Sphingosine kinase 2 in autoimmune/inflammatory disease and development of sphingosine kinase 2 inhibitors
Pyne, Nigel J. and Adams, David R. and Pyne, Susan (2017) Sphingosine kinase 2 in autoimmune/inflammatory disease and development of sphingosine kinase 2 inhibitors. Trends in Pharmacological Sciences, 38 (7). pp. 581-591. ISSN 0165-6147
|
Text (Pyne-etal-TPS2017-Sphingosine-kinase-2-in-autoimmune-inflammatory-disease)
Pyne_etal_TPS2017_Sphingosine_kinase_2_in_autoimmune_inflammatory_disease.pdf Accepted Author Manuscript License: ![]() Download (1MB)| Preview |
Abstract
The purpose of this Opinion is to present a case for targeting sphingosine kinase 2 (SK2) in autoimmune/inflammatory disease. Data obtained using Sphk2-/- mice suggest that SK2 is an anti-inflammatory enzyme, although this might be misleading because of a compensatory increase in the expression of a second isoform, sphingosine kinase 1 (SK1), which functions as a proinflammatory enzyme. SK2 is involved in regulating interleukin (IL)-12/interferon gamma (IFN-γ) and histone deacetylase-1/2 (HDAC-1/2) signalling and, potentially, retinoid-related orphan receptor gamma t (ROR-γt) stability linked with T helper (Th) 17 cell polarisation. Therefore, there is a need to develop highly potent SK2 inhibitors with selectivity over SK1 to clearly define the role of SK2 in autoimmune/inflammatory disease. Structural determinants of SK2 relative to SK1 will enable the design of selective SK2 inhibitors.
Creators(s): |
Pyne, Nigel J. ![]() ![]() | Item type: | Article |
---|---|
ID code: | 61548 |
Keywords: | sphingosine kinase, autoimmune disease, interleukin, interferon-γ, histone deacetylase, retinoid-related orphan receptor-γt, Therapeutics. Pharmacology, Toxicology, Pharmacology |
Subjects: | Medicine > Therapeutics. Pharmacology |
Department: | Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences |
Depositing user: | Pure Administrator |
Date deposited: | 10 Aug 2017 14:01 |
Last modified: | 22 Jan 2021 03:57 |
Related URLs: | |
URI: | https://strathprints.strath.ac.uk/id/eprint/61548 |
Export data: |