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

Makoto Yanagisawa, Kinichi Nakashima, Hirokazu Arakawa, Kazuhiro Ikenaka, Kanji Yoshida, Tadamitsu Kishimoto, Tatsuhiro Hisatsune, Tetsuya Taga

Research output: Contribution to journalArticle

43 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1498-1504
Number of pages7
JournalJournal of Neurochemistry
Volume74
Issue number4
DOIs
Publication statusPublished - Apr 3 2000
Externally publishedYes

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Cytokine Receptor gp130
Neuroepithelial Cells
Interleukin-11
STAT3 Transcription Factor
Astrocytes
Transcription Factors
Chemical activation
Cells
Cytokines
Interleukin-6
Signal transduction
Phosphorylation
Glial Fibrillary Acidic Protein
Membrane Glycoproteins
Genetic Promoter Regions
Transcriptional Activation
Transfection
Tyrosine
Signal Transduction
Brain

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Astrocyte differentiation of fetal neuroepithelial cells by interleukin- 11 via activation of a common cytokine signal transducer, gp130, and a transcription factor, STAT3. / Yanagisawa, Makoto; Nakashima, Kinichi; Arakawa, Hirokazu; Ikenaka, Kazuhiro; Yoshida, Kanji; Kishimoto, Tadamitsu; Hisatsune, Tatsuhiro; Taga, Tetsuya.

In: Journal of Neurochemistry, Vol. 74, No. 4, 03.04.2000, p. 1498-1504.

Research output: Contribution to journalArticle

Yanagisawa, Makoto ; Nakashima, Kinichi ; Arakawa, Hirokazu ; Ikenaka, Kazuhiro ; Yoshida, Kanji ; Kishimoto, Tadamitsu ; Hisatsune, Tatsuhiro ; Taga, Tetsuya. / Astrocyte differentiation of fetal neuroepithelial cells by interleukin- 11 via activation of a common cytokine signal transducer, gp130, and a transcription factor, STAT3. In: Journal of Neurochemistry. 2000 ; Vol. 74, No. 4. pp. 1498-1504.
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