title: Members of the C/EBP transcription factor family stimulate expression of the human and rat surfactant protein A (SP-A) genes.
abstract: 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.
authors.affiliation: Institute for Environmental Medicine, University of Pennsylvania School of Medicine, Room 1, John Morgan Building, Philadelphia, PA 19104-6068, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Rosenberg
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Samuel R
authors.initials: SR
authors.lastname: Reisher
authors.forename: Mengshu
authors.initials: M
authors.lastname: Wang
authors.forename: Linda W
authors.initials: LW
authors.lastname: Gonzales
authors.forename: Jacqueline R
authors.initials: JR
authors.lastname: Ewing
authors.forename: Syeda
authors.initials: S
authors.lastname: Malek
authors.forename: Philip L
authors.initials: PL
authors.lastname: Ballard
authors.forename: Kathleen
authors.initials: K
authors.lastname: Notarfrancesco
authors.forename: Henry
authors.initials: H
authors.lastname: Shuman
authors.forename: Sheldon I
authors.initials: SI
authors.lastname: Feinstein
mesh_terms: 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
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D014157:Transcription Factors