Table of Contents
Journal of Allergy
Volume 2012 (2012), Article ID 154174, 14 pages
http://dx.doi.org/10.1155/2012/154174
Review Article

Sphingolipids: A Potential Molecular Approach to Treat Allergic Inflammation

Wai Y. Sun1,2,3 and Claudine S. Bonder1,2,3,4

1Centre for Cancer Biology, SA Pathology, Frome Road, Adelaide, SA 5000, Australia
2School of Medicine, University of Adelaide, Adelaide, SA 5000, Australia
3Cooperative Research Centre for Biomarker Translation, La Trobe University, Bundoora, VIC 3086, Australia
4School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, SA 5000, Australia

Received 10 August 2012; Revised 15 October 2012; Accepted 30 October 2012

Academic Editor: Robert J. Bischof

Copyright © 2012 Wai Y. Sun and Claudine S. Bonder. 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.

Linked References

  1. P. Jiang, J. Liu, X. B. Yan, and R. Y. Liu, “Several interleukin-4 and interleukin-13 gene single nucleotide polymorphisms among Chinese asthmatic patients.,” Allergy and Asthma Proceedings, vol. 30, no. 4, pp. 413–418, 2009. View at Google Scholar · View at Scopus
  2. A. B. Kay, “Allergy and allergic diseases. First of two parts,” New England Journal of Medicine, vol. 344, no. 1, pp. 30–37, 2001. View at Publisher · View at Google Scholar
  3. K. Hakim-Rad, M. Metz, and M. Maurer, “Mast cells: makers and breakers of allergic inflammation,” Current Opinion in Allergy and Clinical Immunology, vol. 9, no. 5, pp. 427–430, 2009. View at Publisher · View at Google Scholar · View at Scopus
  4. M. A. Grimbaldeston, M. Metz, M. Yu, M. Tsai, and S. J. Galli, “Effector and potential immunoregulatory roles of mast cells in IgE-associated acquired immune responses,” Current Opinion in Immunology, vol. 18, no. 6, pp. 751–760, 2006. View at Publisher · View at Google Scholar · View at Scopus
  5. N. Iriyoshi, K. Takeuchi, A. Yuta, K. Ukai, and Y. Sakakura, “Increased expression of histamine H1 receptor mRNA in allergic rhinitis,” Clinical and Experimental Allergy, vol. 26, no. 4, pp. 379–385, 1996. View at Publisher · View at Google Scholar · View at Scopus
  6. B. L. Jones and G. L. Kearns, “Histamine: new thoughts about a familiar mediator,” Clinical Pharmacology and Therapeutics, vol. 89, no. 2, pp. 189–197, 2011. View at Publisher · View at Google Scholar · View at Scopus
  7. A. McIlroy, G. Caron, S. Blanchard et al., “Histamine and prostaglandin E2 up-regulate the production of Th2-attracting chemokines (CCL17 and CCL22) and down-regulate IFN-γ-induced CXCL10 production by immature human dendritic cells,” Immunology, vol. 117, no. 4, pp. 507–516, 2006. View at Publisher · View at Google Scholar · View at Scopus
  8. M. Jutel, T. Watanabe, M. Akdis, K. Blaser, and C. A. Akdis, “Immune regulation by histamine opinion,” Current Opinion in Immunology, vol. 14, no. 6, pp. 735–740, 2002. View at Publisher · View at Google Scholar · View at Scopus
  9. T. C. T. M. van der Pouw Kraan, A. Snijders, L. C. M. Boeije et al., “Histamine inhibits the production of interleukin-12 through interaction with H2 receptors,” Journal of Clinical Investigation, vol. 102, no. 10, pp. 1866–1873, 1998. View at Google Scholar · View at Scopus
  10. M. Dy and E. Schneider, “Histamine-cytokine connection in immunity and hematopoiesis,” Cytokine and Growth Factor Reviews, vol. 15, no. 5, pp. 393–410, 2004. View at Publisher · View at Google Scholar · View at Scopus
  11. A. Huwiler, F. Döll, S. Ren et al., “Histamine increases sphingosine kinase-1 expression and activity in the human arterial endothelial cell line EA.hy 926 by a PKC-α-dependent mechanism,” Biochimica et Biophysica Acta, vol. 1761, no. 3, pp. 367–376, 2006. View at Publisher · View at Google Scholar · View at Scopus
  12. M. Jutel, M. Akdis, and C. A. Akdis, “Histamine, histamine receptors and their role in immune pathology,” Clinical and Experimental Allergy, vol. 39, no. 12, pp. 1786–1800, 2009. View at Publisher · View at Google Scholar · View at Scopus
  13. D. MacGlashan Jr, “Histamine: a mediator of inflammation,” Journal of Allergy and Clinical Immunology, vol. 112, supplement 4, pp. S53–S59, 2003. View at Publisher · View at Google Scholar · View at Scopus
  14. R. Torres, C. Decastellarnau, L. L. Ferrer, A. Puigdemont, L. F. Santamaría, and F. De Mora, “Mast cells induce upregulation of P-selectin and intercellular adhesion molecule 1 on carotid endothelial cells in a new in vitro model of mast cell to endothelial cell communication,” Immunology and Cell Biology, vol. 80, no. 2, pp. 170–177, 2002. View at Publisher · View at Google Scholar · View at Scopus
  15. T. Maruko, T. Nakahara, K. Sakamoto et al., “Involvement of the βγ subunits of G proteins in the cAMP response induced by stimulation of the histamine H1 receptor,” Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 372, no. 2, pp. 153–159, 2005. View at Publisher · View at Google Scholar · View at Scopus
  16. R. A. Bakker, S. B. J. Schoonus, M. J. Smit, H. Timmerman, and R. Leurs, “Histamine H1-receptor activation of nuclear factor-κB: roles for Gβγ- and Gαq/11-subunits in constitutive and agonist-mediated signaling,” Molecular Pharmacology, vol. 60, no. 5, pp. 1133–1142, 2001. View at Google Scholar · View at Scopus
  17. M. J. Smit, M. Hoffmann, H. Timmerman, and R. Leurs, “Molecular properties and signalling pathways of the histamine H1 receptor,” Clinical and Experimental Allergy, Supplement, vol. 29, supplement 3, pp. 19–28, 1999. View at Google Scholar · View at Scopus
  18. R. Leurs, M. K. Church, and M. Taglialatela, “H1-antihistamines: inverse agonism, anti-inflammatory actions and cardiac effects,” Clinical and Experimental Allergy, vol. 32, no. 4, pp. 489–498, 2002. View at Publisher · View at Google Scholar · View at Scopus
