Roles of ROS/TACE in neutrophil elastase-induced mucus hypersecretion in NCI-H292 airway epithelial cells.
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.
Qi
Li
L
Department of Respiratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Xiangdong
Zhou
Z
Hongmei
Yu
Y
Xiaohong
Nie
N
Xiaoyan
Xu
X
D051722:ADAM Proteins / Q000378:metabolism*; D000072198:ADAM17 Protein; D001483:Base Sequence; D001980:Bronchi / Q000201:enzymology / Q000378:metabolism*; D045744:Cell Line, Tumor; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism*; D055271:Mucin 5AC / Q000096:biosynthesis / Q000378:metabolism; D009093:Mucus / Q000201:enzymology / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000201:enzymology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D017382:Reactive Oxygen Species; D066246:ErbB Receptors; D019272:Leukocyte Elastase; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human