Interferon-gamma promotes differentiation of neural progenitor cells via the JNK pathway

Neurochem Res. 2007 Aug;32(8):1399-406. doi: 10.1007/s11064-007-9323-z. Epub 2007 Apr 6.


It has been reported that interferon-gamma (IFN-gamma) facilitates differentiation of PC-12 cells and murine adult neural stem cells. Here we show that IFN-gamma promotes the differentiation of C17.2 neural progenitor cells (NPC) into a neuronal phenotype characterized by neurite outgrowth and the expression of the neuronal marker protein beta-III tubulin. IFN-gamma induced an increase in the activity c-jun N-terminal kinase (JNK) without affecting activities of extracellular signal-regulated kinases (ERKs 1 and 2). An inhibitor of JNK blocked the ability of IFN-gamma to promote differentiation of NPC into neurons, whereas an inhibitor of ERKs 1 and 2 did not. Our findings show that the pro-inflammatory cytokine, IFN-gamma has the potential to stimulate neurogenesis, suggesting roles for this cytokine in development and repair of the nervous system.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Cell Line
  • Cell Proliferation
  • Enzyme Inhibitors / metabolism
  • Interferon-gamma / metabolism*
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • MAP Kinase Signaling System / physiology*
  • Mice
  • Neurons / cytology
  • Neurons / physiology*
  • Phenotype
  • Stem Cells / physiology*


  • Enzyme Inhibitors
  • Interferon-gamma
  • JNK Mitogen-Activated Protein Kinases