title: Sphingosine-1-Phosphate Signaling in Inflammatory Bowel Disease.
abstract: An unmet medical need exists for the development of targeted therapies for the treatment of inflammatory bowel disease (IBD) with easily administered and stable oral drugs, particularly as most patients on biologics [i.e., tumor necrosis factor (TNF) inhibitors and anti-integrins] are either primary non-responders or lose responsiveness during maintenance treatment. A new class of small molecules, sphingosine-1-phosphate (S1P) receptor modulators, has recently shown efficacy in IBD. Here we provide an overview of the mechanism of action of this novel treatment principle in the context of intestinal inflammation. The remarkable impact of therapeutic modulation of the S1P/S1P receptor axis reflects the complexity of the pathogenesis of IBD and the fact that S1P receptor modulation may be a logical therapeutic approach for the future management of IBD.
authors.affiliation: Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark. Electronic address: ole.haagen.nielsen@regionh.dk.
authors.forename: Ole Haagen
authors.initials: OH
authors.lastname: Nielsen
authors.affiliation: Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, Copenhagen, Denmark; Immunology Section, Lund University, Lund, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Johansson-Lindbom
authors.affiliation: Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark; The Bioinformatics Centre, Department of Biology and Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Coskun
mesh_terms: D000818:Animals; D055808:Drug Discovery; D006801:Humans; D007189:Indans / Q000737:chemistry / Q000627:therapeutic use; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D010069:Oxadiazoles / Q000737:chemistry / Q000627:therapeutic use; D049349:Receptors, Lysosphingolipid / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D054852:Small Molecule Libraries / Q000737:chemistry / Q000627:therapeutic use*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D007189:Indans; D008246:Lysophospholipids; D010069:Oxadiazoles; D049349:Receptors, Lysosphingolipid; D054852:Small Molecule Libraries; C060506:sphingosine 1-phosphate; D013110:Sphingosine; C000607776:ozanimod
keywords: inflammatory bowel disease; receptor modulators; small molecules; sphingosine-1-phosphate; therapy