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Published ahead of print on June 6, 2008, doi:10.1165/rcmb.2007-0262OC

Am. J. Respir. Cell Mol. Biol., Volume 39, Number 5, November 2008, 598-609

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Submitted on July 11, 2007
Revised on May 28, 2008

The Role of Nox4 in Oxidative Stress-Induced MUC5AC Overexpression in Human Airway Epithelial Cells

Hyun Jik Kim1, Young-Duck Park2, Uk Yeol Moon3, Jun-Hee Kim4, Ju Hyun Jeon2, Jeung-Gweon Lee2, Yun Soo Bae5, and Joo-Heon Yoon6*

1 Department of Otolaryngology - Head and Neck Surgery, Chung-Ang University College of Medicine, Seoul, Korea, Republic of; Department of Medicine, Yonsei University College of Medicine, The Graduate School, Seoul, Korea, Republic of, 2 Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea, Republic of, 3 Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea, Republic of; Department of Medicine, Yonsei University College of Medicine, The Graduate School, Seoul, Korea, Republic of, 4 Department of Otolaryngology - Head and Neck Surgery, Chung-Ang University College of Medicine, Seoul, Korea, Republic of, 5 The Center for Cell Signaling Research, Division of Molecular Life Sciences, and Department of Biological Science, Ewha Womans University, Seoul, Korea, Republic of, 6 Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea, Republic of; Yonsei University College of Medicine, The Airway Mucus Institute, Seoul, Korea, Republic of; Yonsei University College of Medicine, BK 21 Project for Medical Science, Seoul, Korea, Republic of

* To whom correspondence should be addressed. E-mail: jhyoon{at}yumc.yonsei.ac.kr.

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 (H2O2) and the mechanism by which these genes are upregulated in normal human nasal epithelial (NHNE) cells. Exogenous H2O2 induced the ligand independent activation of epidermal growth factor receptors (EGFR) and the subsequent activation of ERK1 MAP kinase, resulting in the induction of intracellular ROS generation. Through this signal pathway, exogenous H2O2 markedly induced overexpression of the MUC5AC gene alone. In addition, Nox4, a subtype of non phagocytic NADPH oxidase, was found to play a key role in intracellular ROS generation and exogenous H2O2 induced MUC5AC gene expression in NHNE cells.




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