Thioredoxin reduces C-C chemokine-induced chemotaxis of human eosinophils
Thioredoxin reduces C-C chemokine-induced chemotaxis of human eosinophils
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DOI：
10.1111/j.1398-9995.2009.01969.x
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发表时间：
2009-08-01
期刊：
影响因子：
12.4
通讯作者：
Chihara, J.
中科院分区：
文献类型：
--
作者：
Kobayashi, N.;Yamada, Y.;Chihara, J.
背景：人硫氧还蛋白（TRX）是一种具有氧化还原活性的蛋白质，参与反应性氧化代谢。在最近的研究中，我们发现哮喘患者血清中TRX的水平升高，然而，TRX在过敏性炎症中的生理作用，包括嗜酸性粒细胞的浸润，还知之甚少。目的：在本研究中，我们检测TRX是否调节C-C趋化因子诱导的人嗜酸性粒细胞的趋化性。通过改良的CD 16阴性选择从轻度嗜酸性粒细胞增多的受试者中分离嗜酸性粒细胞。结果：TRX预孵育抑制了嗜酸性粒细胞趋化因子（eotaxin）诱导的嗜酸性粒细胞的趋化性，并对活化的正常T细胞表达和分泌的（RANTES）进行了调节。虽然TRX对C-C趋化因子受体3（Eotaxin和RANTES的受体）的表达没有影响，但我们证明了细胞外信号调节激酶1/2和p38丝裂原活化蛋白激酶的激活，它们在嗜酸性粒细胞迁移中起重要作用，通过TRX治疗减弱。我们的研究结果表明，引发TRX是有益的，以减少过敏性炎症通过负调节嗜酸性粒细胞的功能，并在治疗过敏性疾病，如哮喘的潜力。
Background: Human thioredoxin (TRX) is one of redox-active proteins that regulate reactive oxidative metabolisms. In recent study, we found that serum levels of TRX were elevated in asthmatic patients with exacerbation; however, few details are known about the physiological role of TRX in allergic inflammation, involving eosinophil infiltration.Objective: In the present study, we examined whether TRX modulated C-C chemokine-induced chemotaxis of human eosinophils.Methods: Eosinophils were isolated from subjects with mild eosinophilia by modified CD16 negative selection. After incubation with or without recombinant TRX, chemotaxis of human eosinophils was measured using Boyden chamber.Results: Preincubation with TRX suppressed eotaxin- and regulated on activation, normal T-cell expressed and secreted (RANTES)-induced chemotaxis of eosinophils. Although, TRX had no effect on the expression of C-C chemokine receptor 3, which is a receptor of eotaxin and RANTES, we demonstrated that the activation of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinases, which play an important role in eosinophil migration, was attenuated by the treatment with TRX.Conclusion: Our results suggest that the elicited TRX is beneficial to reduce allergic inflammation through negative regulation of eosinophil functions and has potential in the treatment of allergic diseases, such as asthma.