  19. C. Shayo, N. Fernandez, B. L. Legnazzi et al., “Histamine H2 receptor desensitization: involvement of a select array of G protein-coupled receptor kinases,” Molecular Pharmacology, vol. 60, no. 5, pp. 1049–1056, 2001. View at Google Scholar · View at Scopus
  20. M. S. Repka-Ramirez, “New concepts of histamine receptors and actions,” Current Allergy and Asthma Reports, vol. 3, no. 3, pp. 227–231, 2003. View at Google Scholar · View at Scopus
  21. L. M. Lichtenstein and E. Gillespie, “The effects of the H1 and H2 antihistamines on “allergic” histamine release and its inhibition by histamine,” Journal of Pharmacology and Experimental Therapeutics, vol. 192, no. 2, pp. 441–450, 1975. View at Google Scholar · View at Scopus
  22. M. R. Emerson, D. M. Orentas, S. G. Lynch, and S. M. LeVine, “Activation of histamine H2 receptors ameliorates experimental allergic encephalomyelitis,” NeuroReport, vol. 13, no. 11, pp. 1407–1410, 2002. View at Google Scholar · View at Scopus
  23. J. D. Del Valle and I. Gantz, “Novel insights into histamine H2 receptor biology,” American Journal of Physiology, vol. 273, no. 5, pp. G987–G996, 1997. View at Google Scholar · View at Scopus
  24. M. B. Emanuel, “Histamine and the antiallergic antihistamines: a history of their discoveries,” Clinical and Experimental Allergy, Supplement, vol. 29, supplement 3, pp. 1–11, 1999. View at Google Scholar · View at Scopus
  25. P. J. Bryce, C. B. Mathias, K. L. Harrison, T. Watanabe, R. S. Geha, and H. C. Oettgen, “The H1 histamine receptor regulates allergic lung responses,” Journal of Clinical Investigation, vol. 116, no. 6, pp. 1624–1632, 2006. View at Publisher · View at Google Scholar · View at Scopus
  26. A. R. Qasem, C. Bucolo, M. Baiula et al., “Contribution of α4β1 integrin to the antiallergic effect of levocabastine,” Biochemical Pharmacology, vol. 76, no. 6, pp. 751–762, 2008. View at Publisher · View at Google Scholar · View at Scopus
  27. Y. J. Jang, J. H. Wang, J. S. Kim, H. J. Kwon, N. K. Yeo, and B. J. Lee, “Levocetirizine inhibits rhinovirus-induced ICAM-1 and cytokine expression and viral replication in airway epithelial cells,” Antiviral Research, vol. 81, no. 3, pp. 226–233, 2009. View at Publisher · View at Google Scholar · View at Scopus
  28. D. Axelrod and L. Bielory, “Fexofenadine hydrochloride in the treatment of allergic disease: a review,” Journal of Asthma and Allergy, no. 1, pp. 19–29, 2008. View at Google Scholar · View at Scopus
  29. E. W. Gelfand, Z. H. Cui, K. Takeda, A. Kanehiro, and A. Joetham, “Fexofenadine modulates T-cell function, preventing allergen-induced airway inflammation and hyperresponsiveness,” Journal of Allergy and Clinical Immunology, vol. 110, no. 1, pp. 85–95, 2002. View at Publisher · View at Google Scholar · View at Scopus
  30. J. O. Warner, “A double-blinded, randomized, placebo-controlled trial of cetirizine in preventing the onset of asthma in children with atopic dermatitis: 18 months' treatment and 18 months' posttreatment follow-up,” Journal of Allergy and Clinical Immunology, vol. 108, no. 6, pp. 929–937, 2001. View at Publisher · View at Google Scholar · View at Scopus
  31. G. Ciprandi, M. A. Tosca, C. Cosentino, A. M. Riccio, G. Passalacqua, and G. W. Canonica, “Effects of fexofenadine and other antihistamines on components of the allergic response: adhesion molecules,” Journal of Allergy and Clinical Immunology, vol. 112, supplement 4, pp. S78–S82, 2003. View at Publisher · View at Google Scholar · View at Scopus
  32. S. L. Spector, C. F. Nicodemus, J. Corren et al., “Comparison of the bronchodilatory effects of cetirizine, albuterol, and both together versus placebo in patients with mild-to-moderate asthma,” Journal of Allergy and Clinical Immunology, vol. 96, no. 2, pp. 174–181, 1995. View at Publisher · View at Google Scholar · View at Scopus
  33. F. Siebenhaar, F. Degener, T. Zuberbier, P. Martus, and M. Maurer, “High-dose desloratadine decreases wheal volume and improves cold provocation thresholds compared with standard-dose treatment in patients with acquired cold urticaria: a randomized, placebo-controlled, crossover study,” Journal of Allergy and Clinical Immunology, vol. 123, no. 3, pp. 672–679, 2009. View at Publisher · View at Google Scholar · View at Scopus
  34. T. Zuberbier, “Pharmacological rationale for the treatment of chronic urticaria with second-generation non-sedating antihistamines at higher-than-standard doses,” Journal of the European Academy of Dermatology and Venereology, vol. 26, no. 1, pp. 9–18, 2012. View at Publisher · View at Google Scholar · View at Scopus
  35. R. C. Johnson, T. N. Mayadas, P. S. Frenette et al., “Blood cell dynamics in P-selectin-deficient mice,” Blood, vol. 86, no. 3, pp. 1106–1114, 1995. View at Google Scholar · View at Scopus
  36. K. Egami, T. Murohara, M. Aoki, and T. Matsuishi, “Ischemia-induced angiogenesis: role of inflammatory response mediated by P-selectin,” Journal of Leukocyte Biology, vol. 79, no. 5, pp. 971–976, 2006. View at Publisher · View at Google Scholar · View at Scopus
  37. A. Etzioni, “Defects in the leukocyte adhesion cascade,” Clinical Reviews in Allergy and Immunology, vol. 38, no. 1, pp. 54–60, 2010. View at Publisher · View at Google Scholar · View at Scopus
  38. T. M. Zollner, K. Asadullah, and M. P. Schön, “Targeting leukocyte trafficking to inflamed skin-still an attractive therapeutic approach?” Experimental Dermatology, vol. 16, no. 1, pp. 1–12, 2007. View at Publisher · View at Google Scholar · View at Scopus
  39. B. Rossi and G. Constantin, “Anti-selectin therapy for the treatment of inflammatory diseases,” Inflammation and Allergy-Drug Targets, vol. 7, no. 2, pp. 85–93, 2008. View at Publisher · View at Google Scholar · View at Scopus
