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 - 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

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