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)
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)
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DOI：
10.1016/j.ejps.2013.04.017
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发表时间：
2013-06-14
影响因子：
4.6
通讯作者：
Hirayama, Yoshitaka
中科院分区：
文献类型：
--
作者：
Tasaki, Mamoru;Kobayashi, Miki;Hirayama, Yoshitaka
辅助性T细胞2型（CRTH2）上表达的趋化因子受体同源分子是在嗜酸性粒细胞、嗜碱性粒细胞和Th2型T细胞上发现的PGD（2）受体，其表现出趋化性并在激活级联中发挥作用。然而，尽管已知许多CRTH2拮抗剂（包括雷马曲班）在某些动物模型中发挥活性，但在EA诱导的气道高反应性的豚鼠模型中的活性尚未得到证实。新开发的CRTH2拮抗剂ASP 5642在先前的研究中显示出对人和豚鼠CRTH2的拮抗活性，并且还发现其在治疗豚鼠气道炎症和气道高反应性模型中有效。虽然以前的研究已经使用大鼠和小鼠等动物来评估CRTH2拮抗剂的作用，但我们是第一次尝试在豚鼠哮喘模型中评估CRTH2功能，这可能有助于评估该化合物在人类中的作用，考虑到两个物种之间的气道功能相当，本研究的这些数据有力地表明了ASP 5642在研究CRTH2在炎症反应中的作用以及作为人类哮喘的药物治疗中的效用。(c)2013爱思唯尔有限公司版权所有。
Chemoattractant receptor homologous molecule expressed on T helper type 2 cells (CRTH2) is a PGD(2) 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. (c) 2013 Elsevier B.V. All rights reserved.