The effect of interferon-beta on mouse neural progenitor cell survival and differentiation.
Interferon-beta (IFN-beta) is a mainstay therapy for relapse-remitting multiple sclerosis (MS). However, the direct effects of IFN-beta on the central nervous system (CNS) are not well understood. To determine whether IFN-beta has direct neuroprotective effects on CNS cells, we treated adult mouse neural progenitor cells (NPCs) in vitro with IFN-beta and examined the effects on proliferation, apoptosis, and differentiation. We found that mouse NPCs express high levels of IFNalpha/beta receptor (IFNAR). In response to IFN-beta treatment, no effect was observed on differentiation or proliferation. However, IFN-beta treated mouse NPCs demonstrated decreased apoptosis upon growth factor withdrawal. Pathway-specific polymerase chain reaction (PCR) arrays demonstrated that IFN-beta treatment upregulated the STAT 1 and 2 signaling pathway, as well as GFRA2, NOD1, Caspases 1 and 12, and TNFSF10. These results suggest that IFN-beta can directly affect NPC survival, possibly playing a neuroprotective role in the CNS by modulating neurotrophic factors.
Hirsch
Marek
M
Neurology Department, University of Vermont College of Medicine, Burlington, VT 05405, USA.
Knight
Julia
J
Tobita
Mari
M
Soltys
John
J
Panitch
Hillel
H
Mao-Draayer
Yang
Y
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D016899:Interferon-beta / Q000494:pharmacology*; D051379:Mice; D055495:Neurogenesis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D053633:Receptor, Interferon alpha-beta / Q000096:biosynthesis; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology
D018696:Neuroprotective Agents; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta