title: Expression of the EP4 prostaglandin E2 receptor subtype with rat dextran sodium sulphate colitis: colitis suppression by a selective agonist, ONO-AE1-329.
abstract: Expression of the EP4 receptor, a prostaglandin (PG)E2 receptor subtype, as well as disease suppression by the administration of a selective EP4 agonist (ONO-AE1-329) was investigated in the colorectal mucosa of rats with dextran sodium sulphate (DSS)-induced colitis. Rats were given drinking water containing 3% DSS for 2 weeks. Expression of EP4 receptor mRNA was barely detectable under normal conditions according to reverse transcription-polymerase chain reaction (RT-PCR). By 1 week after the initial administration of DSS, the receptor mRNA was strongly expressed. After ONO-AE1-329 was administered intracolonically to rats with DSS colitis for 7 consecutive days, erosion and ulceration decreased. Peripheral white blood cell (WBC) counts became less elevated. Interleukin (IL)-1beta and growth-regulated gene product/cytokine-induced neutrophil chemoattractant (GRO/CINC-1) concentrations in colorectal mucosa were lower than in colitis control group (IL-1beta: 12.8 +/- 4.6 and 30.8 +/- 6.2 microg/mg protein, P < 0.05; GRO/CINC-1: 15.5 +/- 3.0 and 39.2 +/- 5.4 microg/mg protein, P < 0.05), and the expression of the corresponding cytokine mRNA was strongly suppressed. IL-10 concentration was higher than in control group (14.5 +/- 1.7 and 7.9 +/- 1.2 microg/mg, P < 0.05), and the mRNA was more strongly expressed. These results suggest that the EP4 receptor is important in colonic inflammation, and that PGE2 suppresses DSS colitis at least partly via the EP4 receptor and the above cytokine changes. Intracolonic administration of selective EP4 agonist might have therapeutic applicability in inflammatory bowel disease such as ulcerative colitis.
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, Japan. in2044@poh.osaka-med.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Nitta
authors.forename: I
authors.initials: I
authors.lastname: Hirata
authors.forename: K
authors.initials: K
authors.lastname: Toshina
authors.forename: M
authors.initials: M
authors.lastname: Murano
authors.forename: K
authors.initials: K
authors.lastname: Maemura
authors.forename: N
authors.initials: N
authors.lastname: Hamamoto
authors.forename: S
authors.initials: S
authors.lastname: Sasaki
authors.forename: H
authors.initials: H
authors.lastname: Yamauchi
authors.forename: K
authors.initials: K
authors.lastname: Katsu
mesh_terms: D000208:Acute Disease; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016466:CHO Cells; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003106:Colon / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D006224:Cricetinae; D016264:Dextran Sulfate / Q000009:adverse effects; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D007958:Leukocyte Count; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000235:genetics*; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013997:Time Factors
chemical_list: D000897:Anti-Ulcer Agents; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C513297:Cxcl1 protein, rat; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D008738:Methyl Ethers; C461399:ONO-AE1-329; C545646:Ptger2 protein, rat; C545652:Ptger4 protein, rat; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D016753:Interleukin-10; D016264:Dextran Sulfate; D009195:Peroxidase; D015232:Dinoprostone