Astrocyte differentiation of fetal neuroepithelial cells by interleukin-11 via activation of a common cytokine signal transducer, gp130, and a transcription factor, STAT3.
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.
Yanagisawa
M
M
Department of Molecular Cell Biology, Tokyo Medical and Dental University, Japan.
Nakashima
K
K
Arakawa
H
H
Ikenaka
K
K
Yoshida
K
K
Kishimoto
T
T
Hisatsune
T
T
Taga
T
T
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology*; D005260:Female; D005333:Fetus / Q000166:cytology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D017370:Interleukin-11 / Q000096:biosynthesis / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000502:physiology; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013687:Telencephalon / Q000166:cytology / Q000196:embryology; D015534:Trans-Activators / Q000378:metabolism*
D015703:Antigens, CD; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; C494200:Il6st protein, mouse; D017370:Interleukin-11; D008562:Membrane Glycoproteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D050822:Cytokine Receptor gp130