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Originally published as MBC in Press, 10.1091/mbc.E08-05-0463 on October 29, 2008

Vol. 20, Issue 1, 188-199, January 1, 2009

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Interleukin-6 and Neural Stem Cells: More Than Gliogenesis

Omedul Islam*, Xiandi Gong*, Stefan Rose-John{dagger}, and Klaus Heese*

*Department of Molecular and Cell Biology, School of Biological Sciences, College of Science, Nanyang Technological University, Singapore 637551, Singapore; and {dagger}Department of Biochemistry, Christian-Albrechts University, D-24098 Kiel, Germany

Submitted May 7, 2008; Revised October 14, 2008; Accepted October 22, 2008
Monitoring Editor: Carl-Henrik Heldin

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.

This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E08-05-0463) on October 29, 2008.

Address correspondence to: Klaus Heese (kheese{at}ntu.edu.sg).






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