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MBC in Press, published online ahead of print October 29, 2008
Mol. Biol. Cell 10.1091/mbc.E08-05-0463

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Submitted on May 7, 2008
Revised on October 14, 2008
Accepted on October 22, 2008

Interleukin-6 and Neural Stem Cells – More Than Gliogenesis

Omedul Islam,* Alex 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; {dagger}Department of Biochemistry, Christian-Albrechts-University, D-24098 Kiel, Germany

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, while 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.

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






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