Activation of c-Myb transcription factor is critical for PMA-induced lysozyme expression in airway epithelial cells.
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.
Moon
Uk Yeol
UY
The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Korea.
Bae
Jung Ho
JH
Kim
Chang-Hoon
CH
Kim
Hyun Jik
HJ
Kang
Ju Wan
JW
Yoon
Joo-Heon
JH
D000890:Anti-Infective Agents; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D009113:Muramidase / Q000187:drug effects / Q000235:genetics*; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism*; D012137:Respiratory System / Q000166:cytology*; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014157:Transcription Factors
D000890:Anti-Infective Agents; D020598:Proto-Oncogene Proteins c-myb; D014157:Transcription Factors; D048049:Extracellular Signal-Regulated MAP Kinases; D009113:Muramidase; D013755:Tetradecanoylphorbol Acetate