Complications arise in chronic obstructive pulmonary diseases (COPD) with excessive mucus production, especially during the exacerbation period, which contributes to airway blockage and bacterial infection. Neutrophil elastase (NE) is detected at high levels in airway secretions, and is the primary inducer of mucin production. Understanding the mechanism of NE-induced overproduction of mucin may lead to new therapies for COPD. It is known that activation of epidermal growth factor receptor (EGFR) and its downstream signaling cascade are involved in mucin production. However, the mechanism of NE-induced EGFR activation remains unclear. Tumor necrosis factor-α-converting enzyme (TACE) cleaves pro-transforming growth factor (TGF)-α in airway epithelial cells to release the mature, soluble TGF-α form, which subsequently binds to and activates EGFR. In this investigation, we demonstrate that NE-induced mucin production requires reactive oxygen species (ROS) production, which activates TACE, resulting in TGF-α shedding, and EGFR phosphorylation in NCI-H292 epithelial cells.

中文翻译：

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ROS / TACE在中性粒细胞弹性蛋白酶诱导的NCI-H292气道上皮细胞黏液分泌过多中的作用。

慢性阻塞性肺疾病（COPD）会引起并发症，尤其是在病情加重期间，黏液产生过多，导致气道阻塞和细菌感染。在气道分泌物中高水平检测到中性粒细胞弹性蛋白酶（NE），它是粘蛋白产生的主要诱导剂。了解NE诱导的粘蛋白过量生产的机制可能会导致COPD的新疗法。已知表皮生长因子受体（EGFR）的激活及其下游信号传导级联参与粘蛋白的产生。但是，NE诱导EGFR激活的机制仍不清楚。肿瘤坏死因子-α转化酶（TACE）在气道上皮细胞中裂解促转化生长因子（TGF）-α，释放出成熟的可溶性TGF-α形式，该形式随后结合并激活EGFR。