  40. D. J. Lefer, D. M. Flynn, M. L. Phillips, M. Ratcliffe, and A. J. Buda, “A novel sialyl Lewis(x) analog attenuates neutrophil accumulation and myocardial necrosis after ischemia and reperfusion,” Circulation, vol. 90, no. 5, pp. 2390–2401, 1994. View at Google Scholar · View at Scopus
  41. E. A. Gill, Y. Kong, and L. D. Horwitz, “An oligosaccharide sialyl-Lewis(x) analogue does not reduce myocardial infarct size after ischemia and reperfusion in dogs,” Circulation, vol. 94, no. 3, pp. 542–546, 1996. View at Google Scholar · View at Scopus
  42. Y. Birnbaum, M. Patterson, and R. A. Kloner, “The effect of CY1503, a sialyl lewis(x) analog blocker of the selectin adhesion molecules, on infarct size and “no-reflow” in the rabbit model of acute myocardial infarction/reperfusion,” Journal of Molecular and Cellular Cardiology, vol. 29, no. 8, pp. 2013–2025, 1997. View at Publisher · View at Google Scholar · View at Scopus
  43. A. Kutlar, K. I. Ataga, L. McMahon et al., “A potent oral P-selectin blocking agent improves microcirculatory blood flow and a marker of endothelial cell injury in patients with sickle cell disease,” American Journal of Hematology, vol. 87, no. 5, pp. 536–539, 2012. View at Publisher · View at Google Scholar
  44. R. Anaya-Prado, J. R. Ramos-Kelly, L. H. Toledo-Pereyra, J. Walsh, and P. A. Ward, “Multiple selectin blockade with a small-molecule selectin inhibitor does not affect survival after a second inflammatory challenge with nonlethal LPS,” Journal of Investigative Surgery, vol. 15, no. 3, pp. 171–180, 2002. View at Publisher · View at Google Scholar · View at Scopus
  45. M. S. Co, N. F. Landolfi, J. O. Nagy et al., “Properties and pharmacokinetics of two humanized antibodies specific for L-selectin,” Immunotechnology, vol. 4, no. 3-4, pp. 253–266, 1999. View at Publisher · View at Google Scholar · View at Scopus
  46. K. Wang, X. Zhou, Z. Zhou et al., “Recombinant soluble P-selectin glycoprotein ligand-Ig (rPSGL-Ig) attenuates infarct size and myeloperoxidase activity in a canine model of ischemia-reperfusion,” Thrombosis and Haemostasis, vol. 88, no. 1, pp. 149–154, 2002. View at Google Scholar · View at Scopus
  47. K. Ley, “The role of selectins in inflammation and disease,” Trends in Molecular Medicine, vol. 9, no. 6, pp. 263–268, 2003. View at Publisher · View at Google Scholar · View at Scopus
  48. P. Kubes and S. M. Kerfoot, “Leukocyte recruitment in the microcirculation: the rolling paradigm revisited,” News in Physiological Sciences, vol. 16, no. 2, pp. 76–80, 2001. View at Google Scholar · View at Scopus
  49. M. D. Catalina, P. Estess, and M. H. Siegelman, “Selective requirements for leukocyte adhesion molecules in models of acute and chronic cutaneous inflammation: participation of E- and P- but not L-selectin,” Blood, vol. 93, no. 2, pp. 580–589, 1999. View at Google Scholar · View at Scopus
  50. S. M. Pitson, J. A. Powell, and C. S. Bonder, “Regulation of sphingosine kinase in hematological malignancies and other cancers,” Anti-Cancer Agents in Medicinal Chemistry, vol. 11, no. 9, pp. 799–809, 2011. View at Google Scholar
  51. A. J. Melendez, “Sphingosine kinase signalling in immune cells: potential as novel therapeutic targets,” Biochimica et Biophysica Acta, vol. 1784, no. 1, pp. 66–75, 2008. View at Publisher · View at Google Scholar · View at Scopus
  52. W. Q. Lai, W. S. F. Wong, and B. P. Leung, “Sphingosine kinase and sphingosine 1-phosphate in asthma,” Bioscience Reports, vol. 31, no. 2, pp. 145–150, 2011. View at Publisher · View at Google Scholar · View at Scopus
  53. M. Podbielska, H. Krotkiewski, and E. L. Hogan, “Signaling and regulatory functions of bioactive sphingolipids as therapeutic targets in multiple sclerosis,” Neurochemical Research, vol. 37, no. 6, pp. 1154–1169, 2012. View at Publisher · View at Google Scholar
  54. P. F. Hu, Y. Chen, P. F. Cai, L. F. Jiang, and L. D. Wu, “Sphingosine-1-phosphate: a potential therapeutic target for rheumatoid arthritis,” Molecular Biology Reports, vol. 38, no. 6, pp. 4225–4230, 2011. View at Publisher · View at Google Scholar
  55. C. F. Jessup, C. S. Bonder, S. M. Pitson, and P. T. Coates, “The sphingolipid rheostat: a potential target for improving pancreatic islet survival and function,” Endocrine, Metabolic & Immune Disorders-Drug Targets, vol. 11, no. 4, pp. 262–272, 2011. View at Google Scholar
  56. S. M. Pitson, R. J. D'Andrea, L. Vandeleur et al., “Human sphingosine kinase: purification, molecular cloning and characterization of the native and recombinant enzymes,” Biochemical Journal, vol. 350, no. 2, pp. 429–441, 2000. View at Publisher · View at Google Scholar · View at Scopus
  57. H. Liu, M. Sugiura, V. E. Nava et al., “Molecular cloning and functional characterization of a novel mammalian sphingosine kinase type 2 isoform,” Journal of Biological Chemistry, vol. 275, no. 26, pp. 19513–19520, 2000. View at Publisher · View at Google Scholar · View at Scopus
  58. M. L. Allende, T. Sasaki, H. Kawai et al., “Mice deficient in sphingosine kinase 1 are rendered lymphopenic by FTY720,” Journal of Biological Chemistry, vol. 279, no. 50, pp. 52487–52492, 2004. View at Publisher · View at Google Scholar · View at Scopus
  59. B. Zemann, B. Kinzel, M. Müller et al., “Sphingosine kinase type 2 is essential for lymphopenia induced by the immunomodulatory drug FTY720,” Blood, vol. 107, no. 4, pp. 1454–1458, 2006. View at Publisher · View at Google Scholar · View at Scopus
  60. R. Pappu, S. R. Schwab, I. Cornelissen et al., “Promotion of lymphocyte egress into blood and lymph by distinct sources of sphingosine-1-phosphate,” Science, vol. 316, no. 5822, pp. 295–298, 2007. View at Publisher · View at Google Scholar · View at Scopus
