Members of the C/EBP transcription factor family stimulate expression of the human and rat surfactant protein A (SP-A) genes

• Published in: Biochimica et biophysica acta 2002-05, Vol.1575 (1), p.82-90
• Main Authors: Rosenberg, Elizabeth, Li, Feng, Reisher, Samuel R., Wang, Mengshu, Gonzales, Linda W., Ewing, Jacqueline R., Malek, Syeda, Ballard, Philip L., Notarfrancesco, Kathleen, Shuman, Henry, Feinstein, Sheldon I.
• Format: Article
• Language: English
• Subjects: Animals; CCAAT-Enhancer-Binding Proteins - genetics; CCAAT-Enhancer-Binding Proteins - metabolism; Cells, Cultured; Decoy oligonucleotide; Gene Expression Regulation; Gene regulation; Gene Silencing; Humans; Lung - physiology; NCI-H441 cell; Proteolipids - biosynthesis; Proteolipids - genetics; Pulmonary surfactant; Pulmonary Surfactant-Associated Protein A; Pulmonary Surfactant-Associated Proteins; Pulmonary Surfactants - biosynthesis; Pulmonary Surfactants - genetics; Rats; Transcription Factors - genetics; Transcription Factors - metabolism; Transcriptional silencer; Type II cell
• ISSN: 0167-4781; 0006-3002; 1879-2634
• DOI: 10.1016/S0167-4781(02)00287-7

Members of the CCAAT enhancer binding protein (C/EBP) transcription factor family were detected in fetal lung of both human and rat. In rat lung, the level of C/EBPs increased with time of gestation, peaking around birth. In adult rat lung, C/EBPs were localized to the alveolar type II cells. The effect of C/EBPs on pulmonary surfactant protein A (SP-A), which is also expressed late in gestation, was investigated. In contrast to control plasmids, C/EBPδ expressing plasmids reversed the action of a transcriptional silencer just upstream of the rat SP-A promoter. In order to test the effect of C/EBPs on endogenous SP-A gene expression, cells that express SP-A were exposed to a phosphorothioate-substituted, double-stranded oligonucleotide matching the consensus C/EBP binding site (decoy oligonucleotide) at concentrations from 0.5 to 10 μM for 72 h. A mutant oligonucleotide with an 8-base pair (bp) substitution served as a control. The decoy oligonucleotide reduced SP-A mRNA as much as 75% compared to a mutant oligonucleotide both in the human lung cell line, NCI-H441, and in primary human fetal alveolar type II cells. The data indicate that C/EBPs facilitate SP-A gene expression, possibly by overcoming transcriptional silencing.