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Mol Biol Cell. 2009 Jan;20(1):188-99. doi: 10.1091/mbc.E08-05-0463. Epub 2008 Oct 29.

Interleukin-6 and neural stem cells: more than gliogenesis.

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Department of Molecular and Cell Biology, School of Biological Sciences, College of Science, Nanyang Technological University, Singapore, Singapore.


Besides its wide range of action as a proinflammatory cytokine in the immune system, interleukin-6 (IL-6) has also attracted much attention due to its influence on the nervous system. In the present study we show that the designer fusion protein H-IL-6, consisting of IL-6 and its specific receptor IL-6R-alpha, but not IL-6 alone, mediates both neuro- as well as gliogenesis. Using immunocytochemistry, Western blot, and patch-clamp recording, we demonstrate that H-IL-6 induces the differentiation of neural stem cells (NSCs) specifically into glutamate-responsive neurons and two morphological distinctive astroglia cell types. H-IL-6-activated neurogenesis seems to be induced by the MAPK/CREB (mitogen-activated protein kinase/cAMP response element-binding protein) cascade, whereas gliogenesis is mediated via the STAT-3 (signal transducers and activators of transcription protein-3) signaling pathway. Our finding that IL-6 mediates both processes depending on its specific soluble receptor sIL-6R-alpha has implications for the potential treatment of neurodegenerative diseases.

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