  61. A. Olivera, T. Kohama, L. Edsall et al., “Sphingosine kinase expression increases intracellular sphingosine-1- phosphate and promotes cell growth and survival,” Journal of Cell Biology, vol. 147, no. 3, pp. 545–557, 1999. View at Publisher · View at Google Scholar · View at Scopus
  62. J. R. Gamble, W. Y. Sun, X. Li et al., “Sphingosine kinase-1 associates with integrin αVβ 3 to mediate endothelial cell survival,” American Journal of Pathology, vol. 175, no. 5, pp. 2217–2225, 2009. View at Publisher · View at Google Scholar · View at Scopus
  63. S. M. Pitson, “Regulation of sphingosine kinase and sphingolipid signaling,” Trends in Biochemical Sciences, vol. 36, no. 2, pp. 97–107, 2011. View at Publisher · View at Google Scholar · View at Scopus
  64. M. Maceyka, H. Sankala, N. C. Hait et al., “SphK1 and SphK2, sphingosine kinase isoenzymes with opposing functions in sphingolipid metabolism,” Journal of Biological Chemistry, vol. 280, no. 44, pp. 37118–37129, 2005. View at Publisher · View at Google Scholar · View at Scopus
  65. K. G. Lim, F. Tonelli, E. Berdyshev et al., “Inhibition kinetics and regulation of sphingosine kinase 1 expression in prostate cancer cells: functional differences between sphingosine kinase 1a and 1b,” International Journal of Biochemistry & Cell Biology, vol. 44, no. 9, pp. 1457–1464, 2012. View at Google Scholar
  66. W. Y. Sun, L. D. Abeynaike, S. Escarbe et al., “Rapid histamine-induced neutrophil recruitment is sphingosine kinase-1 dependent,” American Journal of Pathology, vol. 180, no. 4, pp. 1740–1750, 2012. View at Publisher · View at Google Scholar
  67. P. Xia, J. R. Gamble, K. A. Rye et al., “Tumor necrosis factor-α induces adhesion molecule expression through the sphingosine kinase pathway,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 24, pp. 14196–14201, 1998. View at Publisher · View at Google Scholar · View at Scopus
  68. A. J. Melendez and F. B. M. Ibrahim, “Antisense knockdown of sphingosine kinase 1 in human macrophages inhibits C5a receptor-dependent signal transduction, Ca2+ signals, enzyme release, cytokine production, and chemotaxis,” Journal of Immunology, vol. 173, no. 3, pp. 1596–1603, 2004. View at Google Scholar · View at Scopus
  69. S. M. Pitson, P. A. B. Moretti, J. R. Zebol et al., “Activation of sphingosine kinase 1 by ERK1/2-mediated phosphorylation,” EMBO Journal, vol. 22, no. 20, pp. 5491–5500, 2003. View at Publisher · View at Google Scholar · View at Scopus
  70. R. V. Stahelin, J. H. Hwang, J. H. Kim et al., “The mechanism of membrane targeting of human sphingosine kinase 1,” Journal of Biological Chemistry, vol. 280, no. 52, pp. 43030–43038, 2005. View at Publisher · View at Google Scholar · View at Scopus
  71. K. E. Jarman, P. A. B. Moretti, J. R. Zebol, and S. M. Pitson, “Translocation of sphingosine kinase 1 to the plasma membrane is mediated by calcium- and integrin-binding protein 1,” Journal of Biological Chemistry, vol. 285, no. 1, pp. 483–492, 2010. View at Publisher · View at Google Scholar · View at Scopus
  72. R. K. Barr, H. E. Lynn, P. A. B. Moretti, Y. Khew-Goodall, and S. M. Pitson, “Deactivation of sphingosine kinase 1 by protein phosphatase 2A,” Journal of Biological Chemistry, vol. 283, no. 50, pp. 34994–35002, 2008. View at Publisher · View at Google Scholar · View at Scopus
  73. M. R. Pitman, R. K. Barr, B. L. Gliddon, A. M. Magarey, P. A. B. Moretti, and S. M. Pitson, “A critical role for the protein phosphatase 2A B′α regulatory subunit in dephosphorylation of sphingosine kinase 1,” International Journal of Biochemistry and Cell Biology, vol. 43, no. 3, pp. 342–347, 2011. View at Publisher · View at Google Scholar · View at Scopus
  74. N. C. Hait, A. Bellamy, S. Milstien, T. Kordula, and S. Spiegel, “Sphingosine kinase type 2 activation by ERK-mediated phosphorylation,” Journal of Biological Chemistry, vol. 282, no. 16, pp. 12058–12065, 2007. View at Publisher · View at Google Scholar · View at Scopus
  75. K. J. French, R. S. Schrecengost, B. D. Lee et al., “Discovery and evaluation of inhibitors of human sphingosine kinase,” Cancer Research, vol. 63, no. 18, pp. 5962–5969, 2003. View at Google Scholar · View at Scopus
  76. L. C. Edsall, J. R. Van Brocklyn, O. Cuvillier, B. Kleuser, and S. Spiegel, “N,N-dimethylsphingosine is a potent competitive inhibitor of sphingosine kinase but not of protein kinase C: modulation of cellular levels of sphingosine 1-phosphate and ceramide,” Biochemistry, vol. 37, no. 37, pp. 12892–12898, 1998. View at Publisher · View at Google Scholar · View at Scopus
  77. Y. Kharel, S. Lee, A. H. Snyder et al., “Sphingosine kinase 2 is required for modulation of lymphocyte traffic by FTY720,” Journal of Biological Chemistry, vol. 280, no. 44, pp. 36865–36872, 2005. View at Publisher · View at Google Scholar · View at Scopus
  78. P. Gao, Y. K. Peterson, R. A. Smith, and C. D. Smith, “Characterization of isoenzyme-selective inhibitors of human sphingosine kinases,” PLoS One, vol. 7, no. 9, Article ID e44543, 2012. View at Google Scholar
  79. M. E. Schnute, M. D. McReynolds, T. Kasten et al., “Modulation of cellular S1P levels with a novel, potent and specific inhibitor of sphingosine kinase-1,” Biochemical Journal, vol. 444, no. 1, pp. 79–88, 2012. View at Publisher · View at Google Scholar
  80. M. M. Price, C. A. Oskeritzian, Y. T. Falanga et al., “A specific sphingosine kinase 1 inhibitor attenuates airway hyperresponsiveness and inflammation in a mast cell-dependent murine model of allergic asthma,” Journal of Allergy and Clinical Immunology. In press.
