Thioredoxin-1 ameliorates cigarette smoke-induced lung inflammation and emphysema in mice
Thioredoxin-1 ameliorates cigarette smoke-induced lung inflammation and emphysema in mice
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DOI：
10.1124/jpet.107.134007
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发表时间：
2008-05-01
影响因子：
3.5
通讯作者：
Yodoi, Junji
中科院分区：
文献类型：
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作者：
Sato, Atsuyasu;Hoshino, Yuma;Yodoi, Junji
吸烟与炎症性肺部疾病的发展有关，炎症性肺部疾病是全世界主要的健康问题。我们假设，氧化还原调节分子硫氧还蛋白-1 (TRX) 具有抗炎、抗氧化和抗细胞凋亡作用，可以由香烟烟雾 (CS) 诱导，并有助于防止 CS 引起的炎症和肺部破坏。在一项急性研究中，人类 TRX 转基因小鼠和 C57BL6/J 小鼠暴露于主流 CS 3 天。在CS暴露小鼠的肺部，观察到支气管上皮损伤和支气管肺泡灌洗中性粒细胞增多。氧化应激和细胞凋亡增强，细胞因子巨噬细胞炎症蛋白2和肿瘤坏死因子(TNF)-α的表达分别增加15.3倍和2.4倍。与C57BL6/J小鼠相比，TRX转基因小鼠的炎症、氧化损伤和细胞凋亡明显减少，基质金属蛋白酶12 mRNA和血清TNF-α水平降低。当重组人TRX（40μg/体/天，3天）腹膜内注射时。在暴露于 CS 的 C57BL6/J 小鼠中，通过抑制中性粒细胞流入，观察到对 CS 引起的肺损伤提供显着的保护作用。在长期研究中，TRX转基因小鼠和C57BL6/J小鼠暴露于CS 6个月。这种慢性暴露导致 C57BL6/J 小鼠发生肺气肿，并伴有巨噬细胞和中性粒细胞显着浸润至肺部。这些病理变化在 TRX 转基因小鼠中得到显着抑制。总之，TRX 诱导改善了 CS 诱导的小鼠肺部炎症和肺气肿。因此，TRX-1可能在慢性阻塞性肺病等肺部炎症性疾病中发挥预防或治疗作用。
Cigarette smoking is associated with the development of inflammatory lung diseases representing major health problems worldwide. We hypothesized that the redox-regulating molecule thioredoxin-1 ( TRX), which shows anti-inflammatory, antioxidative, and antiapoptotic effects, could be induced by cigarette smoke ( CS) and contribute to protect against CS-induced inflammation and lung destruction. In an acute study, human TRX transgenic mice and C57BL6/J mice were exposed to mainstream CS for 3 days. In the lungs of CS-exposed mice, bronchial epithelial injury and bronchoalveolar lavage neutrophilia were observed. Oxidative stress and apoptosis were enhanced, and the expression of cytokines macrophage inflammatory protein-2 and tumor necrosis factor (TNF)-alpha was increased 15.3- and 2.4fold, respectively. Compared with C57BL6/J mice, TRX- transgenic mice had significantly less inflammation, oxidative damage and apoptosis, as well as decreased levels of matrix metalloprotease-12 mRNA and serum TNF-alpha. When recombinant human TRX ( 40 mu g/body/day, 3 days) was injected i.p. into CS-exposed C57BL6/J mice, a significant effect to offer protection against CS-induced lung injury was observed through suppression of neutrophil influx. In the chronic study, TRXtransgenic mice and C57BL6/J mice were exposed to CS for 6 months. This chronic exposure caused pulmonary emphysema in C57BL6/J mice accompanying prominent infiltration of macrophages and neutrophils to lung. These pathological changes were significantly suppressed in TRX-transgenic mice. In conclusion, TRX induction ameliorated CS-induced lung inflammation and emphysema in mice. TRX-1 may therefore play a preventive or therapeutic role in lung inflammatory disorders such as chronic obstructive pulmonary disease.