Crosstalk between platelet-derived growth factor-induced Nox4 activation and MUC8 gene overexpression in human airway epithelial cells.
Reactive oxygen species (ROS) contribute to chronic airway inflammation, and NADPH oxidase (Nox) is an important source of ROS. However, little is known of the role that ROS play in chronic upper respiratory tract inflammation. We investigated the mechanism of ROS generation and its association with mucin gene overexpression in the nasal epithelium. The level of platelet-derived growth factor (PDGF) expression was increased in sinusitis mucosa, and high-level PDGF expression induced intracellular ROS, followed by MUC8 gene overexpression in normal human nasal epithelial cells. Knockdown of Nox4 expression with Nox4 siRNA decreased PDGF-induced intracellular ROS and MUC8 expression. Infection with an adenovirus containing Nox4 cDNA resulted in Nox4 overexpression and increased intracellular levels of ROS and MUC8 expression. PDGF and Nox4 overexpression are essential components of intracellular ROS generation and may contribute to chronic inflammation in the nasal epithelium through induction of MUC8 overexpression.
Department of Otolaryngology-Head and Neck Surgery, Chung-Ang University College of Medicine, Seoul, Korea.
Hyun Jik
HJ
Kim
Chang-Hoon
CH
Kim
Ji-Hwan
JH
Ryu
Jung Hee
JH
Joo
Sang-Nam
SN
Lee
Min-Ji
MJ
Kim
Jeung-Gweon
JG
Lee
Yun Soo
YS
Bae
Joo-Heon
JH
Yoon
D000256:Adenoviridae; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002908:Chronic Disease; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000201:enzymology / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D009077:Mucins / Q000235:genetics / Q000378:metabolism*; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D009297:Nasal Mucosa / Q000378:metabolism / Q000503:physiopathology; D018384:Oxidative Stress; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D012852:Sinusitis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; C105059:MUC8 protein, human; D009077:Mucins; D010982:Platelet-Derived Growth Factor; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human