title: Suppression of acute rejection by administration of prostaglandin E2 receptor subtype 4 agonist in rat organ transplantation models.
abstract: BACKGROUND
  Prostaglandin E2 (PGE2) receptor subtype 4 (EP4) signaling is known to modulate the inflammation process. Several studies have demonstrated the potential utility of EP4-selective agonists for the management of autoimmune and inflammatory diseases. In the present study, we assessed the immunosuppressive efficacy of a selective EP4 agonist in experimental rat organ transplantation models.
  
  
  METHODS
  We continuously injected a selective EP4 agonist (CAY10580) by subcutaneous insertion of infuser pumps into recipient rats that underwent heterotopic heart and small bowel transplantation.
  
  
  RESULTS
  The administration of EP4 agonist significantly delayed cardiac allograft survival and delayed the onset of rejection in both the cardiac and intestinal allografts. Expression of proinflammatory cytokines of interferon-gamma was suppressed by the treatment compared with the vehicle-treated group. Furthermore, the expression of suppressor of cytokine signaling-1, a known intracellular regulation factor of IFN-gamma, was also down-regulated compared with the control group.
  
  
  CONCLUSIONS
  These results suggest that selective EP4 agonists represent a novel class of immune-modulator drugs that could be useful for the management of acute allogeneic rejection.
authors.affiliation: Department of Surgery (Hepato-pancreatico-biliary and Transplantation), Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Okamoto
authors.forename: Shinya
authors.initials: S
authors.lastname: Okamoto
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujimoto
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
mesh_terms: D000818:Animals; D015232:Dinoprostone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D015536:Down-Regulation; D006084:Graft Rejection / Q000378:metabolism / Q000517:prevention & control*; D016027:Heart Transplantation; D055104:Infusions, Subcutaneous; D007371:Interferon-gamma / Q000378:metabolism; D007421:Intestine, Small / Q000637:transplantation*; D008297:Male; D023421:Models, Animal; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000819:agonists*; D015398:Signal Transduction / Q000187:drug effects; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: C561931:CAY 10580; D011760:Pyrrolidinones; D058309:Receptors, Prostaglandin E, EP4 Subtype; C491589:Socs1 protein, rat; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D007371:Interferon-gamma; D015232:Dinoprostone
keywords: Acute rejection; Heart transplantation; Inflammation; Interferon-gamma; Prostaglandin E(2) receptor subtype 4 agonist; Small bowel transplantation