Activation of c-Myb transcription factor is critical for PMA-induced lysozyme expression in airway epithelial cells

Uk Yeol Moon, Jung Ho Bae, Chang Hoon Kim, Hyun Jik Kim, Ju Wan Kang, Joo Heon Yoon

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)476-487
Number of pages12
JournalJournal of Cellular Biochemistry
Volume111
Issue number2
DOIs
Publication statusPublished - 2010 Oct 1

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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