Open Access

ARTICLE

Roles of ROS/TACE in neutrophil elastase-induced mucus hypersecretion in NCI-H292 airway epithelial cells

Li Qi, Zhou Xiangdong, Yu Hongmei, Nie Xiaohong, Xu Xiaoyan

Department of Respiratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China

* Corresponding Author: Zhou XD,

European Cytokine Network 2010, 21(3), 177-185. https://doi.org/10.1684/ecn.2010.0195

Accepted 31 May 2010;

Abstract

Complications arise in chronic obstructive pulmonary diseases (COPD) with excessive mucus pro-duction, 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 signal-ing 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 oxy-gen species (ROS) production, which activates TACE, resulting in TGF-α shedding, and EGFR phosphorylation in NCI-H292 epithelial cells.

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