title: Prostaglandin E receptor subtype EP3 in conjunctival epithelium regulates late-phase reaction of experimental allergic conjunctivitis.
abstract: BACKGROUND
  We previously demonstrated that the prostaglandin E(2) (PGE(2))-EP3 pathway negatively regulates allergic reactions in a murine allergic asthma model.
  
  
  OBJECTIVE
  We investigated whether the PGE(2)-EP3 pathway also regulates the development of murine experimental allergic conjunctivitis (EAC).
  
  
  METHODS
  The expression of EP3 was examined by means of RT-PCR and immunohistochemistry in wild-type mice, as well as by means of 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside staining in mice deficient in EP3 (Ptger3(-/-) mice) carrying the beta-galactosidase gene at the EP3 gene locus. EAC was induced by immunization of mice with short ragweed pollen (RW), followed by challenge with eye drops of RW, and eosinophil infiltration and eotaxin-1 mRNA expression in the conjunctiva were examined. Mice were also treated with a topical application of an EP3-selective agonist during the elicitation phase. Quantitative RT-PCR was used to detect expression of COXs and prostaglandin E synthases, and ELISA was used to measure PGE(2) production in the eyelid.
  
  
  RESULTS
  EP3 was constitutively expressed in conjunctival epithelium on the ocular surface. Ptger3(-/-) mice demonstrated significantly increased eosinophil infiltration in conjunctiva after RW challenge compared with wild-type mice. Consistently, significantly higher expression of eotaxin-1 mRNA was observed in Ptger3(-/-) mice. Conversely, treatment of wild-type mice with an EP3-selective agonist resulted in a significant decrease in eosinophil infiltration, which was blunted in Ptger3(-/-) mice. Expression of COX-2 and prostaglandin E synthases was upregulated and PGE(2) content was increased in the eyelids after RW challenge.
  
  
  CONCLUSIONS
  These data suggest that PGE(2) acts on EP3 in conjunctival epithelium and downregulates the progression of EAC.
authors.affiliation: Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ueta
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Matsuoka
authors.forename: Shuh
authors.initials: S
authors.lastname: Narumiya
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kinoshita
mesh_terms: D031164:Ambrosia / Q000276:immunology; D000818:Animals; D054413:Chemokine CCL11 / Q000378:metabolism; D003228:Conjunctiva / Q000276:immunology* / Q000473:pathology; D003233:Conjunctivitis, Allergic / Q000276:immunology* / Q000473:pathology; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D004848:Epithelium / Q000276:immunology / Q000473:pathology; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011058:Pollen / Q000276:immunology; D000071876:Prostaglandin-E Synthases; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D058308:Receptors, Prostaglandin E, EP3 Subtype; D015854:Up-Regulation / Q000276:immunology; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; C121546:ONO AE 248; C545648:Ptger3 protein, mouse; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; C077623:Ptgs2 protein, mouse; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D001616:beta-Galactosidase; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone