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Nils Helge Schebb, Hartmut Kühn, Astrid Stefanie Kahnt, Katharina M. Rund, Valerie B. O’Donnell, Nicolas Flamand, Marc L. Peters-Golden, Per‐Johan Jakobsson, Karsten Henrich Weylandt, Nadine Rohwer and 8 more
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.
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Schebb, N. H., Kühn, H., Kahnt, A. S., Rund, K. M., O’Donnell, V. B., Flamand, N., Peters-Golden, M. L., Jakobsson, P., Weylandt, K. H., Rohwer, N., Murphy, R. C., Geißlinger, G., FitzGerald, G. A., Hanson, J., Dahlgren, C., Alnouri, M. W., Offermanns, S., & Steinhilber, D. (2022). Formation, Signaling and Occurrence of Specialized Pro-Resolving Lipid Mediators—What is the Evidence so far? Frontiers in Pharmacology, 13, 838782. https://doi.org/10.3389/fphar.2022.838782
Schebb, Nils Helge, et al. "Formation, Signaling and Occurrence of Specialized Pro-Resolving Lipid Mediators—What is the Evidence so far?" Frontiers in Pharmacology, vol. 13, 2022, pp. 838782, https://doi.org/10.3389/fphar.2022.838782.
Schebb, Nils Helge, Hartmut Kühn, Astrid Stefanie Kahnt, Katharina M. Rund, Valerie B. O’Donnell, Nicolas Flamand, Marc L. Peters-Golden, et al. "Formation, Signaling and Occurrence of Specialized Pro-Resolving Lipid Mediators—What is the Evidence so far?" Frontiers in Pharmacology 13 (2022): 838782. https://doi.org/10.3389/fphar.2022.838782.
Schebb N. H., Kühn H., Kahnt A. S. [и др.] Formation, Signaling and Occurrence of Specialized Pro-Resolving Lipid Mediators—What is the Evidence so far? // Frontiers in Pharmacology. — 2022. — Vol. 13. — P. 838782. — URL: https://doi.org/10.3389/fphar.2022.838782
@article{schebb2022formation,
title = {{Formation, Signaling and Occurrence of Specialized Pro-Resolving Lipid Mediators—What is the Evidence so far?}},
author = {Nils Helge Schebb and Hartmut Kühn and Astrid Stefanie Kahnt and Katharina M. Rund and Valerie B. O’Donnell and Nicolas Flamand and Marc L. Peters-Golden and Per‐Johan Jakobsson and Karsten Henrich Weylandt and Nadine Rohwer and Robert C. Murphy and Gerd Geißlinger and Garret A. FitzGerald and Julien Hanson and Cláes Dahlgren and Mohamad Wessam Alnouri and Stefan Offermanns and Dieter Steinhilber},
journal = {Frontiers in Pharmacology},
year = {2022},
volume = {13},
pages = {838782},
doi = {10.3389/fphar.2022.838782},
url = {https://doi.org/10.3389/fphar.2022.838782}
}TY - JOUR AU - Schebb, Nils Helge AU - Kühn, Hartmut AU - Kahnt, Astrid Stefanie AU - Rund, Katharina M. AU - O’Donnell, Valerie B. AU - Flamand, Nicolas AU - Peters-Golden, Marc L. AU - Jakobsson, Per‐Johan AU - Weylandt, Karsten Henrich AU - Rohwer, Nadine AU - Murphy, Robert C. AU - Geißlinger, Gerd AU - FitzGerald, Garret A. AU - Hanson, Julien AU - Dahlgren, Cláes AU - Alnouri, Mohamad Wessam AU - Offermanns, Stefan AU - Steinhilber, Dieter TI - Formation, Signaling and Occurrence of Specialized Pro-Resolving Lipid Mediators—What is the Evidence so far? JO - Frontiers in Pharmacology VL - 13 SP - 838782 PY - 2022 DA - 2022/03/02 DO - 10.3389/fphar.2022.838782 UR - https://doi.org/10.3389/fphar.2022.838782 ER -
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