  81. Y. Kharel, T. P. Mathews, A. M. Gellett et al., “Sphingosine kinase type 1 inhibition reveals rapid turnover of circulating sphingosine 1-phosphate,” Biochemical Journal, vol. 440, no. 3, pp. 345–353, 2011. View at Publisher · View at Google Scholar
  82. K. J. French, Y. Zhuang, L. W. Maines et al., “Pharmacology and antitumor activity of ABC294640, a selective inhibitor of sphingosine kinase-2,” Journal of Pharmacology and Experimental Therapeutics, vol. 333, no. 1, pp. 129–139, 2010. View at Publisher · View at Google Scholar · View at Scopus
  83. Y. Kharel, M. Raje, M. Gao et al., “Sphingosine kinase type 2 inhibition elevates circulating sphingosine 1-phosphate,” Biochemical Journal, vol. 447, no. 1, pp. 149–157, 2012. View at Publisher · View at Google Scholar
  84. M. G. Sanna, S. K. Wang, P. J. Gonzalez-Cabrera et al., “Enhancement of capillary leakage and restoration of lymphocyte egress by a chiral S1P1 antagonist in vivo,” Nature Chemical Biology, vol. 2, no. 8, pp. 434–441, 2006. View at Publisher · View at Google Scholar · View at Scopus
  85. F. W. Foss Jr, A. H. Snyder, M. D. Davis et al., “Synthesis and biological evaluation of γ-aminophosphonates as potent, subtype-selective sphingosine 1-phosphate receptor agonists and antagonists,” Bioorganic and Medicinal Chemistry, vol. 15, no. 2, pp. 663–677, 2007. View at Publisher · View at Google Scholar · View at Scopus
  86. M. D. Davis, J. J. Clemens, T. L. Macdonald, and K. R. Lynch, “Sphingosine 1-phosphate analogs as receptor antagonists,” Journal of Biological Chemistry, vol. 280, no. 11, pp. 9833–9841, 2005. View at Publisher · View at Google Scholar · View at Scopus
  87. M. Osada, Y. Yatomi, T. Ohmori, H. Ikeda, and Y. Ozaki, “Enhancement of sphingosine 1-phosphate-induced migration of vascular endothelial cells and smooth muscle cells by an EDG-5 antagonist,” Biochemical and Biophysical Research Communications, vol. 299, no. 3, pp. 483–487, 2002. View at Publisher · View at Google Scholar · View at Scopus
  88. R. Tao, H. E. Hoover, J. Zhang, N. Honbo, C. C. Alano, and J. S. Karliner, “Cardiomyocyte S1P1 receptor-mediated extracellular signal-related kinase signaling and desensitization,” Journal of Cardiovascular Pharmacology, vol. 53, no. 6, pp. 486–494, 2009. View at Publisher · View at Google Scholar · View at Scopus
  89. A. J. Snider, K. Alexa Orr Gandy, and L. M. Obeid, “Sphingosine kinase: role in regulation of bioactive sphingolipid mediators in inflammation,” Biochimie, vol. 92, no. 6, pp. 707–715, 2010. View at Publisher · View at Google Scholar · View at Scopus
  90. Z. Tanfin, M. Serrano-Sanchez, and D. Leiber, “ATP-binding cassette ABCC1 is involved in the release of sphingosine 1-phosphate from rat uterine leiomyoma ELT3 cells and late pregnant rat myometrium,” Cellular Signalling, 2011. View at Publisher · View at Google Scholar · View at Scopus
  91. Y. Yatomi, Y. Ozaki, T. Ohmori, and Y. Igarashi, “Sphingosine 1-phosphate: synthesis and release,” Prostaglandins and Other Lipid Mediators, vol. 64, no. 1–4, pp. 107–122, 2001. View at Publisher · View at Google Scholar · View at Scopus
  92. P. Mitra, C. A. Oskeritzian, S. G. Payne, M. A. Beaven, S. Milstien, and S. Spiegel, “Role of ABCC1 in export of sphingosine-1-phosphate from mast cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 44, pp. 16394–16399, 2006. View at Publisher · View at Google Scholar · View at Scopus
  93. N. Murata, K. Sato, J. Kon et al., “Interaction of sphingosine 1-phosphate with plasma components, including lipoproteins, regulates the lipid receptor-mediated actions,” Biochemical Journal, vol. 352, no. 3, pp. 809–815, 2000. View at Publisher · View at Google Scholar · View at Scopus
  94. S. Aoki, M. Osada, M. Kaneko, Y. Ozaki, and Y. Yatomi, “Fluid shear stress enhances the sphingosine 1-phosphate responses in cell-cell interactions between platelets and endothelial cells,” Biochemical and Biophysical Research Communications, vol. 358, no. 4, pp. 1054–1057, 2007. View at Publisher · View at Google Scholar · View at Scopus
  95. A. Olivera and S. Spiegel, “Sphingosine-1-phosphate as second messenger in cell proliferation induced by PDGF and FCS mitogens,” Nature, vol. 365, no. 6446, pp. 557–560, 1993. View at Publisher · View at Google Scholar · View at Scopus
  96. Y. Yatomi, Y. Igarashi, L. Yang et al., “Sphingosine 1-phosphate, a bioactive sphingolipid abundantly stored in platelets, is a normal constituent of human plasma and serum,” Journal of Biochemistry, vol. 121, no. 5, pp. 969–973, 1997. View at Google Scholar · View at Scopus
  97. S. R. Schwab, J. P. Pereira, M. Matloubian, Y. Xu, Y. Huang, and J. G. Cyster, “Immunology: lymphocyte sequestration through S1P lyase inhibition and disruption of S1P gradients,” Science, vol. 309, no. 5741, pp. 1735–1739, 2005. View at Publisher · View at Google Scholar · View at Scopus
  98. K. Venkataraman, S. Thangada, J. Michaud et al., “Extracellular export of sphingosine kinase-1a contributes to the vascular S1P gradient,” Biochemical Journal, vol. 397, no. 3, pp. 461–471, 2006. View at Publisher · View at Google Scholar · View at Scopus
  99. S. M. Hammad, T. A. Taha, A. Nareika, K. R. Johnson, M. F. Lopes-Virella, and L. M. Obeid, “Oxidized LDL immune complexes induce release of sphingosine kinase in human U937 monocytic cells,” Prostaglandins and Other Lipid Mediators, vol. 79, no. 1-2, pp. 126–140, 2006. View at Publisher · View at Google Scholar · View at Scopus
