51. Inhibition of antigen-induced airway inflammation and hyperresponsiveness in guinea pigs by a selective antagonist of "chemoattractant receptor homologous molecule expressed on Th2 cells" (CRTH2).
- Author
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Tasaki M, Kobayashi M, Tenda Y, Tsujimoto S, Nakazato S, Numazaki M, Hirano Y, Matsuda H, Terasaka T, Miyao Y, Shimizu Y, and Hirayama Y
- Subjects
- Animals, Anti-Asthmatic Agents pharmacology, Anti-Inflammatory Agents pharmacology, Antigens, Benzhydryl Compounds pharmacology, Bronchial Hyperreactivity immunology, Bronchoalveolar Lavage Fluid cytology, Carbazoles therapeutic use, Cell Count, Eosinophilia chemically induced, Eosinophilia drug therapy, Guinea Pigs, HEK293 Cells, Humans, K562 Cells, Male, Ovalbumin, Pneumonia immunology, Prostaglandin D2, Pyridazines pharmacology, Sulfonamides therapeutic use, Anti-Asthmatic Agents therapeutic use, Anti-Inflammatory Agents therapeutic use, Benzhydryl Compounds therapeutic use, Bronchial Hyperreactivity drug therapy, Pneumonia drug therapy, Pyridazines therapeutic use, Receptors, Immunologic antagonists & inhibitors, Receptors, Prostaglandin antagonists & inhibitors
- Abstract
Chemoattractant receptor homologous molecule expressed on T helper type 2 cells (CRTH2) is a PGD2 receptor found on eosinophils, basophils, and Th2 type T cells which exhibits chemotaxis and functions in activation cascades. However, while a number of CRTH2 antagonists, including ramatroban, are known to exert activity in certain animal models, activity in a guinea pig model of EA-induced airway hyperresponsiveness has not been demonstrated. The newly developed CRTH2 antagonist ASP5642 has shown antagonistic activity against human and guinea pig CRTH2 in previous studies and has also been found effective in treating guinea pig models of airway inflammation and airway hyperresponsiveness. While previous studies have used animals such as rats and mice to evaluate CRTH2 antagonist effects, ours is the first attempt to evaluate CRTH2 function in a guinea pig asthma model, which may prove useful in evaluating the compound's effects in humans, given the comparable airway function between the two species taken together, these data from the present study strongly suggest the utility of ASP5642 in investigating the role of CRTH2 in inflammatory responses and as a drug treatment for human asthma., (Copyright © 2013 Elsevier B.V. All rights reserved.)
- Published
- 2013
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