Picture of virus

Open Access research that helps to deliver "better medicines"...

Strathprints makes available scholarly Open Access content by the Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS), a major research centre in Scotland and amongst the UK's top schools of pharmacy.

Research at SIPBS includes the "New medicines", "Better medicines" and "Better use of medicines" research groups. Together their research explores multidisciplinary approaches to improve understanding of fundamental bioscience and identify novel therapeutic targets with the aim of developing therapeutic interventions, investigation of the development and manufacture of drug substances and products, and harnessing Scotland's rich health informatics datasets to inform stratified medicine approaches and investigate the impact of public health interventions.

Explore Open Access research by SIPBS. Or explore all of Strathclyde's Open Access research...

Strathprints

Effect of sphingosine kinase modulators on interleukin-1β release, sphingosine 1-phosphate receptor 1 expression and experimental autoimmune encephalomyelitis : FTY720 analogues and inflammation

Barbour, Mark and McNaughton, Melissa and Boomkamp, Stephanie D. and MacRitchie, Neil and Jiang, Hui-Rong and Pyne, Nigel J and Pyne, Susan (2017) Effect of sphingosine kinase modulators on interleukin-1β release, sphingosine 1-phosphate receptor 1 expression and experimental autoimmune encephalomyelitis : FTY720 analogues and inflammation. British Journal of Pharmacology, 174 (2). pp. 210-222. ISSN 1476-5381

[img]
Preview
 Text (Barbour-etal-BJP2016-Effect-of-sphingosine-kinase-modulators-on-interleukin-1β-release)
Barbour_etal_BJP2016_Effect_of_sphingosine_kinase_modulators_on_interleukin_1_release.pdf
Accepted Author Manuscript
Download (915kB) | Preview

Abstract

Background and Purpose: The sphingosine analogue, FTY720 (Gilenya®) alleviates clinical disease progression in multiple sclerosis. Here we variously assessed the effects of an azide analogue of (S)-FTY720 vinylphosphonate (compound 5; a sphingosine kinase 1 activator), (R)-FTY720 methyl ether (ROMe, a sphingosine kinase 2 inhibitor) and RB-020 (a sphingosine kinase 1 inhibitor and sphingosine kinase 2 substrate) on IL-1beta formation, sphingosine 1-phosphate levels and S1P1 expression. We also assessed the effect of compound 5 and ROMe in an experimental autoimmune encephalomyelitis (EAE) model. Experimental Approach: We measured IL-1beta formation by macrophages, sphingosine 1-phosphate levels and S1P1 expression levels in vitro and clinical score and inflammatory cell infiltration into the spinal cord in vivo. Key Results: Treatment of differentiated U937 macrophages with compound 5, RB-020 or sphingosine (but not ROMe) enhanced IL-1beta release. This data suggests these compounds might be pro-inflammatory in vitro. However, compound 5 or ROMe reduced disease progression and infiltration of inflammatory cells into the spinal cord in EAE and ROMe induced a reduction in CD4+ and CD8+ T-cell levels in the blood (lymphopenia). Indeed, ROMe induced a marked decrease in cell surface S1P1 expression in vitro. Conclusion and Implications: This is the first demonstration that an activator of SK1 (compound 5) and an inhibitor of SK2 (ROMe, which also reduces cell surface S1P1 expression) have an anti-inflammatory action in EAE.

Item type: Article
ID code: 58650
Notes: This is the peer reviewed version of the following article: Barbour, M., McNaughton, M., Boomkamp, S. D., MacRitchie, N., Jiang, H-R., Pyne, N., & Pyne, S. (2016). Effect of sphingosine kinase modulators on interleukin-1β release, sphingosine 1-phosphate receptor 1 expression and experimental autoimmune encephalomyelitis: FTY720 analogues and inflammation. British Journal of Pharmacology, which has been published in final form at https://doi.org/10.1111/bph.13670. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Keywords: Sphingosine kinase, sphingosine 1-phosphate, inflammasome, multiple sclerosis, experimental autoimmune encephalomyelitis, autoimmune inflammatory demyelinating disease, T-lymphocytes, pathogen-associated molecular patterns, Immunology, Internal medicine, Immunology, Immunology and Allergy
Subjects: Science > Microbiology > Immunology
Medicine > Internal medicine
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Depositing user: Pure Administrator
Date deposited: 15 Nov 2016 11:29
Last modified: 11 Mar 2018 00:51
Related URLs:
URI: https://strathprints.strath.ac.uk/id/eprint/58650
Export data:
CORE (COnnecting REpositories)