Effects of thioredoxin on established airway remodeling in a chronic antigen exposure asthma model
Effects of thioredoxin on established airway remodeling in a chronic antigen exposure asthma model
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DOI：
10.1016/j.bbrc.2007.06.019
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发表时间：
2007-08-31
影响因子：
3.1
通讯作者：
Aizawa, Hisamichi
中科院分区：
文献类型：
--
作者：
Imaoka, Haruki;Hoshino, Tomoaki;Aizawa, Hisamichi
哮喘的发展和治疗仍然是医学界非常感兴趣的话题。以往的研究表明，细胞因子在哮喘的病理过程中起着重要作用。在这项研究中，我们研究了氧化还原活性蛋白硫氧还蛋白1(TRXI)是否可以预防卵清蛋白(OVA)驱动的慢性抗原暴露哮喘小鼠的呼吸道重构。将BALB/c小鼠致敏，然后用卵清蛋白(OVA)攻击9次(第19~45天)。在该方案中，在第34天时建立了气道重塑。在抗原攻击期间(第18-32天)给予重组人TRXI可显著抑制气道重塑、嗜酸性粒细胞炎症、气道高反应性，并导致肺组织嗜酸性粒细胞趋化因子、巨噬细胞炎性蛋白-1α和IL-13表达降低。慢性OVA暴露的Balb/c人TRXI转基因小鼠的气道重塑和嗜酸性肺炎症也得到了预防。重要的是，在建立气道重塑(35-45天)后，给予TRX1可改善气道病理。我们的结果表明，TRXI通过抑制肺内趋化因子和Th2细胞因子的产生，防止了气道重塑的发展，并改善了已建立的气道重塑。(C)2007 Elsevier Inc.保留所有权利。
The development and treatment of asthma remains a subject of considerable interest in the medical community. Previous studies implicate an important role of cytokines in the pathology of asthma. In this current study, we examined whether redox-active protein thioredoxin 1 (TRXI) could prevent airway remodeling in an ovalbumin (OVA)-driven mouse chronic antigen exposure asthma model. Balb/c mice were sensitized and then challenged nine times with OVA (days 19-45). In this protocol, airway remodeling was established by day 34. Administration of recombinant human TRXI during antigen challenge (days 18-32) significantly inhibited airway remodeling, eosinophilic pulmonary inflammation, airway hyperresponsiveness and resulted in decreased lung expression of eotaxin, macrophage inflammatory protein-la and IL-13. Airway remodeling and eosinophilic pulmonary inflammation was also prevented in chronic OVA-exposed Balb/c human TRXI transgenic mice. Importantly, TRX1-administration, after the establishment of airway remodeling (days 35-45), resulted in improved airway pathology. Our results suggest TRXI prevents the development of airway remodeling, and also improves established airway remodeling by inhibiting production of chemokines and Th2 cytokines in the lungs. (C) 2007 Elsevier Inc. All rights reserved.