CCAAT/enhancer-binding protein activates the CD14 promoter and mediates transforming growth factor beta signaling in monocyte development

J Biol Chem. 1999 Aug 13;274(33):23242-8. doi: 10.1074/jbc.274.33.23242.


Transcription factors from the CCAAT/enhancer-binding protein (C/EBP) family play important roles in myeloid cell differentiation. CD14 is a monocyte/macrophage differentiation marker and is strongly up-regulated during monocytic cell differentiation. Here, we report the direct binding of C/EBP to the monocyte-specific promoter of CD14. Transactivation analyses demonstrate that C/EBP family members significantly activate the CD14 promoter. These data indicate that C/EBP is directly involved in the regulation of CD14 gene expression. When myelomonoblastic U937 cells are treated with vitamin D(3) and TGF-beta, they differentiate toward monocytic cells. Using specific antibodies against different C/EBP family members in electrophoretic mobility shift assays and Western blot assays, we have identified a specific increase in the DNA binding and the expression of C/EBPalpha and C/EBPbeta during U937 monocytic cell differentiation, and we found C/EBPalpha and C/EBPbeta bind to the promoter in heterodimer. Furthermore, with stably transfected cell lines, we demonstrate that the C/EBP binding site in the CD14 promoter plays a critical role for mediating TGF-beta signaling in the synergistic activation of CD14 expression by vitamin D(3) and TGF-beta during U937 differentiation. This may indicate that C/EBPs have important functions in the process of TGF-beta signal transduction during monocyte differentiation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • CCAAT-Enhancer-Binding Proteins
  • Cell Differentiation
  • Cholecalciferol / metabolism
  • DNA Primers
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Lipopolysaccharide Receptors / genetics*
  • Monocytes / cytology
  • Monocytes / metabolism*
  • Nuclear Proteins / metabolism*
  • Promoter Regions, Genetic*
  • Protein Binding
  • Signal Transduction*
  • Transcriptional Activation
  • Transforming Growth Factor beta / metabolism*
  • U937 Cells


  • CCAAT-Enhancer-Binding Proteins
  • DNA Primers
  • DNA-Binding Proteins
  • Lipopolysaccharide Receptors
  • Nuclear Proteins
  • Transforming Growth Factor beta
  • Cholecalciferol