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Activation of c‐Myb transcription factor is critical for PMA‐induced lysozyme expression in airway epithelial cells
Author(s) -
Moon Uk Yeol,
Bae Jung Ho,
Kim ChangHoon,
Kim Hyun Jik,
Kang Ju Wan,
Yoon JooHeon
Publication year - 2010
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22730
Subject(s) - lysozyme , myb , protein kinase c , transcription factor , biology , microbiology and biotechnology , phorbol , signal transduction , gene expression , transcription (linguistics) , gene , biochemistry , linguistics , philosophy
Lysozyme is a major component of airway epithelial secretions, acts as cationic anti‐microbial protein for innate immunity. Although lysozyme plays an important role in airway defense and is a key component of airway secretions under inflammatory conditions, little is understood about the regulation of its expression and the associated signaling pathway. We wanted to examine whether Phorbol 12‐myristate 13‐acetate (PMA), one of PKC activators, treatment of the airway epithelial cell line NCI‐H292 increases lysozyme gene expression. In this study, we sought to determine which signal molecules are involved in PMA‐induced lysozyme gene expression. We found that PKC and mitogen‐activating protein/ERK2 kinase are essential for PMA‐induced lysozyme expression and also mediate the PMA‐induced activation of c‐Myb protein. We identified a proximal region of the lysozyme promoter essential for promoter activity containing c‐Myb transcription factor binding site. Additionally, by site‐directed promoter mutagenesis, we identified that c‐Myb preferred the CAA motif of the −85/−73 region of the lysozyme promoter. Finally, we showed that overexpression of c‐Myb without PMA treatment increased the lysozyme promoter activity and protein expression. From these results, we conclude that PMA induces overexpression of lysozyme via ERK1/2 MAP kinase—c‐Myb signaling pathways in NCI‐H292 cells. J. Cell. Biochem. 111: 476–487, 2010. © 2010 Wiley‐Liss, Inc.