  100. N. C. Hait, J. Allegood, M. Maceyka et al., “Regulation of histone acetylation in the nucleus by sphingosine-1-phosphate,” Science, vol. 325, no. 5945, pp. 1254–1257, 2009. View at Publisher · View at Google Scholar · View at Scopus
  101. S. E. Alvarez, K. B. Harikumar, N. C. Hait et al., “Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2,” Nature, vol. 465, no. 7301, pp. 1084–1088, 2010. View at Publisher · View at Google Scholar · View at Scopus
  102. G. M. Strub, M. Paillard, J. Liang et al., “Sphingosine-1-phosphate produced by sphingosine kinase 2 in mitochondria interacts with prohibitin 2 to regulate complex IV assembly and respiration,” FASEB Journal, vol. 25, no. 2, pp. 600–612, 2011. View at Publisher · View at Google Scholar · View at Scopus
  103. V. Limaye, X. Li, C. Hahn et al., “Sphingosine kinase-1 enhances endothelial cell survival through a PECAM-1-dependent activation of PI-3K/Akt and regulation of Bcl-2 family members,” Blood, vol. 105, no. 8, pp. 3169–3177, 2005. View at Publisher · View at Google Scholar · View at Scopus
  104. B. Oskouian, P. Soonyakumaran, A. D. Borowsky et al., “Sphingosine-1-phosphate lyase potentiates apoptosis via p53- and p38-dependent pathways and is down-regulated in colon cancer,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 46, pp. 17384–17389, 2006. View at Publisher · View at Google Scholar · View at Scopus
  105. S. Colié, P. P. Van Veldhoven, B. Kedjouar et al., “Disruption of sphingosine 1-phosphate lyase confers resistance to chemotherapy and promotes oncogenesis through Bcl-2/Bcl-xL upregulation,” Cancer Research, vol. 69, no. 24, pp. 9346–9353, 2009. View at Publisher · View at Google Scholar · View at Scopus
  106. Y. Liu, R. Wada, T. Yamashita et al., “Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation,” Journal of Clinical Investigation, vol. 106, no. 8, pp. 951–961, 2000. View at Google Scholar · View at Scopus
  107. S. M. Pitson, “Regulation of sphingosine kinase and sphingolipid signaling,” Trends in Biochemical Sciences, vol. 36, no. 2, pp. 97–107, 2011. View at Publisher · View at Google Scholar · View at Scopus
  108. M. Matloubian, C. G. Lo, G. Cinamon et al., “Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1,” Nature, vol. 427, no. 6972, pp. 355–360, 2004. View at Publisher · View at Google Scholar · View at Scopus
  109. A. Olivera, C. Eisner, Y. Kitamura et al., “Sphingosine kinase 1 and sphingosine-1-phosphate receptor 2 are vital to recovery from anaphylactic shock in mice,” Journal of Clinical Investigation, vol. 120, no. 5, pp. 1429–1440, 2010. View at Publisher · View at Google Scholar · View at Scopus
  110. P. S. Jolly, M. Bektas, A. Olivera et al., “Transactivation of sphingosine-1-phosphate receptors by fcεRI triggering is required for normal mast cell degranulation and chemotaxis,” Journal of Experimental Medicine, vol. 199, no. 7, pp. 959–970, 2004. View at Publisher · View at Google Scholar · View at Scopus
  111. M. Kono, Y. Mi, Y. Liu et al., “The sphingosine-1-phosphate receptors S1P1, S1P2, and S1P3 function coordinately during embryonic angiogenesis,” Journal of Biological Chemistry, vol. 279, no. 28, pp. 29367–29373, 2004. View at Publisher · View at Google Scholar · View at Scopus
  112. Y. Y. Lan, A. De Creus, B. L. Colvin et al., “The sphingosine-1-phosphate receptor agonist FTY720 modulates dendritic cell trafficking in vivo,” American Journal of Transplantation, vol. 5, no. 11, pp. 2649–2659, 2005. View at Publisher · View at Google Scholar · View at Scopus
  113. W. Wang, M. H. Graeler, and E. J. Goetzl, “Type 4 sphingosine 1-phosphate G protein-coupled receptor (S1P4) transduces S1P effects on T cell proliferation and cytokine secretion without signaling migration,” FASEB Journal, vol. 19, no. 12, pp. 1731–1733, 2005. View at Publisher · View at Google Scholar · View at Scopus
  114. K. Mizugishi, T. Yamashita, A. Olivera, G. F. Miller, S. Spiegel, and R. L. Proia, “Essential role for sphingosine kinases in neural and vascular development,” Molecular and Cellular Biology, vol. 25, no. 24, pp. 11113–11121, 2005. View at Publisher · View at Google Scholar · View at Scopus
  115. K. Mizugishi, C. Li, A. Olivera et al., “Maternal disturbance in activated sphingolipid metabolism causes pregnancy loss in mice,” Journal of Clinical Investigation, vol. 117, no. 10, pp. 2993–3006, 2007. View at Publisher · View at Google Scholar · View at Scopus
  116. S. C. Diesner, A. Olivera, S. Dillahunt et al., “Sphingosine-kinase 1 and 2 contribute to oral sensitization and effector phase in a mouse model of food allergy,” Immunology Letters, vol. 141, no. 2, pp. 210–219, 2012. View at Publisher · View at Google Scholar
  117. D. A. Baker, J. Barth, R. Chang, L. M. Obeid, and G. S. Gilkeson, “Genetic sphingosine kinase 1 deficiency significantly decreases synovial inflammation and joint erosions in murine TNF-α-induced arthritis,” Journal of Immunology, vol. 185, no. 4, pp. 2570–2579, 2010. View at Publisher · View at Google Scholar · View at Scopus
  118. D. A. Baker, J. Eudaly, C. D. Smith, L. M. Obeid, and G. S. Gilkeson, “Impact of sphingosine kinase 2 deficiency on the development of TNF-alpha-induced inflammatory arthritis,” Rheumatology International. In press.
