Effect of ether glycerol lipids on interleukin-1β release and experimental autoimmune encephalomyelitis

Stephanie D. Boomkamp, Hoe-Sup Byun, Satvir Ubhi, Hui-Rong Jiang, Susan Pyne, Robert Bittman, Nigel J. Pyne

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Abstract

We have assessed the effect of two ether glycerol lipids, 77-6 ((2S, 3R)-4-(Tetradecyloxy)-2-amino-1,3-butanediol) and 56-5 ((S)-2-Amino-3-O-hexadecyl-1-propanol), which are substrates for sphingosine kinases, on inflammatory responses. Treatment of differentiated U937 macrophage-like cells with 77-6 but not 56-5 enhanced IL-1β release; either alone or in the presence of LPS. The stimulatory effect of sphingosine or 77-6 on LPS-stimulated IL-1β release was reduced by pretreatment of cells with the caspase-1 inhibitor, Ac-YVAD-CHO, thereby indicating a role for the inflammasome. The enhancement of LPS-stimulated IL-1β release in response to sphingosine, but not 77-6, was reduced by pretreatment of cells with the cathepsin B inhibitor, CA074Me, indicating a role for lysosomal destabilization in the effect of sphingosine. Administration of 56-5 to mice increased disease progression in an experimental autoimmune encephalomyelitis model and this was associated with a considerable increase in the infiltration of CD4+ T-cells, CD11b+ monocytes and F4/80+ macrophages in the spinal cord. 56-5 and 77-6 were without effect on the degradation of myc-tagged sphingosine 1-phosphate 1 receptor in CCL39 cells. Therefore, the effect of 56-5 on EAE disease progression is likely to be independent of the inflammasome or the sphingosine 1-phosphate 1 receptor. However, 56-5 is chemically similar to platelet activating factor and the exacerbation of EAE disease progression might be linked to platelet activating factor receptor signaling.
Original languageEnglish
Pages (from-to)2-11
Number of pages10
JournalChemistry and Physics of Lipids
Volume194
Early online date14 Jul 2015
DOIs
Publication statusPublished - 1 Jan 2016

Keywords

  • Caspase-1
  • sphingosine
  • multiple sclerosis
  • interleukin-1
  • inflammasome
  • ether glycerol lipids

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