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Mediators of Inflammation
Volume 2017, Article ID 5187368, 10 pages
Research Article

Nuclear Translocation of SGPP-1 and Decrease of SGPL-1 Activity Contribute to Sphingolipid Rheostat Regulation of Inflammatory Dendritic Cells

1Institute of General Pharmacology and Toxicology, pharmazentrum frankfurt/ZAFES, Hospital of the Goethe University, Frankfurt, Germany
2Institute of Clinical Pharmacology, pharmazentrum frankfurt, Hospital of the Goethe University, Frankfurt, Germany
3Institute of Nutritional Science, University of Potsdam, Potsdam, Germany

Correspondence should be addressed to Anja Schwiebs; ed.trufknarf-inu.dem@sbeiwhcs

Received 2 June 2017; Revised 22 August 2017; Accepted 3 October 2017; Published 11 December 2017

Academic Editor: Alice Alessenko

Copyright © 2017 Anja Schwiebs et al. 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.


A balanced sphingolipid rheostat is indispensable for dendritic cell function and survival and thus initiation of an immune response. Sphingolipid levels are dynamically maintained by the action of sphingolipid enzymes of which sphingosine kinases, S1P phosphatases (SGPP-1/2) and S1P lyase (SGPL-1), are pivotal in the balance of S1P and sphingosine levels. In this study, we present that SGPP-1 and SGPL-1 are regulated in inflammatory dendritic cells and contribute to S1P fate. TLR-dependent activation caused SGPL-1 protein downregulation with subsequent decrease of enzymatic activity by two-thirds. In parallel, confocal fluorescence microscopy revealed that endogenous SGPP-1 was expressed in nuclei of naive dendritic cells and was translocated into the cytoplasmatic compartment upon inflammatory stimulation resulting in dephosphorylation of S1P. Mass spectrometric determination showed that a part of the resulting sphingosine was released from the cell, increasing extracellular levels. Another route of diminishing intracellular S1P was possibly taken by its export via ATP-binding cassette transporter C1 which was upregulated in array analysis, while the S1P transporter, spinster homolog 2, was not relevant in dendritic cells. These investigations newly describe the sequential expression and localization of the endogenous S1P regulators SGPP-1 and SGPL-1 and highlight their contribution to the sphingolipid rheostat in inflammation.