  119. A. J. Ammit, A. T. Hastie, L. C. Edsall et al., “Sphingosine 1-phosphate modulates human airway smooth muscle cell functions that promote inflammation and airway remodeling in asthma.,” The FASEB Journal, vol. 15, no. 7, pp. 1212–1214, 2001. View at Google Scholar · View at Scopus
  120. F. Cordts, S. Pitson, C. Tabeling et al., “Expression profile of the sphingosine kinase signalling system in the lung of patients with chronic obstructive pulmonary disease,” Life Sciences, vol. 89, no. 21-22, pp. 806–811, 2011. View at Publisher · View at Google Scholar
  121. P. Puneet, C. T. Yap, L. Wong et al., “SphK1 regulates proinflammatory responses associated with endotoxin and polymicrobial sepsis,” Science, vol. 328, no. 5983, pp. 1290–1294, 2010. View at Publisher · View at Google Scholar · View at Scopus
  122. Q. Li, C. Wang, Q. Zhang, C. Tang, N. Li, and J. Li, “The role of sphingosine kinase 1 in patients with severe acute pancreatitis,” Annals of Surgery, vol. 255, no. 5, pp. 954–962, 2012. View at Publisher · View at Google Scholar
  123. W. Q. Lai, A. W. Irwan, H. H. Goh et al., “Anti-inflammatory effects of sphingosine kinase modulation in inflammatory arthritis.,” Journal of Immunology, vol. 181, no. 11, pp. 8010–8017, 2008. View at Google Scholar · View at Scopus
  124. M. R. Pitman and S. M. Pitson, “Inhibitors of the sphingosine kinase pathway as potential therapeutics,” Current Cancer Drug Targets, vol. 10, no. 4, pp. 354–367, 2010. View at Publisher · View at Google Scholar · View at Scopus
  125. D. Marsolais and H. Rosen, “Chemical modulators of sphingosine-1-phosphate receptors as barrier-oriented therapeutic molecules,” Nature Reviews Drug Discovery, vol. 8, no. 4, pp. 297–307, 2009. View at Publisher · View at Google Scholar · View at Scopus
  126. S. V. Madhunapantula, J. Hengst, R. Gowda, T. E. Fox, J. K. Yun, and G. P. Robertson, “Targeting sphingosine kinase-1 to inhibit melanoma,” Pigment Cell & Melanoma Research, vol. 25, no. 2, pp. 259–274, 2012. View at Google Scholar
  127. T. Nishiuma, Y. Nishimura, T. Okada et al., “Inhalation of sphingosine kinase inhibitor attenuates airway inflammation in asthmatic mouse model,” American Journal of Physiology, vol. 294, no. 6, pp. L1085–L1093, 2008. View at Publisher · View at Google Scholar · View at Scopus
  128. L. Kappos, E. W. Radue, P. O'Connor et al., “A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis,” New England Journal of Medicine, vol. 362, no. 5, pp. 387–401, 2010. View at Publisher · View at Google Scholar · View at Scopus
  129. S. W. Paugh, S. G. Payne, S. E. Barbour, S. Milstien, and S. Spiegel, “The immunosuppressant FTY720 is phosphorylated by sphingosine kinase type 2,” FEBS Letters, vol. 554, no. 1-2, pp. 189–193, 2003. View at Publisher · View at Google Scholar · View at Scopus
  130. D. A. Vessey, M. Kelley, J. Zhang, L. Li, R. Tao, and J. S. Karliner, “Dimethylsphingosine and FTY720 inhibit the SK1 form but activate the SK2 form of sphingosine kinase from rat heart,” Journal of Biochemical and Molecular Toxicology, vol. 21, no. 5, pp. 273–279, 2007. View at Publisher · View at Google Scholar · View at Scopus
  131. F. Tonelli, K. G. Lim, C. Loveridge et al., “FTY720 and (S)-FTY720 vinylphosphonate inhibit sphingosine kinase 1 and promote its proteasomal degradation in human pulmonary artery smooth muscle, breast cancer and androgen-independent prostate cancer cells,” Cellular Signalling, vol. 22, no. 10, pp. 1536–1542, 2010. View at Publisher · View at Google Scholar · View at Scopus
  132. K. G. Lim, F. Tonelli, Z. Li et al., “FTY720 analogues as sphingosine kinase 1 inhibitors: enzyme inhibition kinetics, allosterism, proteasomal degradation and actin rearrangement in MCF-7 breast cancer cells,” Journal of Biological Chemistry, vol. 286, no. 21, pp. 18633–18640, 2011. View at Publisher · View at Google Scholar · View at Scopus
  133. D. Pchejetski, T. Bohler, L. Brizuela et al., “FTY720 (fingolimod) sensitizes prostate cancer cells to radiotherapy by inhibition of sphingosine kinase-1,” Cancer Research, vol. 70, no. 21, pp. 8651–8661, 2010. View at Publisher · View at Google Scholar · View at Scopus
  134. H. Tedesco-Silva, M. I. Lorber, C. E. Foster et al., “FTY720 and everolimus in de novo renal transplant patients at risk for delayed graft function: results of an exploratory one-yr multicenter study,” Clinical Transplantation, vol. 23, no. 5, pp. 589–599, 2009. View at Publisher · View at Google Scholar · View at Scopus
  135. A. J. Hoitsma, E. S. Woodle, D. Abramowicz, P. Proot, and Y. Vanrenterghem, “FTY720 combined with tacrolimus in de novo renal transplantation: 1-year, multicenter, open-label randomized study,” Nephrology Dialysis Transplantation, vol. 26, no. 11, pp. 3802–3805, 2011. View at Publisher · View at Google Scholar
  136. M. R. Pitman, J. M. Woodcock, A. F. Lopez, and S. M. Pitson, “Molecular targets of FTY720 (fingolimod),” Current Molecular Medicine. In press.
