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Int. J. Mol. Sci. 2018, 19(1), 114; https://doi.org/10.3390/ijms19010114

Sphingolipids in Ventilator Induced Lung Injury: Role of Sphingosine-1-Phosphate Lyase

1
Department of Bioengineering, University of Illinois at Chicago (UIC), Chicago, IL 60607, USA
2
Department of Pharmacology, University of Illinois at Chicago (UIC), Chicago, IL 60612, USA
3
Department of Pharmacology, Department of Medicine, National Jewish Health Center, Denver, CO 80206, USA
4
Department of Pediatrics, University of Illinois at Chicago (UIC), Chicago, IL 60612, USA
5
Department of Medicine, University of Illinois at Chicago (UIC), Chicago, IL 60612, USA
*
Author to whom correspondence should be addressed.
Received: 15 November 2017 / Revised: 21 December 2017 / Accepted: 27 December 2017 / Published: 1 January 2018
(This article belongs to the Special Issue Sphingolipids: Signals and Disease)
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Abstract

Mechanical ventilation (MV) performed in respiratory failure patients to maintain lung function leads to ventilator-induced lung injury (VILI). This study investigates the role of sphingolipids and sphingolipid metabolizing enzymes in VILI using a rodent model of VILI and alveolar epithelial cells subjected to cyclic stretch (CS). MV (0 PEEP (Positive End Expiratory Pressure), 30 mL/kg, 4 h) in mice enhanced sphingosine-1-phosphate lyase (S1PL) expression, and ceramide levels, and decreased S1P levels in lung tissue, thereby leading to lung inflammation, injury and apoptosis. Accumulation of S1P in cells is a balance between its synthesis catalyzed by sphingosine kinase (SphK) 1 and 2 and catabolism mediated by S1P phosphatases and S1PL. Thus, the role of S1PL and SphK1 in VILI was investigated using Sgpl1+/− and Sphk1−/− mice. Partial genetic deletion of Sgpl1 protected mice against VILI, whereas deletion of SphK1 accentuated VILI in mice. Alveolar epithelial MLE-12 cells subjected to pathophysiological 18% cyclic stretch (CS) exhibited increased S1PL protein expression and dysregulation of sphingoid bases levels as compared to physiological 5% CS. Pre-treatment of MLE-12 cells with S1PL inhibitor, 4-deoxypyridoxine, attenuated 18% CS-induced barrier dysfunction, minimized cell apoptosis and cytokine secretion. These results suggest that inhibition of S1PL that increases S1P levels may offer protection against VILI. View Full-Text
Keywords: sphingolipids; sphingosine-1-phosphate; S1P lyase; sphingosine kinases; lung injury; mechanical ventilation sphingolipids; sphingosine-1-phosphate; S1P lyase; sphingosine kinases; lung injury; mechanical ventilation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Suryadevara, V.; Fu, P.; Ebenezer, D.L.; Berdyshev, E.; Bronova, I.A.; Huang, L.S.; Harijith, A.; Natarajan, V. Sphingolipids in Ventilator Induced Lung Injury: Role of Sphingosine-1-Phosphate Lyase. Int. J. Mol. Sci. 2018, 19, 114.

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