The role of Nox4 in oxidative stress-induced MUC5AC overexpression in human airway epithelial cells.
Mucus hypersecretion is a prominent manifestation in patients with chronic inflammatory airway diseases, and MUC5AC is a major airway mucin. It is well known that reactive oxygen species (ROS) may be involved in the pathogenesis of various inflammatory airway diseases. The purpose of this study was to identify which secreted mucin genes are induced by exogenous hydrogen peroxide and the mechanism by which these genes are up-regulated in normal human nasal epithelial (NHNE) cells. Exogenous H(2)O(2) induced the ligand-independent activation of epidermal growth factor receptors (EGFR) and the subsequent activation of ERK1 mitogen-activated protein kinase, resulting in the induction of intracellular ROS generation. Through this signal pathway, exogenous H(2)O(2) markedly induced overexpression of the MUC5AC gene alone. In addition, Nox4, a subtype of nonphagocytic NADPH oxidase, was found to play a key role in intracellular ROS generation and exogenous H(2)O(2)-induced MUC5AC gene expression in NHNE cells.
Kim
Hyun Jik
HJ
Department of Otolaryngology, Head and Neck Surgery, Chung-Ang University College of Medicine, Seoul, Korea.
Park
Young-Duck
YD
Moon
Uk Yeol
UY
Kim
Jun-Hee
JH
Jeon
Ju Hyun
JH
Lee
Jeung-Gweon
JG
Bae
Yun Soo
YS
Yoon
Joo-Heon
JH
D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D020397:Goblet Cells / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008024:Ligands; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D055271:Mucin 5AC; D009077:Mucins / Q000235:genetics / Q000378:metabolism*; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D009297:Nasal Mucosa / Q000378:metabolism*; D009666:Nose / Q000187:drug effects; D018384:Oxidative Stress; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism
D008024:Ligands; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human; D066246:ErbB Receptors; D048052:Mitogen-Activated Protein Kinase 3