title: Cytokine-mediated inhibition of apoptosis in non-transformed T cells and neutrophils can be dissociated from protein kinase B activation.
abstract: In the absence of survival-inducing cytokines activated T cells and neutrophils enter apoptosis spontaneously. Phosphatidylinositol 3-kinase (PI3 K) activation and signaling through PKB/AKT have been widely linked to the inhibition of apoptosis by cytokines. Here we have investigated the role of PKB in the inhibition of spontaneous apoptosis of activated human CD4+ T cells and neutrophils. We used a range of cytokines known to induce survival and/or activation of PKB. We found activation of PKB in T cells treated with IL-2 and insulin, and neutrophils cultured with N-formyl-Met-Leu-Phe (fMLP), insulin or granulocyte-macrophage colony-stimulating factor. Insulin did not inhibit apoptosis in neutrophils or T cells and fMLP did not delay neutrophil apoptosis. Intriguingly, IFN-beta induced PI3 K-dependent survival in both cell types, but did not activate PKB. IL-2 mediated rescue of T cells from apoptosis but no induction of proliferation occurred in thepresence of LY294002, an inhibitor of PI3 K, which also blocked subsequent PKB activation. The main role of PI3 K in IL-2-mediated signaling may therefore be in the regulation of proliferation. These findings suggest that activation of PKB and inhibition of apoptosis can be dissociated in cytokine-mediated rescue of non-transformed CD4+ T cells and neutrophils.
authors.affiliation: MRC Centre for Immune Regulation, The Medical School, University of Birmingham, Birmingham B15 2TT, GB.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Scheel-Toellner
authors.forename: Keqing
authors.initials: K
authors.lastname: Wang
authors.forename: Nico V
authors.initials: NV
authors.lastname: Henriquez
authors.forename: Paul R
authors.initials: PR
authors.lastname: Webb
authors.forename: Rachel
authors.initials: R
authors.lastname: Craddock
authors.forename: Darrell
authors.initials: D
authors.lastname: Pilling
authors.forename: Arne N
authors.initials: AN
authors.lastname: Akbar
authors.forename: Mike
authors.initials: M
authors.lastname: Salmon
authors.forename: Janet M
authors.initials: JM
authors.lastname: Lord
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000276:immunology* / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction
chemical_list: D002867:Chromones; D016207:Cytokines; D004791:Enzyme Inhibitors; D007376:Interleukin-2; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C494918:AKT1 protein, human