Endogenous and Exogenous Thioredoxin 1 Prevents Goblet Cell Hyperplasia in a Chronic Antigen Exposure Asthma Model
Endogenous and Exogenous Thioredoxin 1 Prevents Goblet Cell Hyperplasia in a Chronic Antigen Exposure Asthma Model
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DOI：
10.2332/allergolint.09-oa-0086
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发表时间：
2009-09-01
影响因子：
6.8
通讯作者：
Aizawa, Hisamichi
中科院分区：
文献类型：
--
作者：
Imaoka, Haruki;Hoshino, Tomoaki;Aizawa, Hisamichi
背景：支气管哮喘伴粘液分泌增多的杯状细胞增生导致发病率和死亡率增高。我们报道了硫氧还蛋白1 (TRX1)，一种氧化还原（还原/氧化）活性蛋白，作为一种强抗氧化剂，抑制肺嗜酸性粒细胞炎症和肺趋化因子和Th2细胞因子的产生，从而减少小鼠哮喘模型中的气道高反应性（AHR）和气道重塑。在本研究中，我们研究了内源性或外源性TRX1是否抑制慢性暴露于抗原的小鼠哮喘模型中的杯状细胞增生。方法：我们使用Balb/c野生型小鼠和Balb/c背景的人TRX1转基因小鼠组成性地在肺中过量产生人TRX1蛋白。小鼠先致敏7次（第0 ~ 12天），然后用卵清蛋白（OVA）攻毒9次（第19 ~ 45天）。从第18 ~ 44天（14次）或第35 ~ 45天（6次），每隔2天给Balb/c小鼠注射40 μ g重组人TRX1 （rhTRX1）蛋白。第34天或第45天定量检测肺杯状细胞。结果：与TRX1基因阴性小鼠相比，TRX1基因转基因小鼠的杯状细胞增生明显受到抑制。在OVA致敏和OVA致敏的野生型小鼠中（第18 ~ 44天）给予rhTRX1可显著抑制杯状细胞增生。此外，在建立杯状细胞增生后（第35 ~ 45天）给予rhTRX1也能显著改善ova致敏和攻毒野生型小鼠的杯状细胞增生。结论：我们的研究结果表明TRX1可以阻止杯状细胞增生的发展，并改善已建立的杯状细胞增生。
Background: Goblet cell hyperplasia with mucus hypersecretion contribute to increased morbidity and mortality in bronchial asthma. We have reported that thioredoxin 1 (TRX1), a redox (reduction/oxidation)-active protein acting as a strong antioxidant, inhibits pulmonary eosinophilic inflammation and production of chemokines and Th2 cytokines in the lungs, thus decreasing airway hyperresponsiveness (AHR) and airway remodeling in mouse asthma models. In the present study, we investigated whether endogenous or exogenous TRX1 inhibits goblet cell hyperplasia in a mouse asthma model involving chronic exposure to antigen.Methods: We used wild-type Balb/c mice and Balb/c background human TRX1-transgenic mice constitutively overproducing human TRX1 protein in the lungs. Mice were sensitized 7 times (days 0 to 12) and then challenged 9 times with ovalbumin (OVA) (days 19 to 45). Every second day from days 18 to 44 (14 times) or days 35 to 45 (6 times), Balb/c mice were treated with 40 mu g recombinant human TRX1 (rhTRX1) protein. Goblet cells in the lungs were examined quantitatively on day 34 or 45.Results: Goblet cell hyperplasia was significantly prevented in TRX1-transgenic mice in comparison with TRX1 transgene-negative mice. rhTRX1 administration during OVA challenge (days 18 to 44) significantly inhibited goblet cell hyperplasia in OVA-sensitized and -challenged wild-type mice. Moreover, rhTRX1 administration after the establishment of goblet cell hyperplasia (days 35 to 45) also significantly ameliorated goblet cell hyperplasia in OVA-sensitized and -challenged wild-type mice.Conclusions: Our results suggest that TRX1 prevents the development of goblet cell hyperplasia, and also ameliorates established goblet cell hyperplasia.