Effect of ether glycerol lipids on interleukin-1β release and experimental autoimmune encephalomyelitis
Boomkamp, Stephanie D. and Byun, Hoe-Sup and Ubhi, Satvir and Jiang, Hui-Rong and Pyne, Susan and Bittman, Robert and Pyne, Nigel J. (2016) Effect of ether glycerol lipids on interleukin-1β release and experimental autoimmune encephalomyelitis. Chemistry and Physics of Lipids, 194. pp. 2-11. ISSN 0009-3084
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Text (Boomkamp-etal-CPL-2015-Effect-of-ether-glycerol-lipids-on-interleukin)
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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.
Creators(s): |
Boomkamp, Stephanie D., Byun, Hoe-Sup, Ubhi, Satvir, Jiang, Hui-Rong, Pyne, Susan ![]() ![]() | Item type: | Article |
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ID code: | 54188 |
Keywords: | Caspase-1, sphingosine, multiple sclerosis, interleukin-1, inflammasome, ether glycerol lipids, Pharmacy and materia medica, Pharmacology, Toxicology and Pharmaceutics(all) |
Subjects: | Medicine > Pharmacy and materia medica |
Department: | Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences |
Depositing user: | Pure Administrator |
Date deposited: | 08 Sep 2015 07:53 |
Last modified: | 20 Jan 2021 23:25 |
Related URLs: | |
URI: | https://strathprints.strath.ac.uk/id/eprint/54188 |
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