DP2 (CRTh2) antagonism reduces ocular inflammation induced by allergen challenge and respiratory syncytial virus
| Autor: | Daniel S. Lorrain, Yen Pham Truong, Sailen Barik, Brian Andrew Stearns, Jill Melissa Scott, Karin J. Stebbins, Hutchinson John H, Alexander Broadhead, Alla Musiyenko, Jilly F. Evans, Peppi Prasit |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Allergy Benzylamines Ovalbumin Administration Topical Immunology Guinea Pigs Receptors Prostaglandin Respiratory Syncytial Virus Infections Virus chemistry.chemical_compound Conjunctivitis Viral Mice Anti-Allergic Agents medicine Immunology and Allergy Ambrosia Animals Respiratory system Receptors Immunologic Conjunctivitis Allergic Mice Inbred BALB C biology General Medicine Allergens medicine.disease Allergic conjunctivitis Disease Models Animal chemistry biology.protein Female Prostaglandin D2 Interleukin-4 Antagonism |
| Zdroj: | International archives of allergy and immunology. 157(3) |
| ISSN: | 1423-0097 |
| Popis: | Background: Allergic conjunctivitis is characterized by itchy, watery and swollen eyes which occur in response to exposure to seasonal or environmental allergens. The early phase reaction of allergic conjunctivitis is primarily mediated by mast cell degranulation while the late phase reaction is driven by Th2 cells and eosinophils. Prostaglandin D2 (PGD2), released from mast cells, is present in allergic conjunctival tears and may elicit classical allergic responses via interaction with the high-affinity DP2 receptor (chemoattractant receptor-homologous molecule expressed on Th2 cells, CRTh2). Furthermore, antagonism of this receptor is well known to inhibit eosinophil chemotaxis, basophil activation and Th2 cytokine production. PGD2, therefore, may be involved in both early and late phase reactions in response to allergen challenge. Methods: Thus, we explored whether our novel and selective DP2 antagonist AM156 would be efficacious in animal models of allergic conjunctivitis. Furthermore, as respiratory syncytial virus (RSV) has been implicated in the pathogenesis of allergic conjunctivitis, we examined the effects of DP2 antagonism in a murine model of RSV ocular infection. Results: Utilizing a guinea pig ovalbumin model and a murine ragweed model we demonstrated that AM156 reduces redness, discharge and swelling in response to allergen challenge. These effects were equal to or greater than those of current clinical treatment options for allergic conjunctivitis including topical corticosteroids and a dual-mechanism antihistamine and decongestant. AM156 significantly reduced RSV-induced ocular inflammation and IL-4 production. Conclusion: These results suggest that a topical DP2 antagonist such as AM156 may represent a novel therapeutic for allergic conjunctivitis. |
| Databáze: | OpenAIRE |
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