Abbreviations used: BMP, bone morphogenetic protein; CNTF, ciliary neurotrophic factor; E, embryonic day; GFAP, glial fibrillary acidic protein; IL, interleukin; LIF, leukemia inhibitory factor; LIFR, LIF receptor; MAP2, microtubule-associated protein 2; MAPK, mitogen-activated protein kinase; MAPKK, MAPK kinase; OSM, oncostatin M; OSMR, OSM receptor; sIL-6R, soluble IL-6 receptor; STAT3, signal transducer and activator of transcription 3.
Astrocyte Differentiation of Fetal Neuroepithelial Cells by Interleukin-11 via Activation of a Common Cytokine Signal Transducer, gp130, and a Transcription Factor, STAT3
Article first published online: 18 JAN 2002
Journal of Neurochemistry
Volume 74, Issue 4, pages 1498–1504, April 2000
How to Cite
Yanagisawa, M., Nakashima, K., Arakawa, H., Ikenaka, K., Yoshida, K., Kishimoto, T., Hisatsune, T. and Taga, T. (2000), Astrocyte Differentiation of Fetal Neuroepithelial Cells by Interleukin-11 via Activation of a Common Cytokine Signal Transducer, gp130, and a Transcription Factor, STAT3. Journal of Neurochemistry, 74: 1498–1504. doi: 10.1046/j.1471-4159.2000.0741498.x
- Issue published online: 18 JAN 2002
- Article first published online: 18 JAN 2002
- Astrocyte differentiation;
- Neuroepithelial cells;
- Interleukin-6 family of cytokines
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.