Interferon-alpha promotes survival of human primary B-lymphocytes via phosphatidylinositol 3-kinase

Biochem Biophys Res Commun. 2001 Jun 15;284(3):583-6. doi: 10.1006/bbrc.2001.5025.

Abstract

Signaling pathways for the antiviral and antiproliferative biological effects of type I interferons (IFN) are well established. In this report we demonstrate a novel signaling pathway for IFN-alpha, as it induced rapid phosphorylation of both PKB/Akt and its substrate forkhead. The PI3-kinase inhibitor LY294002 abolished these phosphorylations. PI3-kinase has been implicated in cell survival mediating its effect through the second messenger PIP3 and the subsequent activation of PKB/Akt. We could show that IFN-alpha inhibited spontaneous apoptosis of primary B-lymphocytes, in the absence of a mitogenic stimulus. This effect was inhibited by LY294002. Thus, our data suggests that IFN-alpha promotes survival of peripheral B-lymphocytes via the PI3-kinase-PKB/Akt pathway. In addition, IFN-alpha stimulation of anti-IgM activated cells resulted in downregulated expression of the cell cycle inhibitor p27/Kip1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / enzymology
  • Cell Cycle Proteins / metabolism
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cyclin-Dependent Kinase Inhibitor p27
  • DNA-Binding Proteins / metabolism
  • Down-Regulation
  • Enzyme Activation
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • Humans
  • Immunoglobulin M / immunology
  • Interferon-alpha / pharmacology*
  • Lymphocyte Activation
  • Phosphatidylinositol 3-Kinases / physiology*
  • Phosphorylation / drug effects
  • Protein Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Transcription Factors / metabolism
  • Tumor Suppressor Proteins*

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • Immunoglobulin M
  • Interferon-alpha
  • Proto-Oncogene Proteins
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • AKT1 protein, human
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt