Interferon beta promotes survival in primary astrocytes through phosphatidylinositol 3-kinase

J Neuroimmunol. 2003 Jun;139(1-2):155-9. doi: 10.1016/s0165-5728(03)00160-7.

Abstract

Although interferon-beta (IFN-beta) has been demonstrated to be effective in the treatment of multiple sclerosis (MS) patients, the mechanism(s) underlying its beneficial effects has not been uncovered yet. Until now, most of the effort in the study of the relevant mechanisms of IFN-beta has dealt with its ability to modulate the immune response. Only recently, it has been proposed that the beneficial effects of IFN-beta in MS patients could depend on its ability to modulate astrocyte function. In the present work, we have found that IFN-beta treatment promotes the survival of astrocytes through stimulation of the phosphatidylinositol 3-kinase (PI-3K)/Akt pathway. We propose that the beneficial effects of IFN-beta in MS therapy may depend, at least in part, on its capacity to protect astrocytes against the apoptotic cell death that occurs in the early steps of the pathogenesis of MS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Astrocytes / drug effects*
  • Astrocytes / enzymology
  • Cell Survival / drug effects*
  • Cell Survival / physiology
  • Cells, Cultured
  • Central Nervous System / drug effects*
  • Central Nervous System / enzymology
  • Central Nervous System / physiopathology
  • Culture Media, Serum-Free / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Fetus
  • Interferon-beta / pharmacology*
  • Interferon-beta / therapeutic use
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / enzymology
  • Multiple Sclerosis / physiopathology
  • Phosphatidylinositol 3-Kinases / drug effects*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / drug effects
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Culture Media, Serum-Free
  • Enzyme Inhibitors
  • Proto-Oncogene Proteins
  • Interferon-beta
  • Akt1 protein, rat
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt