title: Sphingosine-1-phosphate exhibits anti-proliferative and anti-inflammatory effects in mouse models of psoriasis.
abstract: BACKGROUND
  It has been indicated that the sphingolipid sphingosine-1-phosphate (S1P) restrains the ability of dendritic cells to migrate to lymph nodes. Furthermore S1P has been demonstrated to inhibit cell growth in human keratinocytes. However, only little is known about the effect of S1P in hyperproliferative and inflammatory in vivo models.
  
  
  OBJECTIVE
  In this study, locally acting S1P was explored in different experimental mouse models of psoriasis vulgaris.
  
  
  METHODS
  S1P and FTY720 were tested in the imiquimod-induced psoriasis mouse model, the mouse tail assay and a pilot study of the severe combined immunodeficiency mice (SCID).
  
  
  RESULTS
  In the imiquimod model the positive control diflorasone diacetate and S1P, but not FTY720 reduced the imiquimod-induced epidermal hyperproliferation of the ear skin. This effect was confirmed in the SCID model, where S1P treated skin from patients suffering from psoriasis showed a decrease in epidermal thickness compared to vehicle. In the imiquimod model, there was also significant inhibition of ear swelling and a moderate reduction of inflammatory cell influx and oedema formation in ear skin by S1P treatment. The inflammatory response on the back skin was, however, only reduced by diflorasone diacetate. In the mouse tail assay, the influence of S1P and FTY720 in stratum granulosum formation was tested compared to the positive control calcipotriol. Whereas topical administration of calcipotriol led to a low but significant increase of stratum granulosum, S1P and FTY720 lacked such an effect.
  
  
  CONCLUSIONS
  Taken together, these results imply that topical administration of S1P might be a new option for the treatment of mild to moderate psoriasis lesions.
authors: Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.
authors: Katrin
authors: K
authors: Schaper
authors: Jeannette
authors: J
authors: Dickhaut
authors: Lukasz
authors: L
authors: Japtok
authors: Manfred
authors: M
authors: Kietzmann
authors: Reinhard
authors: R
authors: Mischke
authors: Burkhard
authors: B
authors: Kleuser
authors: Wolfgang
authors: W
authors: Bäumer
mesh_terms: D000279:Administration, Cutaneous; D000634:Aminoquinolines; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001623:Betamethasone / Q000031:analogs & derivatives / Q000494:pharmacology; D002117:Calcitriol / Q000031:analogs & derivatives / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D000068876:Fingolimod Hydrochloride; D006801:Humans; D000077271:Imiquimod; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D023441:Local Lymph Node Assay; D008246:Lysophospholipids / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D011409:Propylene Glycols / Q000008:administration & dosage / Q000494:pharmacology*; D011565:Psoriasis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049349:Receptors, Lysosphingolipid / Q000187:drug effects / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016038:Skin Transplantation; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000081025:Sphingosine-1-Phosphate Receptors; D013997:Time Factors
chemical_list: D000634:Aminoquinolines; D000893:Anti-Inflammatory Agents; D003879:Dermatologic Agents; D008246:Lysophospholipids; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; C477362:S1PR1 protein, human; C556330:S1pr1 protein, mouse; D000081025:Sphingosine-1-Phosphate Receptors; C055085:calcipotriene; C060506:sphingosine 1-phosphate; D001623:Betamethasone; D002117:Calcitriol; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine; D000077271:Imiquimod; C014477:diflorasone