin General Hospital, Brandenburg Medical School, Neuruppin, Germany.; Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany., Murphy RC; Department of Pharmacology, University of Colorado-Denver, Aurora, CO, United States., Geisslinger G; Institute of Clinical Pharmacology, Pharmazentrum Frankfurt, University Hospital of Goethe-University, Frankfurt, Germany.; Fraunhofer Institute for Translational Medicine and Pharmacology, ITMP and Fraunhofer Cluster of Excellence for Immune Mediated Diseases, CIMD, Frankfurt, Germany., FitzGerald GA; Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Hanson J; Laboratory of Molecular Pharmacology, GIGA-Molecular Biology of Diseases, University of Liège, Liège, Belgium.; Laboratory of Medicinal Chemistry, Centre for Interdisciplinary Research on Medicines (CIRM), University of Liège, Liège, Belgium., Dahlgren C; Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Alnouri MW; Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany., Offermanns S; Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.; Center for Molecular Medicine, Goethe University Frankfurt, Frankfurt, Germany., Steinhilber D; Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Frankfurt, Germany.; Fraunhofer Institute for Translational Medicine and Pharmacology, ITMP and Fraunhofer Cluster of Excellence for Immune Mediated Diseases, CIMD, Frankfurt, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in pharmacology [Front Pharmacol] 2022 Mar 02; Vol. 13, pp. 838782. Date of Electronic Publication: 2022 Mar 02 (Print Publication: 2022).
DOI:	10.3389/fphar.2022.838782
Abstrakt:	Formation of specialized pro-resolving lipid mediators (SPMs) such as lipoxins or resolvins usually involves arachidonic acid 5-lipoxygenase (5-LO, ALOX5) and different types of arachidonic acid 12- and 15-lipoxygenating paralogues (15-LO1, ALOX15; 15-LO2, ALOX15B; 12-LO, ALOX12). Typically, SPMs are thought to be formed via consecutive steps of oxidation of polyenoic fatty acids such as arachidonic acid, eicosapentaenoic acid or docosahexaenoic acid. One hallmark of SPM formation is that reported levels of these lipid mediators are much lower than typical pro-inflammatory mediators including the monohydroxylated fatty acid derivatives (e.g., 5-HETE), leukotrienes or certain cyclooxygenase-derived prostaglandins. Thus, reliable detection and quantification of these metabolites is challenging. This paper is aimed at critically evaluating i) the proposed biosynthetic pathways of SPM formation, ii) the current knowledge on SPM receptors and their signaling cascades and iii) the analytical methods used to quantify these pro-resolving mediators in the context of their instability and their low concentrations. Based on current literature it can be concluded that i) there is at most, a low biosynthetic capacity for SPMs in human leukocytes. ii) The identity and the signaling of the proposed G-protein-coupled SPM receptors have not been supported by studies in knock-out mice and remain to be validated. iii) In humans, SPM levels were neither related to dietary supplementation with their ω-3 polyunsaturated fatty acid precursors nor were they formed during the resolution phase of an evoked inflammatory response. iv) The reported low SPM levels cannot be reliably quantified by means of the most commonly reported methodology. Overall, these questions regarding formation, signaling and occurrence of SPMs challenge their role as endogenous mediators of the resolution of inflammation. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Schebb, Kühn, Kahnt, Rund, O’Donnell, Flamand, Peters-Golden, Jakobsson, Weylandt, Rohwer, Murphy, Geisslinger, FitzGerald, Hanson, Dahlgren, Alnouri, Offermanns and Steinhilber.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu