Neural precursor cells as a novel target for interferon-beta

The immunomodulating agent interferon-beta (IFN beta) is administered therapeutically in several autoimmune diseases and endogenously released by immune cells during diverse infections. As in recent years a variety of pro- and anti-inflammatory substances were shown to influence significantly neural precursor cells that are implicated in a variety of regenerative mechanisms but also in tumor growth, we studied a possible effect of IFN beta on neural precursor cells derived from murine embryonic day 14 neurospheres. First, we demonstrated that interferon type-I receptors are expressed on neural precursor cells and that these cells respond to IFN beta treatment by up-regulating IFN beta inducible genes including Myxovirus 1 and viperin. Furthermore, we could show for the first time that IFN beta treatment significantly inhibited the proliferation of neural precursor cells possibly through induction of p21, a cyclin-dependent kinase inhibitor. IFN beta did not exert cytotoxic or neuroprotective effects and we could not see effects on the differentiation of neural precursor cells into total amounts of neurons, astrocytes or oligodendrocytes. However, we found that IFN beta markedly diminished neurite outgrowth and neuronal maturation of neural precursor-derived neurons. (c) 2008 Elsevier Ltd. All rights reserved.