Effect of Y-27632 on release of cytokines from peripheral T cells in asthmatic patients and normal subjects

Effect of Y-27632 on release of cytokines from peripheral T cells in asthmatic patients and normal subjects
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DOI:
10.1016/j.intimp.2003.12.014
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发表时间:
2004-04-01
影响因子:
5.6
通讯作者:
Mori, M
Mori, M
中科院分区:
医学2区
文献类型:
--
作者:
Aihara, M;Dobashi, K;Mori, M

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此前我们曾报道,Y-27632 是 RhoA 的 Rho 相关蛋白激酶 (ROCK) 选择性抑制剂,可抑制正常人外周 T 细胞中刀豆球蛋白 A (Con A) 诱导的细胞因子分泌。最近的研究表明其可用于支气管哮喘的临床治疗。我们检查了 Y-27632 对哮喘患者 T 细胞释放细胞因子的影响。在 Y-27632 存在的情况下,用 Coll A 刺激六名哮喘受试者和六名正常人的外周 T 细胞 24 小时。测量上清液中IL-2、干扰素(IFN)-γ、IL-4和IL-5的浓度。 Y-27632 下调哮喘患者中 Con A 激活的 T 细胞 IL-2 和 IFN-γ 的分泌,并微弱地减少 IL-4 和 IL-5 的分泌。哮喘患者IFN-γ和IL-4分泌的减少程度低于正常人。我们的数据表明,支气管哮喘患者中 RhoA/ROCK 通路参与 TCR 介导的 IFN-γ 和 IL-4 分泌与健康人不同。 (C) 2004 Elsevier B.V. 保留所有权利。
Previously we have reported that Y-27632, a selective inhibitor of Rho-associated protein kinases (ROCKs) for RhoA, suppressed concanavalin A (Con A)-induced secretion of cytokines from peripheral T cells of normal persons. Recent studies suggested its usefulness for clinical management of bronchial asthma. We examined effect of Y-27632 on release of cytokines from T cells of asthmatic patients. Peripheral T cells of six asthmatic subjects and six normal persons were stimulated with Coll A for 24 h in the presence of Y-27632. The concentrations of IL-2, interferon (IFN)-gamma, IL-4, and IL-5 in supernatant were measured. Y-27632 down-regulated secretion of IL-2 and IFN-gamma and weakly decreased secretion of IL-4 and IL-5 from Con A-activated T cells in the asthmatics. The reduced secretion of IFN-gamma and IL-4 in the asthmatics was inferior to that in the normal subjects. Our data suggested that the involvement of RhoA/ROCK pathway in TCR-mediated secretion of IFN-gamma and IL-4 in patients with bronchial asthma differed from that in healthy persons. (C) 2004 Elsevier B.V. All rights reserved.