Interferon-alpha promotes survival of human primary B-lymphocytes via phosphatidylinositol 3-kinase.
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.
Ruuth
K
K
Department of Cell and Molecular Biology, Umeå University, 901 87 Umeå, Sweden.
Carlsson
L
L
Hallberg
B
B
Lundgren
E
E
D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D018797:Cell Cycle Proteins / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation; D004789:Enzyme Activation; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D016898:Interferon-alpha / Q000494:pharmacology*; D008213:Lymphocyte Activation; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004268:DNA-Binding Proteins; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D007075:Immunoglobulin M; D016898:Interferon-alpha; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C085126:FOXO1 protein, human; C494918:AKT1 protein, human