CYP2B1 Is Regulated by C/EBP#alpha# and C/EBP#delta# in Lung Epithelial Cells

摘要

Pulmonary expression of several cytochrome P450 (CYP) monooxygenases is detected late in gestation.Little is known of the factors involved in this differentiation-dependent expression.C/EBP factors are known regulators of differentiation and differentiation-dependent gene expression in several tissues.In this study we demonstrate the importance of C/EBP#alpha# and C/EBP#delta# in pulmonary epithelial CYP2B1 gene exprsession.A 1.3 kb CYP2B1 promoter fragment which recently has been shown to confer lung tissur- and cell-specific sexpression of CYP2B1 in transgenic mice was used in transient transfection studies.Both C/EBP#alpha# and C/EBP#delta# transactivated the CYP2B1 promoter int eh lung epithelial cell lines A549 and NCI-H441.C/EBP#alpha# in nuclear extracts from isolated rat primary bronchiolar Clara cells was capable of interacting with a C/EBP-binding site in the proximal CYP2B1 promoter.Site-directed mutagenesis studies showed that this proximal C/EBP-binding site is necessary for transactivation of the CYP2B1 gene by C/EBP#alpha# and C/EBP#alpha#.This study shows that C/EBP factors have a role in pulmonary CYP2B1 expression and suggests that these transcription factors may be important for the differentiation-dependent expression of CYP2B1 in the lung.