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Interferon-α Promotes Survival of Human Primary B-Lymphocytes via Phosphatidylinositol 3-Kinase

https://doi.org/10.1006/bbrc.2001.5025Get rights and content

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-α, 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-α 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-α promotes survival of peripheral B-lymphocytes via the PI3-kinase-PKB/Akt pathway. In addition, IFN-α stimulation of anti-IgM activated cells resulted in downregulated expression of the cell cycle inhibitor p27/Kip1.

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    Abbreviations used: BCR, B-cell receptor; BL, Burkitt's lymphoma cell line; FKHR, forkhead; IFN, interferon; IFNAR, type I interferon receptor; IRS, insulin receptor substrate; JAK, janus kinase; PI, propidium iodide; PI3-kinase, phosphatidylinositol 3′-kinase; PKB/Akt, protein kinase B; STAT, signal transducer and activator of transcription; TUNEL, terminal transferase dUTP nucleotide end labelling.

    1

    These authors contributed equally to this work.

    2

    To whom correspondence should be addressed. Fax: +46 (0)90 77 14 20. E-mail: [email protected].

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