  137. V. Beljanski, C. S. Lewis, and C. D. Smith, “Antitumor activity of sphingosine kinase 2 inhibitor ABC294640 and sorafenib in hepatocellular carcinoma xenografts,” Cancer Biology and Therapy, vol. 11, no. 5, pp. 524–534, 2011. View at Publisher · View at Google Scholar · View at Scopus
  138. L. W. Maines, L. R. Fitzpatrick, C. L. Green, Y. Zhuang, and C. D. Smith, “Efficacy of a novel sphingosine kinase inhibitor in experimental Crohn's disease,” Inflammopharmacology, vol. 18, no. 2, pp. 73–85, 2010. View at Publisher · View at Google Scholar · View at Scopus
  139. Y. Shi, H. Rehman, V. K. Ramshesh et al., “Sphingosine kinase-2 inhibition improves mitochondrial function and survival after hepatic ischemia-reperfusion,” Journal of Hepatology, vol. 56, no. 1, pp. 137–145, 2012. View at Google Scholar
  140. L. R. Fitzpatrick, C. Green, L. W. Maines, and C. D. Smith, “Experimental osteoarthritis in rats is attenuated by ABC294640, a selective inhibitor of sphingosine kinase-2,” Pharmacology, vol. 87, no. 3-4, pp. 135–143, 2011. View at Publisher · View at Google Scholar · View at Scopus
  141. J. W. Antoon, M. D. White, W. D. Meacham et al., “Antiestrogenic effects of the novel sphingosine kinase-2 inhibitor ABC294640,” Endocrinology, vol. 151, no. 11, pp. 5124–5135, 2010. View at Publisher · View at Google Scholar · View at Scopus
  142. J. Michaud, M. Kohno, R. L. Proia, and T. Hla, “Normal acute and chronic inflammatory responses in sphingosine kinase 1 knockout mice,” FEBS Letters, vol. 580, no. 19, pp. 4607–4612, 2006. View at Publisher · View at Google Scholar · View at Scopus
  143. W. Q. Lai, A. W. Irwan, H. H. Goh, A. J. Melendez, I. B. McInnes, and B. P. Leung, “Distinct roles of sphingosine kinase 1 and 2 in murine collagen-induced arthritis,” Journal of Immunology, vol. 183, no. 3, pp. 2097–2103, 2009. View at Publisher · View at Google Scholar · View at Scopus
  144. M. Kono, I. A. Belyantseva, A. Skoura et al., “Deafness and stria vascularis defects in S1P2 receptor-null mice,” Journal of Biological Chemistry, vol. 282, no. 14, pp. 10690–10696, 2007. View at Publisher · View at Google Scholar · View at Scopus
  145. A. J. MacLennan, P. R. Carney, W. J. Zhu et al., “An essential role for the H218/AGR16/Edg-5/LPB2 sphingosine 1-phosphate receptor in neuronal excitability,” European Journal of Neuroscience, vol. 14, no. 2, pp. 203–209, 2001. View at Publisher · View at Google Scholar · View at Scopus
  146. J. A. Cohen and J. Chun, “Mechanisms of fingolimod's efficacy and adverse effects in multiple sclerosis,” Annals of Neurology, vol. 69, no. 5, pp. 759–777, 2011. View at Publisher · View at Google Scholar · View at Scopus
  147. K. Bachmaier, E. Guzman, T. Kawamura, X. Gao, and A. B. Malik, “Sphingosine kinase 1 mediation of expression of the anaphylatoxin receptor C5L2 dampens the inflammatory response to endotoxin,” PLoS One, vol. 7, no. 2, Article ID e30742, 2012. View at Google Scholar
  148. W. Y. Sun, S. M. Pitson, and C. S. Bonder, “Tumor necrosis factor-induced neutrophil adhesion occurs via sphingosine kinase-1-dependent activation of endothelial α5β 1 integrin,” American Journal of Pathology, vol. 177, no. 1, pp. 436–446, 2010. View at Publisher · View at Google Scholar · View at Scopus
  149. H. Kase, Y. Hattori, T. Jojima et al., “Globular adiponectin induces adhesion molecule expression through the sphingosine kinase pathway in vascular endothelial cells,” Life Sciences, vol. 81, no. 11, pp. 939–943, 2007. View at Publisher · View at Google Scholar · View at Scopus
  150. K. Shimamura, Y. Takashiro, N. Akiyama, T. Hirabayashi, and T. Murayama, “Expression of adhesion molecules by sphingosine 1-phosphate and histamine in endothelial cells,” European Journal of Pharmacology, vol. 486, no. 2, pp. 141–150, 2004. View at Publisher · View at Google Scholar · View at Scopus
  151. K. Matsushita, C. N. Morrell, and C. J. Lowenstein, “Sphingosine 1-phosphate activates Weibel-Palade body exocytosis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 31, pp. 11483–11487, 2004. View at Publisher · View at Google Scholar · View at Scopus
  152. H. Rosen, P. J. Gonzalez-Cabrera, M. G. Sanna, and S. Brown, “Sphingosine 1-phosphate receptor signaling,” Annual Review of Biochemistry, vol. 78, pp. 743–768, 2009. View at Publisher · View at Google Scholar · View at Scopus
  153. T. Hla and V. Brinkmann, “Sphingosine 1-phosphate (S1P): physiology and the effects of S1P receptor modulation,” Neurology, vol. 76, supplement 3, no. 8, pp. S3–S8, 2011. View at Publisher · View at Google Scholar · View at Scopus
  154. Y. Liu, J. Jiang, H. Xiao et al., “Topical application of FTY720 and cyclosporin A prolong corneal graft survival in mice,” Molecular Vision, vol. 18, pp. 624–633, 2012. View at Google Scholar
  155. R. Nagahama, T. Matoba, K. Nakano, S. Kim-Mitsuyama, K. Sunagawa, and K. Egashira, “Nanoparticle-mediated delivery of pioglitazone enhances therapeutic neovascularization in a murine model of hindlimb ischemia,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 32, no. 10, pp. 2427–2434, 2012. View at Publisher · View at Google Scholar