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J. Biol. Chem., Vol. 280, Issue 8, 6676-6681, February 25, 2005

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Prostaglandin E₂ Induces MUC8 Gene Expression via a Mechanism Involving ERK MAPK/RSK1/cAMP Response Element Binding Protein Activation in Human Airway Epithelial Cells^*

Kyou-Nam Cho, Jae Young Choi¶, Chang-Hoon Kim¶, Seung Joon Baek||, Kwang Chul Chung**, Uk Yeol Moon, Kyung-Su Kim¶, Won-Jae Lee, Ja Seok Koo, and Joo-Heon Yoon¶¶¶

From the ^¶Department of Otorhinolaryngology, the The Airway Mucus Institute, the BK21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul 120-752, South Korea, the ^||Department of Pathobiology, University of Tennessee, College of Veterinary Medicine, Knoxville, Tennessee 37996-4542, the Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030-4009, the ^**Department of Biology, College of Science, Yonsei University, Seoul 120-749, South Korea, and the Division of Molecular Life Science, Ewha Women's University, Seoul 120-750, South Korea

MUC8 gene expression is overexpressed in nasal polyp epithelium and is also increased by treatment with inflammatory mediators in nasal epithelial cells. These data suggest that MUC8 may be one of important mucin genes expressed in human airway. However, the mechanisms of various inflammatory mediator-induced MUC8 gene expression in normal nasal epithelial cells remain unclear. We examined the mechanism by which prostaglandin E₂ (PGE2), an arachidonic acid metabolite, increases MUC8 gene expression levels. Here, we show that ERK mitogen-activated protein kinase is essential for PGE2-induced MUC8 gene expression in normal human nasal epithelial cells and that p90 ribosomal S 6 protein kinase 1 (RSK1) mediates the PGE2-induced phosphorylation of cAMP-response element binding protein. Our results also indicate that cAMP-response element at the –803 region of the MUC8 promoter is an important site of PGE2-induced MUC8 gene expression. In conclusion, this study gives insights into the molecular mechanism of PGE2-induced MUC8 gene expression in human airway epithelial cells.

Received for publication, November 10, 2004 , and in revised form, December 16, 2004.

^* This work was supported by Korean Research Foundation Grant KRF-2004-015-E00074. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶¶ To whom correspondence should be addressed: Dept. of Otorhinolaryngology, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Korea. Tel.: 82-2-361-8484; Fax: 82-2-393-0580; E-mail: jhyoon{at}yumc.yonsei.ac.kr.

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