Sphingosine 1-Phosphate: A Novel Target for Lung Disorders

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2017 Mar 30

PMID 28352271

Citations 33

Authors

Sabira Mohammed

K B Harikumar

Affiliations

Soon will be listed here.

Abstract

Sphingosine 1-phosphate (S1P) is involved in a wide range of cellular processes, which include proliferation, apoptosis, lymphocyte egress, endothelial barrier function, angiogenesis, and inflammation. S1P is produced by two isoenzymes, namely, sphingosine kinase 1 and 2 (SphK1 and 2) and once produced, S1P can act both in an autocrine and paracrine manner. S1P can be dephosphorylated back to sphingosine by two phosphatases (SGPP 1 and 2) or can be irreversibly cleaved by S1P lyase. S1P has a diverse range of functions, which is mediated in a receptor dependent, through G-protein coupled receptors (S1PR1-5) or receptor independent manner, through intracellular targets such as HDACs and TRAF2. The involvement of S1P signaling has been confirmed in various disease conditions including lung diseases. The SphK inhibitors and S1PR modulators are currently under clinical trials for different pathophysiological conditions. There is a significant effort in targeting various components of S1P signaling for several diseases. This review focuses on the ways in which S1P signaling can be therapeutically targeted in lung disorders.

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References

Salinas N, Lopes C, Palma P, Oshima C, Bueno V . Lung tumor development in the presence of sphingosine 1-phosphate agonist FTY720. Pathol Oncol Res. 2009; 15(4):549-54. DOI: 10.1007/s12253-009-9152-2. View

Choi S, Camp S, Dan A, Garcia J, Dudek S, Leckband D . A genetic variant of cortactin linked to acute lung injury impairs lamellipodia dynamics and endothelial wound healing. Am J Physiol Lung Cell Mol Physiol. 2015; 309(9):L983-94. PMC: 4628987. DOI: 10.1152/ajplung.00062.2015. View

Sorrentino R, Bertolino A, Terlizzi M, Mattera Iacono V, Maiolino P, Cirino G . B cell depletion increases sphingosine-1-phosphate-dependent airway inflammation in mice. Am J Respir Cell Mol Biol. 2014; 52(5):571-83. DOI: 10.1165/rcmb.2014-0207OC. View

Brinkmann V, Billich A, Baumruker T, Heining P, Schmouder R, Francis G . Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Discov. 2010; 9(11):883-97. DOI: 10.1038/nrd3248. View

Bettoncelli G, Blasi F, Brusasco V, Centanni S, Corrado A, De Benedetto F . The clinical and integrated management of COPD. Sarcoidosis Vasc Diffuse Lung Dis. 2014; 31 Suppl 1:3-21. View

Hsu A, Zhang W, Lee J, An J, Ekambaram P, Liu J . Sphingosine-1-phosphate receptor-3 signaling up-regulates epidermal growth factor receptor and enhances epidermal growth factor receptor-mediated carcinogenic activities in cultured lung adenocarcinoma cells. Int J Oncol. 2012; 40(5):1619-26. PMC: 3797598. DOI: 10.3892/ijo.2012.1379. View

Sawicka E, Zuany-Amorim C, Manlius C, Trifilieff A, Brinkmann V, Kemeny D . Inhibition of Th1- and Th2-mediated airway inflammation by the sphingosine 1-phosphate receptor agonist FTY720. J Immunol. 2003; 171(11):6206-14. DOI: 10.4049/jimmunol.171.11.6206. View

Oyeniran C, Sturgill J, Hait N, Huang W, Avni D, Maceyka M . Aberrant ORM (yeast)-like protein isoform 3 (ORMDL3) expression dysregulates ceramide homeostasis in cells and ceramide exacerbates allergic asthma in mice. J Allergy Clin Immunol. 2015; 136(4):1035-46.e6. PMC: 4591101. DOI: 10.1016/j.jaci.2015.02.031. View

Trifilieff A, Fozard J . Sphingosine-1-phosphate-induced airway hyper-reactivity in rodents is mediated by the sphingosine-1-phosphate type 3 receptor. J Pharmacol Exp Ther. 2012; 342(2):399-406. DOI: 10.1124/jpet.112.191585. View

10.

Roviezzo F, Sorrentino R, Mattera Iacono V, Brancaleone V, Terlizzi M, Riemma M . Disodium cromoglycate inhibits asthma-like features induced by sphingosine-1-phosphate. Pharmacol Res. 2016; 113(Pt A):626-635. DOI: 10.1016/j.phrs.2016.09.014. View

11.

Okuwa H, Kanno T, Fujita Y, Gotoh A, Tabata C, Fukuoka K . Sphingosine suppresses mesothelioma cell proliferation by inhibiting PKC-δ and inducing cell cycle arrest at the G(0)/G(1) phase. Cell Physiol Biochem. 2012; 30(4):995-1004. DOI: 10.1159/000341476. View

12.

Chiba Y, Takeuchi H, Sakai H, Misawa M . SKI-II, an inhibitor of sphingosine kinase, ameliorates antigen-induced bronchial smooth muscle hyperresponsiveness, but not airway inflammation, in mice. J Pharmacol Sci. 2010; 114(3):304-10. DOI: 10.1254/jphs.10202fp. View

13.

Chiba Y, Suzuki K, Uechi M, Kurihara E, Goto K, Sakai H . Downregulation of sphingosine-1-phosphate receptors in bronchial smooth muscle of mouse experimental asthma. Pharmacol Res. 2010; 62(4):357-63. DOI: 10.1016/j.phrs.2010.05.005. View

14.

Pyne S, Adams D, Pyne N . Sphingosine 1-phosphate and sphingosine kinases in health and disease: Recent advances. Prog Lipid Res. 2016; 62:93-106. DOI: 10.1016/j.plipres.2016.03.001. View

15.

Huang L, Berdyshev E, Tran J, Xie L, Chen J, Ebenezer D . Sphingosine-1-phosphate lyase is an endogenous suppressor of pulmonary fibrosis: role of S1P signalling and autophagy. Thorax. 2015; 70(12):1138-48. DOI: 10.1136/thoraxjnl-2014-206684. View

16.

Cui H, Okamoto Y, Yoshioka K, Du W, Takuwa N, Zhang W . Sphingosine-1-phosphate receptor 2 protects against anaphylactic shock through suppression of endothelial nitric oxide synthase in mice. J Allergy Clin Immunol. 2013; 132(5):1205-1214.e9. DOI: 10.1016/j.jaci.2013.07.026. View

17.

Proia R, Hla T . Emerging biology of sphingosine-1-phosphate: its role in pathogenesis and therapy. J Clin Invest. 2015; 125(4):1379-87. PMC: 4409021. DOI: 10.1172/JCI76369. View

18.

Matheu M, Teijaro J, Walsh K, Greenberg M, Marsolais D, Parker I . Three phases of CD8 T cell response in the lung following H1N1 influenza infection and sphingosine 1 phosphate agonist therapy. PLoS One. 2013; 8(3):e58033. PMC: 3606384. DOI: 10.1371/journal.pone.0058033. View

19.

Spiegel S, Milstien S . The outs and the ins of sphingosine-1-phosphate in immunity. Nat Rev Immunol. 2011; 11(6):403-15. PMC: 3368251. DOI: 10.1038/nri2974. View

20.

Shi H, Cheng D, Yi L, Huo X, Zhang K, Zhen G . Association between ORMDL3 polymorphism and susceptibility to asthma: a meta-analysis. Int J Clin Exp Med. 2015; 8(3):3173-83. PMC: 4443040. View