@article{ImeriFalleggerZivkovicetal.2014,
  author    = {Imeri, Faik and Fallegger, Daniel and Zivkovic, Aleksandra and Schwalm, Stephanie and Enzmann, Gaby and Blankenbach, Kira and Heringdorf, Dagmar Meyer Zu and Homann, Thomas and Kleuser, Burkhard and Pfeilschifter, Josef and Engelhardt, Britta and Stark, Holger and Huwiler, Andrea},
  title     = {Novel oxazolo-oxazole derivatives of FTY720 reduce endothelial cell permeability, immune cell chemotaxis and symptoms of experimental autoimmune encephalomyelitis in mice},
  series = {Neuropharmacology},
  volume    = {85},
  journal   = {Neuropharmacology},
  publisher = {Elsevier},
  address   = {Oxford},
  issn      = {0028-3908},
  doi       = {10.1016/j.neuropharm.2014.05.012},
  pages     = {314 -- 327},
  year      = {2014},
  abstract  = {The immunomodulatory FTY720 (fingolimod) is presently approved for the treatment of relapsing-remitting multiple sclerosis. It is a prodrug that acts by modulating sphingosine 1-phosphate (S1P) receptor signaling. In this study, we have developed and characterized two novel oxazolo-oxazole derivatives of FTY720, ST-968 and the oxy analog ST-1071, which require no preceding activating phosphorylation, and proved to be active in intact cells and triggered S1P(1) and S1P(3), but not S1P(2), receptor internalization as a result of receptor activation. Functionally, ST-968 and ST-1071 acted similar to FTY720 to abrogate S1P-triggered chemotaxis of mouse splenocytes, mouse T cells and human U937 cells, and reduced TNFa- and LPS-stimulated endothelial cell permeability. The compounds also reduced TNF alpha-induced ICAM-1 and VCAM-1 mRNA expression, but restored TNF alpha-mediated downregulation of PECAM-1 mRNA expression. In an in vivo setting, the application of ST-968 or ST-1071 to mice resulted in a reduction of blood lymphocytes and significantly reduced the clinical symptoms of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice comparable to FTY720 either by prophylactic or therapeutic treatment. In parallel to the reduced clinical symptoms, infiltration of immune cells in the brain was strongly reduced, and in isolated tissues of brain and spinal cord, the mRNA and protein expressions of ICAM-1 and VCAM-1, as well as of matrix metalloproteinase-9 were reduced by all compounds, whereas PECAM-1 and tissue inhibitor of metalloproteinase TIMP-1 were upregulated. In summary, the data suggest that these novel butterfly derivatives of FTY720 could have considerable implication for future therapies of multiple sclerosis and other autoimmune diseases. (C) 2014 Elsevier Ltd. All rights reserved.},
  language  = {en}
}
@misc{ArltSchwiebsJaptoketal.2014,
  author    = {Arlt, Olga and Schwiebs, Anja and Japtok, Lukasz and Rueger, Katja and Katzy, Elisabeth and Kleuser, Burkhard and Radeke, Heinfried H.},
  title     = {Sphingosine-1-Phosphate modulates dendritic cell function: focus on non-migratory effects in vitro and in vivo},
  series = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology},
  volume    = {34},
  journal   = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology},
  number    = {1},
  publisher = {Karger},
  address   = {Basel},
  issn      = {1015-8987},
  doi       = {10.1159/000362982},
  pages     = {27 -- 44},
  year      = {2014},
  abstract  = {Dendritic cells (DCs) are the cutting edge in innate and adaptive immunity. The major functions of these antigen presenting cells are the capture, endosomal processing and presentation of antigens, providing them an exclusive ability to provoke adaptive immune responses and to induce and control tolerance. Immature DCs capture and process antigens, migrate towards secondary lymphoid organs where they present antigens to naive T cells in a well synchronized sequence of procedures referred to as maturation. Indeed, recent research indicated that sphingolipids are modulators of essential steps in DC homeostasis. It has been recognized that sphingolipids not only modulate the development of DC subtypes from precursor cells but also influence functional activities of DCs such as antigen capture, and cytokine profiling. Thus, it is not astonishing that sphingolipids and sphingolipid metabolism play a substantial role in inflammatory diseases that are modulated by DCs. Here we highlight the function of sphingosine 1-phosphate (S1P) on DC homeostasis and the role of SIP and SW metabolism in inflammatory diseases.},
  language  = {en}
}