@Article{ecn.2010.0195,
AUTHOR = {Li Qi, Zhou Xiangdong, Yu Hongmei, Nie Xiaohong, Xu Xiaoyan},
TITLE = {Roles of ROS/TACE in neutrophil elastase-induced mucus hypersecretion in NCI-H292 airway epithelial cells},
JOURNAL = {European Cytokine Network},
VOLUME = {21},
YEAR = {2010},
NUMBER = {3},
PAGES = {177--185},
URL = {http://www.techscience.com/ECN/v21n3/65855},
ISSN = {1952-4005},
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.},
DOI = {10.1684/ecn.2010.0195}
}