Astrocyte differentiation of fetal neuroepithelial cells by interleukin-11 via activation of a common cytokine signal transducer, gp130, and a transcription factor, STAT3

J Neurochem. 2000 Apr;74(4):1498-504. doi: 10.1046/j.1471-4159.2000.0741498.x.

Abstract

The interleukin (IL)-6 family cytokines utilize membrane glycoprotein gp130 in common as a critical signal-transducing receptor component. IL-11, a cytokine initially identified as a plasmacytoma growth factor, belongs to this family. We show here that IL-11 and its cognate receptor components are expressed in fetal mouse neuroepithelial cells. We also show that after 4 days of culture with IL-11, cells with typical astrocytic morphologies expressing glial fibrillary acidic protein (GFAP; a marker for astrocytes) come out. This differentiation process is totally dependent on the gp130-mediated signal-transduction pathway involving activation of a latent cytoplasmic transcription factor, STAT3 (for signal transducer and activator of transcription 3), because (a) IL-11-induced astrocyte differentiation is not observed when neuroepithelial cells prepared from gp130-deficient mice were used, (b) stimulation of neuroepithelial cells by IL-11 rapidly induces tyrosine-phosphorylation of STAT3, and (c) transfection of neuroepithelial cells with a dominant-negative form of STAT3 inhibits IL-11-induced activation of the GFAP gene promoter. We have further identified, in the GFAP promoter region, a STAT3 site at which nucleotide substitutions almost completely abolished the IL-11-induced GFAP promoter activation. Taken together, it is suggested that IL-11 contributes to astrocytogenesis in fetal brain via activation of gp130 and STAT3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism*
  • Astrocytes / cytology*
  • Astrocytes / metabolism
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Cytokine Receptor gp130
  • DNA-Binding Proteins / metabolism*
  • Epithelial Cells / cytology*
  • Female
  • Fetus / cytology
  • Gene Expression Regulation, Developmental / drug effects
  • Glial Fibrillary Acidic Protein / genetics
  • Interleukin-11 / biosynthesis
  • Interleukin-11 / pharmacology*
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred ICR
  • Pregnancy
  • Promoter Regions, Genetic / drug effects
  • Promoter Regions, Genetic / physiology
  • STAT3 Transcription Factor
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Telencephalon / cytology
  • Telencephalon / embryology
  • Trans-Activators / metabolism*

Substances

  • Antigens, CD
  • DNA-Binding Proteins
  • Glial Fibrillary Acidic Protein
  • Il6st protein, mouse
  • Interleukin-11
  • Membrane Glycoproteins
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Trans-Activators
  • Cytokine Receptor gp130