CYP2B1 is regulated by C/EBPα and C/EBPδ in lung epithelial cells

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/EBPα and C/EBPδ in pulmonary epithelial CYP2B1 gene expression. A 1.3 kb CYP2B1 promoter fragment which recently has been shown to confer lung tissue- and cell- specific expression of CYP2B1 in transgenic mice was used in transient transfection studies. Both C/EBPα and C/EBPδ transactivated the CYP2B1 promoter in the lung epithelial cell lines A549 and NCI-H441. C/EBPα 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/EBPα and C/EBPδ. 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. (C) 2000 Academic Press.