Inhibition of neurosphere proliferation by IFNgamma but not IFNbeta is coupled to neuronal differentiation.
Interferons are produced following neural damage as part of the inflammatory response and may thus affect neural stem cell function. We compared the effects of interferon-gamma and interferon-beta on the proliferation and differentiation of adult murine neural progenitors. Both interferons inhibited neurosphere proliferation due to cell cycle arrest in G1 but only interferon-gamma induced neuronal differentiation. Both interferons induced differential phosphorylation of STAT proteins and a modest and late upregulation of the cell cycle regulator p27 but not several other likely cell cycle regulators. Thus in neural progenitor cells, anti-proliferative effects of interferons are not necessarily linked to differentiation.
Lum
M
M
Centre for Neuroscience, University of Melbourne VIC 3010, Australia.
Croze
E
E
Wagner
C
C
McLenachan
S
S
Mitrovic
B
B
Turnley
A M
AM
D053687:Adult Stem Cells / Q000187:drug effects*; D000704:Analysis of Variance; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry / Q000379:methods; D047468:Immunoprecipitation; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D020547:Lateral Ventricles / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D050791:STAT Transcription Factors / Q000378:metabolism; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism
D050791:STAT Transcription Factors; D014404:Tubulin; C462941:beta3 tubulin, mouse; D016899:Interferon-beta; D007371:Interferon-gamma