Members of the C/EBP transcription factor family stimulate expression of the human and rat surfactant protein A (SP-A) genes.
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/EBP delta 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 microM 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.
Rosenberg
Elizabeth
E
Institute for Environmental Medicine, University of Pennsylvania School of Medicine, Room 1, John Morgan Building, Philadelphia, PA 19104-6068, USA.
Li
Feng
F
Reisher
Samuel R
SR
Wang
Mengshu
M
Gonzales
Linda W
LW
Ewing
Jacqueline R
JR
Malek
Syeda
S
Ballard
Philip L
PL
Notarfrancesco
Kathleen
K
Shuman
Henry
H
Feinstein
Sheldon I
SI
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D008168:Lung / Q000502:physiology; D011510:Proteolipids / Q000096:biosynthesis / Q000235:genetics*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000096:biosynthesis / Q000235:genetics*; D051381:Rats; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D022762:CCAAT-Enhancer-Binding Proteins; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D014157:Transcription Factors