title: Glucocorticoids regulate the CCSP and CYP2B1 promoters via C/EBPbeta and delta in lung cells.
abstract: Glucocorticoids have several important roles in the lung and play a key role in lung development and maturation. However, the specific molecular mechanisms of glucocorticoid action in lung are unclear. In this study, we have investigated two glucocorticoid-regulated genes expressed in the lung epithelium, the secretory protein CCSP, and the P450-enzyme CYP2B1. In transient transfections of lung epithelial cells, glucocorticoids increased expression from the CCSP and CYP2B1 promoters and we demonstrated that induction was dependent on the integrity of C/EBP-binding sites in both promoters. Electrophoretic mobility shift assays revealed increased DNA-binding of C/EBPbeta and C/EBPdelta after glucocorticoid treatment, which was not correlated to altered protein levels. The results of this study indicate a previously unknown role for C/EBP transcription factors in glucocorticoid signaling in the lung epithelium.
authors.affiliation: Department of Medical Nutrition, Karolinska Institute, NOVUM, Huddinge University Hospital, SE-141 86 Huddinge, Sweden.
authors.forename: Tove
authors.initials: T
authors.lastname: Berg
authors.forename: Tobias N
authors.initials: TN
authors.lastname: Cassel
authors.forename: Per E
authors.initials: PE
authors.lastname: Schwarze
authors.forename: Magnus
authors.initials: M
authors.lastname: Nord
mesh_terms: D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000502:physiology; D051743:CCAAT-Enhancer-Binding Protein-delta; D022762:CCAAT-Enhancer-Binding Proteins / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D019362:Cytochrome P-450 CYP2B1 / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors; D015533:Transcriptional Activation; D014598:Uteroglobin
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; C497254:Cebpd protein, rat; D005938:Glucocorticoids; D011506:Proteins; D012333:RNA, Messenger; C556391:Scgb1a1 protein, rat; D014157:Transcription Factors; D051743:CCAAT-Enhancer-Binding Protein-delta; D003907:Dexamethasone; D014598:Uteroglobin; D019362:Cytochrome P-450 CYP2B1