Objectives

Chronic obstructive pulmonary disease (COPD) is a major cause of death globally. Inflammation plays a crucial role in COPD development. Pyroptosis, an inflammatory form of cell death, may involve in the pathogenesis of COPD. This study aims to explore the role and action mechanism of triggering receptor expressed on myeloid cells 1 (TREM-1) in COPD.

Methods

Here, cigarette smoke stimulation was used to establish COPD model in mice. Cigarette smoke extract combined with lipopolysaccharide was used to stimulate RAW264.7 cells for COPD model in vitro. QRT-PCR and Western blot were performed to detect the expression of mRNA and proteins, respectively, in the lung tissues and cells. Concentration of cytokines was measured using ELISA. H&E staining was used to analyze the pathological changes in lung tissues. The number of infiltrated macrophage was examined using immunofluorescence. LP17 was used to silence the expression of TREM-1.

Results

The results showed that TREM-1 was highly expressed in COPD. In vivo, inhibition of TREM-1 effectively improved the injury in lung tissues of COPD mouse, and reduced the infiltration of macrophages. Moreover, inhibition of TREM-1 in vivo and in vitro notably suppressed the activation of NLRP3 inflammasome and pyroptosis. Rescue experiment demonstrated that TREM-1 activated pyroptosis via regulating NLRP3 inflammasome.

Conclusion

Overall, our results proved that TREM-1 promoted the lung injury and inflammation in COPD mouse through activation of NLRP3 inflammasome-mediated pyroptosis. Our data indicated a novel mechanism of TREM-1 in COPD development, and maybe provide a novel therapeutic target for COPD treatment.

中文翻译：

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TREM-1通过激活NLRP3炎性体介导的细胞焦亡加重慢性阻塞性肺疾病的发展

目标

慢性阻塞性肺病（COPD）是全球主要的死亡原因。炎症在慢性阻塞性肺病的发展中起着至关重要的作用。焦亡是细胞死亡的一种炎症形式，可能与 COPD 的发病机制有关。本研究旨在探讨触发受体表达于骨髓细胞1（TREM-1）在COPD中的作用和作用机制。

方法

在这里，香烟烟雾刺激被用来建立小鼠慢性阻塞性肺病模型。香烟烟雾提取物联合脂多糖用于体外刺激COPD模型的RAW264.7细胞。采用 QRT-PCR 和 Western blot 分别检测肺组织和细胞中 mRNA 和蛋白质的表达。使用ELISA测量细胞因子的浓度。H&E染色用于分析肺组织的病理变化。使用免疫荧光检查浸润的巨噬细胞的数量。LP17 用于沉默 TREM-1 的表达。

结果

结果表明TREM-1在COPD中高表达。在体内，抑制TREM-1有效改善COPD小鼠肺组织损伤，减少巨噬细胞浸润。此外，在体内和体外抑制 TREM-1 显着抑制了 NLRP3 炎性体的激活和细胞焦亡。救援实验表明，TREM-1通过调节NLRP3炎性体激活细胞焦亡。

结论

总体而言，我们的结果证明 TREM-1 通过激活 NLRP3 炎性体介导的细胞焦亡促进了 COPD 小鼠的肺损伤和炎症。我们的数据表明 TREM-1 在 COPD 发展中的新机制，可能为 COPD 治疗提供新的治疗靶点。