BACKGROUND Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is life-threatening. Several serum biomarkers, such as Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D), are clinically used for evaluating AE-IPF, but these biomarkers are not adequate for establishing an early and accurate diagnosis of AE-IPF. Recently, the protective roles of the members of the peroxiredoxin (PRDX) family have been reported in IPF; however, the role of PRDX4 in AE-IPF is unclear. METHODS Serum levels of PRDX4 protein, KL-6, SP-D and lactate dehydrogenase (LDH) in 51 patients with stable IPF (S-IPF), 38 patients with AE-IPF and 15 healthy volunteers were retrospectively assessed using enzyme-linked immunosorbent assay. Moreover, as an animal model of pulmonary fibrosis, wild-type (WT) and PRDX4-transgenic (Tg) mice were intratracheally administered with bleomycin (BLM, 2 mg/kg), and fibrotic and inflammatory changes in lungs were evaluated 3 weeks after the intratracheal administration. RESULTS Serum levels of PRDX4 protein, KL-6, SP-D and LDH in patients with S-IPF and AE-IPF were significantly higher than those in healthy volunteers, and those in AE-IPF patients were the highest among the three groups. Using receiver operating characteristic curves, area under the curve values of serum PRDX4 protein, KL-6, SP-D, and LDH for detecting AE-IPF were 0.873, 0.698, 0.675, and 0.906, respectively. BLM-treated Tg mice demonstrated aggravated histopathological findings and poor prognosis compared with BLM-treated WT mice. Moreover, PRDX4 expression was observed in alveolar macrophages and lung epithelial cells of BLM-treated Tg mice. CONCLUSIONS PRDX4 is associated with the aggravation of inflammatory changes and fibrosis in the pathogenesis of IPF, and serum PRDX4 may be useful in clinical practice of IPF patients.

中文翻译：

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peroxiredoxin-4的过表达影响特发性肺纤维化的进程。

背景技术特发性肺纤维化（AE-IPF）的急性加重威胁生命。几种血清生物标记物，例如Krebs von den Lungen-6（KL-6）和表面活性剂蛋白D（SP-D），已在临床上用于评估AE-IPF，但这些生物标记物不足以建立早期和准确的诊断AE-IPF。 AE-IPF。最近，在IPF中已经报道了过氧化物酶（PRDX）家族成员的保护作用。但是，尚不清楚PRDX4在AE-IPF中的作用。方法采用酶联免疫吸附剂回顾性评估51例稳定IPF（S-IPF），38例AE-IPF和15名健康志愿者的血清PRDX4蛋白，KL-6，SP-D和乳酸脱氢酶（LDH）水平。分析。此外，作为肺纤维化的动物模型，气管内给予博来霉素（BLM，2 mg / kg）对野生型（WT）和PRDX4转基因（Tg）小鼠进行气管内给药，气管内给药3周后评估肺中的纤维化和炎症变化。结果S-IPF和AE-IPF患者的血清PRDX4蛋白，KL-6，SP-D和LDH水平明显高于健康志愿者，而AE-IPF患者的血清中PRDX4蛋白，KL-6，SP-D和LDH水平显着高于健康志愿者。使用接收器工作特征曲线，用于检测AE-IPF的血清PRDX4蛋白，KL-6，SP-D和LDH的曲线值下面积分别为0.873、0.698、0.675和0.906。与BLM治疗的WT小鼠相比，BLM治疗的Tg小鼠表现出更为严重的组织病理学发现和不良预后。而且，在BLM治疗的Tg小鼠的肺泡巨噬细胞和肺上皮细胞中观察到PRDX4表达。结论PRDX4与IPF发病机制中炎症变化和纤维化的加剧有关，血清PRDX4在IPF患者的临床实践中可能有用。