title: Sphingosylphosphorylcholine reduces the organ injury/dysfunction and inflammation caused by endotoxemia in the rat.
abstract: OBJECTIVE
  Sphingosylphosphorylcholine (SPC) has been reported to activate a variety of G-protein coupled receptors, including S1P(1-5), G2A, GPR4, and OGR1 (GPR68). Interestingly, other structurally related lysophospholipid agonists of these receptors have been shown to exhibit immunomodulatory properties both in vitro and in vivo. These include prevention of tumor necrosis factor-alpha-induced monocyte adhesion to aortic endothelium in mice (sphingosine-1-phosphate via S1P(1-5) receptors) and reduction of organ injury and/or mortality in animal models of sepsis and endotoxemia (lysophosphatidylcholine via G2A). Here, we investigate the effects of SPC on the organ injury/dysfunction caused by systemic administration of lipopolysaccharide and the mechanisms underlying the observed effects of SPC.
  
  
  METHODS
  Prospective, randomized study.
  
  
  METHODS
  University-based research laboratory.
  
  
  METHODS
  Sixty-one anesthetized male Wistar rats.
  
  
  METHODS
  Rats received either SPC (10 mg/kg intravenously) or vehicle (phosphate-buffered saline 1 mL/kg intravenously) 15 mins before or 15 mins after induction of endotoxemia with lipopolysaccharide (6 mg/kg intravenously).
  
  
  RESULTS
  Treatment with SPC significantly reduced the organ/dysfunction injury caused by lipopolysaccharide. SPC pretreatment significantly reduced the circulating levels of interleukin-1beta and interleukin-6, the expression of CD11b (ligand for intercellular adhesion molecule-1) on circulating polymorphonuclear cells, the expression of proteins of intercellular adhesion molecule-1 (Western blot and immunohistochemistry), cyclooxygenase-2 and nuclear translocation of nuclear factor-kappaB (Western blot analysis), and inducible nitric oxide synthase (immunohistochemistry) as well as the lung injury caused by endotoxemia in the rat.
  
  
  CONCLUSIONS
  SPC reduced the organ injury/dysfunction caused by endotoxin in the rat. These beneficial effects of SPC are associated with potent anti-inflammatory effects.
authors.affiliation: Centre for Translational Medicine and Therapeutics, The William Harvey Research Institute, St. Bartholomew's and The Royal London School of Medicine and Dentistry, Queen Mary, University of London, Charterhouse Square, London, United Kingdom.
authors.forename: Oliver
authors.initials: O
authors.lastname: Murch
authors.forename: Maha
authors.initials: M
authors.lastname: Abdelrahman
authors.forename: Massimo
authors.initials: M
authors.lastname: Collino
authors.forename: Margherita
authors.initials: M
authors.lastname: Gallicchio
authors.forename: Elisa
authors.initials: E
authors.lastname: Benetti
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
authors.forename: Roberto
authors.initials: R
authors.lastname: Fantozzi
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
authors.forename: Christoph
authors.initials: C
authors.lastname: Thiemermann
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004334:Drug Administration Schedule; D019446:Endotoxemia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008168:Lung / Q000201:enzymology / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D016207:Cytokines; D016328:NF-kappa B; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D013110:Sphingosine