Sphingosine kinase 2 in autoimmune/inflammatory disease and development of sphingosine kinase 2 inhibitors

Nigel J. Pyne, David R. Adams, Susan Pyne

Research output: Contribution to journalLiterature review

10 Citations (Scopus)
17 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
Number of pages10
JournalTrends in Pharmacological Sciences
Volume38
Issue number7
Early online date9 Jun 2017
DOIs
Publication statusPublished - 31 Jul 2017

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Keywords

  • sphingosine kinase
  • autoimmune disease
  • interleukin
  • interferon-γ
  • histone deacetylase
  • retinoid-related orphan receptor-γt

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