Targeting S1P in Inflammatory Bowel Disease: New Avenues for Modulating Intestinal Leukocyte Migration

J Crohns Colitis. 2018 Aug 22;12(suppl_2):S678-S686. doi: 10.1093/ecco-jcc/jjx107.

Abstract

Sphingosine 1 phosphate [S1P] is a bioactive lipid mediator involved in the regulation of several cellular processes though the activation of a G protein-coupled receptor family known as the S1P receptors [S1PRs]. Advances in the understanding of the biological activities mediated by S1PRs have sparked great interest in the S1P/S1PRs axes as new therapeutic targets for the modulation of several cellular processes. In particular, the S1P/S1PR1 axis has been identified as key regulator for lymphocyte migration from lymph nodes. The blockade of this axis is emerging as a new therapeutic approach to control the aberrant leukocyte migration into the mucosa in inflammatory bowel disease [IBD]. This review briefly summarises the current evidence coming from clinical studies, and discusses the future prospects of S1P inhibitors for treatment of inflammatory bowel disease.

MeSH terms

  • Animals
  • Camphanes / therapeutic use
  • Cell Movement / drug effects
  • Fingolimod Hydrochloride / therapeutic use
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Indans / therapeutic use
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / immunology
  • Leukocytes / physiology
  • Lysophospholipids / antagonists & inhibitors*
  • Lysophospholipids / metabolism
  • Molecular Targeted Therapy
  • Oxadiazoles / therapeutic use
  • Receptors, Lysosphingolipid / metabolism
  • Signal Transduction
  • Sphingosine / analogs & derivatives*
  • Sphingosine / antagonists & inhibitors
  • Sphingosine / metabolism
  • Sulfhydryl Compounds / therapeutic use
  • Sulfonamides / therapeutic use

Substances

  • Camphanes
  • Immunosuppressive Agents
  • Indans
  • KRP-203
  • Lysophospholipids
  • N,N-dicyclohexyl-isoborneol-10-sulfonamide
  • Oxadiazoles
  • Receptors, Lysosphingolipid
  • Sulfhydryl Compounds
  • Sulfonamides
  • sphingosine 1-phosphate
  • Fingolimod Hydrochloride
  • Sphingosine
  • ozanimod