VEGF-A-induced immature DCs not mature DCs differentiation into endothelial-like cells through ERK1/2-dependent pathway

Cell Biochem Funct. 2011 Jun;29(4):294-302. doi: 10.1002/cbf.1752. Epub 2011 Apr 25.

Abstract

Dendritic cells (DCs) are professional antigen-presenting cells that play an important role in anti-tumour immunity. Endothelial-like differentiation of DCs is an interesting phenomenon. The specific role of vascular endothelial growth factor-A (VEGF-A) on the differentiation of immature DCs (iDCs) and mature DCs (mDCs) is worth further research. Here, we show that VEGF-A can induce iDCs to differentiate into endothelial-like cells (ELCs). But it has no obvious influence on mDCs. In the process of endothelial-like differentiation of iDCs, a sustained activation of extracellular signal-regulated kinase (ERK1/2) and cAMP response element binding protein (CREB) was detected. VEGF-A induced the activation of ERK1/2, and led to the nuclear translocation of phosphorylation ERK1/2. Incubation of iDCs with the ERK1/2 upstream kinase MEK1/2 inhibitor PD98059, blocked the phosphorylation of ERK1/2 and CREB as well as the endothelial-like differentiation of iDCs. These data suggest that VEGF-A induces endothelial-like differentiation of iDCs not mDCs through ERK1/2 signalling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Cell Differentiation*
  • Cells, Cultured
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / physiology*
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Flavonoids / pharmacology
  • Flow Cytometry
  • Humans
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Phosphorylation
  • Signal Transduction
  • Umbilical Veins / cytology
  • Vascular Endothelial Growth Factor A / pharmacology*

Substances

  • Cyclic AMP Response Element-Binding Protein
  • Flavonoids
  • Vascular Endothelial Growth Factor A
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one