Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 123, Issue 2, Pages 466-471Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2008.09.044
Keywords
Conjunctival epithelium; prostaglandin E receptor subtype EP3; allergic conjunctivitis; eosinophilic conjunctival inflammation; EP3 agonist
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Funding
- Japanese Ministry of Health, Labour, and Welfare
- Japanese Ministry of Education, Culture, Sports, Science, and Technology
- JST
- Kyoto Foundation for the Promotion of Medical Science
- National Institute of Biomedical Innovation of Japan
- Intramural Research Fund of Kyoto Prefectural University of Medicine
- Takeda Scientific Foundation
- ONO Research Foundation
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Background: We previously demonstrated that the prostaglandin E-2 (PGE(2))-EP3 pathway negatively regulates allergic reactions in a murine allergic asthma model. Objectives: 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 RTPCR 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 R-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. Conclusion: These data suggest that PGE(2) acts on EP3 in conjunctival epithelium and downregulates the progression of EAC. (J Allergy Clin Immunol 2009;123:466-71.)
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