Interleukin-6 and neural stem cells: more than gliogenesis.
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.
Islam
Omedul
O
Department of Molecular and Cell Biology, School of Biological Sciences, College of Science, Nanyang Technological University, Singapore, Singapore.
Gong
Xiandi
X
Rose-John
Stefan
S
Heese
Klaus
K
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D048430:Cell Shape; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D018091:Receptors, AMPA / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*
D017362:Cyclic AMP Response Element-Binding Protein; D015850:Interleukin-6; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D018091:Receptors, AMPA; D019947:Receptors, Interleukin-6; D011993:Recombinant Fusion Proteins; D050796:STAT3 Transcription Factor; D020928:Mitogen-Activated Protein Kinases