Sphingosine Kinase 2 in Autoimmune/Inflammatory Disease and the Development of Sphingosine Kinase 2 Inhibitors

Nigel J. Pyne, David Roger Adams, Susan Pyne

Research output: Contribution to journalArticle

15 Citations (Scopus)
23 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)581-591
JournalTrends in Pharmacological Sciences
Volume38
Issue number7
Early online date9 Jun 2017
DOIs
Publication statusPublished - Jul 2017

Keywords

  • Journal Article
  • Review

Fingerprint Dive into the research topics of 'Sphingosine Kinase 2 in Autoimmune/Inflammatory Disease and the Development of Sphingosine Kinase 2 Inhibitors'. Together they form a unique fingerprint.

Cite this