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Astrocyte Differentiation of Fetal Neuroepithelial Cells by Interleukin‐11 via Activation of a Common Cytokine Signal Transducer, gp130, and a Transcription Factor, STAT3
Author(s) -
Yanagisawa Makoto,
Nakashima Kinichi,
Arakawa Hirokazu,
Ikenaka Kazuhiro,
Yoshida Kanji,
Kishimoto Tadamitsu,
Hisatsune Tatsuhiro,
Taga Tetsuya
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0741498.x
Subject(s) - glycoprotein 130 , neuroepithelial cell , biology , astrocyte , microbiology and biotechnology , stat3 , tyrosine phosphorylation , signal transduction , neural stem cell , endocrinology , stem cell , central nervous system
The interleukin (IL)‐6 family cytokines utilize membraneglycoprotein gp130 in common as a critical signal‐transducing receptorcomponent. IL‐11, a cytokine initially identified as a plasmacytoma growthfactor, belongs to this family. We show here that IL‐11 and its cognatereceptor components are expressed in fetal mouse neuroepithelial cells. Wealso show that after 4 days of culture with IL‐11, cells with typicalastrocytic morphologies expressing glial fibrillary acidic protein (GFAP; amarker for astrocytes) come out. This differentiation process is totallydependent on the gp130‐mediated signal‐transduction pathway involvingactivation of a latent cytoplasmic transcription factor, STAT3 (for s ignal t ransducer and a ctivator of t ranscription 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.