Glucocorticoids regulate the CCSP and CYP2B1 promoters via C/EBPbeta and delta in lung cells

Biochem Biophys Res Commun. 2002 May 10;293(3):907-12. doi: 10.1016/S0006-291X(02)00319-4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CCAAT-Enhancer-Binding Protein-beta / physiology
  • CCAAT-Enhancer-Binding Protein-delta
  • CCAAT-Enhancer-Binding Proteins / physiology*
  • Cell Line
  • Cells, Cultured
  • Cytochrome P-450 CYP2B1 / genetics*
  • Dexamethasone / pharmacology*
  • Glucocorticoids / pharmacology*
  • Lung / cytology
  • Lung / metabolism*
  • Promoter Regions, Genetic
  • Protein Biosynthesis
  • Proteins / genetics*
  • RNA, Messenger / biosynthesis
  • Rats
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / metabolism
  • Transcription Factors*
  • Transcriptional Activation
  • Uteroglobin*

Substances

  • CCAAT-Enhancer-Binding Protein-beta
  • CCAAT-Enhancer-Binding Proteins
  • Cebpd protein, rat
  • Glucocorticoids
  • Proteins
  • RNA, Messenger
  • Scgb1a1 protein, rat
  • Transcription Factors
  • CCAAT-Enhancer-Binding Protein-delta
  • Dexamethasone
  • Uteroglobin
  • Cytochrome P-450 CYP2B1