Bimodal effect of interferon-β on astrocyte proliferation and survival: Importance of nuclear factor-κB

J Neuroimmunol. 2010 Sep 14;226(1-2):73-80. doi: 10.1016/j.jneuroim.2010.05.036. Epub 2010 Jun 25.

Abstract

Accumulating evidence indicates that interferon-β (IFN-β) can modify the complex immunopathogenic scenario causing clinical relapse activity and disease progression in MS. However, the beneficial effects of IFN-β in MS patients may also depend on non-immune mechanisms, including the modulation of astrocyte function. In the present report, we have shown that, depending on the dose, IFN-β treatment can either promote astrocyte proliferation and survival, or result astrocyte death. These actions depend, at least in part, on the regulation of nuclear factor-kappa B (NF-κB), an inducible transcription factor present in neurons and glia. This bimodal effect of IFN-β adds a new layer of complexity in the actions of IFN-β within the CNS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology
  • Animals
  • Apoptosis / drug effects*
  • Astrocytes / drug effects*
  • Bromodeoxyuridine / metabolism
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Dose-Response Relationship, Drug
  • Embryo, Mammalian
  • Enzyme Inhibitors / pharmacology
  • Immunologic Factors / pharmacology*
  • Interferon-beta / pharmacology*
  • NF-kappa B / metabolism*
  • Oncogene Protein v-akt / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Statistics, Nonparametric

Substances

  • Amino Acid Chloromethyl Ketones
  • Enzyme Inhibitors
  • Immunologic Factors
  • NF-kappa B
  • benzyloxycarbonyl-valyl-aspartic acid fluoromethyl ketone
  • Interferon-beta
  • Oncogene Protein v-akt
  • Bromodeoxyuridine