title: Effect of ether glycerol lipids on interleukin-1β release and experimental autoimmune encephalomyelitis.
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.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Science, University of Strathclyde, Glasgow G4 0RE, UK.
authors.forename: Stephanie D
authors.initials: SD
authors.lastname: Boomkamp
authors.affiliation: Department of Chemistry and Biochemistry, Queens College, The City University of New York, Flushing, NY 11367-1597, USA.
authors.forename: Hoe-Sup
authors.initials: HS
authors.lastname: Byun
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Science, University of Strathclyde, Glasgow G4 0RE, UK.
authors.forename: Satvir
authors.initials: S
authors.lastname: Ubhi
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Science, University of Strathclyde, Glasgow G4 0RE, UK.
authors.forename: Hui-Rong
authors.initials: HR
authors.lastname: Jiang
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Science, University of Strathclyde, Glasgow G4 0RE, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Pyne
authors.affiliation: Department of Chemistry and Biochemistry, Queens College, The City University of New York, Flushing, NY 11367-1597, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Bittman
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Science, University of Strathclyde, Glasgow G4 0RE, UK. Electronic address: n.j.pyne@strath.ac.uk.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Pyne
mesh_terms: D000818:Animals; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000378:metabolism; D005995:Glyceryl Ethers / Q000737:chemistry / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D008055:Lipids / Q000737:chemistry / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D013110:Sphingosine / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D020298:U937 Cells
chemical_list: D005995:Glyceryl Ethers; D053583:Interleukin-1beta; D008055:Lipids; D008070:Lipopolysaccharides; D013110:Sphingosine
keywords: Caspase-1; Ether glycerol lipids; Inflammasome; Interleukin-1; Multiple sclerosis; Sphingosine