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Published ahead of print on August 7, 2008
Am. J. Respir. Cell Mol. Biol. 2008, doi:10.1165/rcmb.2007-0377OC
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Submitted on October 18, 2007
Revised on August 7, 2008

Signal Pathway of 17b-estradiol-induced MUC5B Expression in Human Airway Epithelial Cells

Hye Joung Choi1, Yoo-Sam Chung2, Hyun Jik Kim3, Uk Yeol Moon4, Yeon Ho Choi4, Isabelle Van Seuningen5, Seung Joon Baek6, Ho-Geun Yoon7, and Joo-Heon Yoon8*

1 Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea, Republic of, 2 Department of Otolaryngology, University of Ulsan, Asan Medical Center, College of Medicine, Seoul, Korea, Republic of, 3 Department of Otolaryngology - Head and Neck Surgery, Chung-Ang University College of Medicine, Seoul, Korea, Republic of, 4 Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea, Republic of; BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea, Republic of, 5 The Unite INSERM 560, Place de Verdun, Lille Cedex, France, 6 Department of Pathobiology, University of Tennessee, College of Veterinary Medicine, Knoxville, Tennessee, USA, 7 Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Korea, Republic of, 8 Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea, Republic of; The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Korea, Republic of; BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea, Republic of

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

MUC5B is a major mucin of the human respiratory tract, and it is not clear how MUC5B expression is regulated in various airway diseases. The goal of this study was to determine the mechanisms by which 17{beta}-estradiol induces MUC5B gene expression in airway epithelial cells. It was found that E2, a sex hormone, stimulate MUC5B gene overexpression by interaction with estrogen receptor {alpha} (ER {alpha}) and by acting through extracellular signal-regulated kinase 1/2 (ERK1/2)-MAP kinase (MAPK). Pre-treatment with ER antagonist ICI 182,780 blocked both E2-induced ERK1/2-MAPK activation and MUC5B gene expression. It was also found that the activation of p90 ribosomal S 6 protein kinase 1 (RSK1), cAMP-response element-binding protein (CREB) and cAMP-response element (CRE) (-956 region of the MUC5B promoter) responsive signaling cascades via ERK1/2 MAPK are crucial aspects of the intracellular mechanisms that mediate MUC5B gene expression. Taken together, these studies give additional insights into the molecular mechanism of hormone-induced MUC5B gene expression and enhance our understanding of abnormal mucin secretion in response to hormonal imbalances.






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