PMID- 27148053
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160505
LR  - 20201001
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 7
DP  - 2016
TI  - Activation-Induced Cell Death of Dendritic Cells Is Dependent on Sphingosine 
      Kinase 1.
PG  - 94
LID - 10.3389/fphar.2016.00094 [doi]
LID - 94
AB  - Sphingosine 1-phosphate (S1P) is an immune modulatory lipid mediator and has been 
      implicated in numerous pathophysiological processes. S1P is produced by 
      sphingosine kinase 1 (Sphk1) and Sphk2. Dendritic cells (DCs) are central for the 
      direction of immune responses and crucially involved in autoimmunity and 
      cancerogenesis. In this study we examined the function and survival of bone 
      marrow-derived DCs under long-term inflammatory stimulation. We observed that 
      differentiated cells undergo activation-induced cell death (AICD) upon LPS 
      stimulation with an increased metabolic activity shortly after stimulation, 
      followed by a rapid activation of caspase 3 and subsequent augmented apoptosis. 
      Importantly, we highlight a profound role of Sphk1 in secretion of inflammatory 
      cytokines and survival of dendritic cells that might be mediated by a change in 
      sphingolipid levels as well as by a change in STAT3 expression. Cell growth 
      during differentiation of Sphk1-deficient cells treated with the functional S1P 
      receptor antagonist FTYP was reduced. Importantly, in dendritic cells we did not 
      observe a compensatory regulation of Sphk2 mRNA in Sphk1-deficient cells. 
      Instead, we discovered a massive increase in Sphk1 mRNA concentration upon 
      long-term stimulation with LPS in wild type cells that might function as an 
      attempt to rescue from inflammation-caused cell death. Taken together, in this 
      investigation we describe details of a crucial involvement of sphingolipids and 
      Sphk1 in AICD during long-term immunogenic activity of DCs that might play an 
      important role in autoimmunity and might explain the differences in immune 
      response observed in in vivo studies of Sphk1 modulation.
FAU - Schwiebs, Anja
AU  - Schwiebs A
AD  - Department of General Pharmacology and Toxicology, Pharmazentrum Frankfurt/ZAFES, 
      Clinic of the Goethe University Frankfurt, Germany.
FAU - Friesen, Olga
AU  - Friesen O
AD  - Department of General Pharmacology and Toxicology, Pharmazentrum Frankfurt/ZAFES, 
      Clinic of the Goethe University Frankfurt, Germany.
FAU - Katzy, Elisabeth
AU  - Katzy E
AD  - Department of General Pharmacology and Toxicology, Pharmazentrum Frankfurt/ZAFES, 
      Clinic of the Goethe University Frankfurt, Germany.
FAU - Ferreiros, Nerea
AU  - Ferreiros N
AD  - Department of Clinical Pharmacology, Pharmazentrum Frankfurt, Clinic of the 
      Goethe University Frankfurt, Germany.
FAU - Pfeilschifter, Josef M
AU  - Pfeilschifter JM
AD  - Department of General Pharmacology and Toxicology, Pharmazentrum Frankfurt/ZAFES, 
      Clinic of the Goethe University Frankfurt, Germany.
FAU - Radeke, Heinfried H
AU  - Radeke HH
AD  - Department of General Pharmacology and Toxicology, Pharmazentrum Frankfurt/ZAFES, 
      Clinic of the Goethe University Frankfurt, Germany.
LA  - eng
PT  - Journal Article
DEP - 20160415
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC4832589
OTO - NOTNLM
OT  - FTY720P
OT  - Fingolimod
OT  - S1P
OT  - activation-induced-cell-death
OT  - dendritic cells
OT  - sphingosine kinase 1
OT  - sphingosine kinase 2
OT  - sphingosine-1-phosphate
EDAT- 2016/05/06 06:00
MHDA- 2016/05/06 06:01
PMCR- 2016/04/15
CRDT- 2016/05/06 06:00
PHST- 2016/01/15 00:00 [received]
PHST- 2016/03/22 00:00 [accepted]
PHST- 2016/05/06 06:00 [entrez]
PHST- 2016/05/06 06:00 [pubmed]
PHST- 2016/05/06 06:01 [medline]
PHST- 2016/04/15 00:00 [pmc-release]
AID - 10.3389/fphar.2016.00094 [doi]
PST - epublish
SO  - Front Pharmacol. 2016 Apr 15;7:94. doi: 10.3389/fphar.2016.00094. eCollection 
      2016.