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Impact of S1P Mimetics on Mesenteric Ischemia/Reperfusion Injury

Department of Medicine and Surgery, University of Parma, via Gramsci 14, 43126 Parma, Italy
Food and Drug Department, University of Parma, Parco Area delle Scienze 27/a, 43124 Parma, Italy
Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Author to whom correspondence should be addressed.
Pharmaceuticals 2020, 13(10), 298;
Received: 31 July 2020 / Revised: 24 September 2020 / Accepted: 7 October 2020 / Published: 9 October 2020
(This article belongs to the Section Pharmacology)
Mesenteric ischemia/reperfusion (I/R), following the transient deprivation of blood flow to the gut, triggers an acute flogistic process involving the disruption of endothelial and epithelial barriers integrity, the activation of immune cells, and the abundant release of inflammatory mediators. Among them, the lipid mediator sphingosine-1-phosphate (S1P) is involved in maintaining epithelial and endothelial barrier integrity and in governing the migration of immune cells through the interaction with S1P1–5 receptors. Therefore, the present work aims to investigate the involvement of S1P signaling in intestinal I/R-induced injury by studying the effects of FTY720, the non-selective S1P1,3–5 agonist, and comparing them with the responses to ozanimod, selective S1P1,5 agonist, in a murine model of gut I/R. Intestinal edema, gut and lung neutrophil infiltration, and oxidative stress were evaluated through biochemical and morphological assays. The collected results highlight the protective action of FTY720 against the inflammatory cascade elicited by mesenteric I/R injury, mainly through the control of vascular barrier integrity. While these beneficial effects were mimicked by ozanimod and can be therefore attributed largely to the effects exerted by FTY720 on S1P1, the recruitment of myeloid cells to the injured areas, limited by FTY720 but not by ozanimod, rather suggests the involvement of other receptor subtypes. View Full-Text
Keywords: sphingosine-1-phosphate; gut hypoxia-reperfusion; FTY720; ozanimod; inflammation; S1P1 sphingosine-1-phosphate; gut hypoxia-reperfusion; FTY720; ozanimod; inflammation; S1P1
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Potì, F.; Giorgio, C.; Zini, I.; Nofer, J.-R.; Vivo, V.; Palese, S.; Ballabeni, V.; Barocelli, E.; Bertoni, S. Impact of S1P Mimetics on Mesenteric Ischemia/Reperfusion Injury. Pharmaceuticals 2020, 13, 298.

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