Cytokine mediated inhibition of apoptosis in non-transformed T cells and neutrophils can be dissociated from PKB/AKT activation

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@article{22cd7d64edd14abeaf13e81cf8c1f574,
title = "Cytokine mediated inhibition of apoptosis in non-transformed T cells and neutrophils can be dissociated from PKB/AKT 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 the presence 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.",
keywords = "protein kinase B, apoptosis, AKT, granulocyte, interferon",
author = "Dagmar Scheel-Toellner and Ke-Qing Wang and Nico Henriquez and Paul Webb and Rachel Craddock and Darrell Pilling and AN Akbar and Michael Salmon and Janet Lord",
year = "2002",
month = feb,
day = "1",
doi = "10.1002/1521-4141(200202)32:2<486::AID-IMMU486>3.0.CO;2-U",
language = "English",
volume = "32",
pages = "486--493",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag",

}

RIS

TY - JOUR

T1 - Cytokine mediated inhibition of apoptosis in non-transformed T cells and neutrophils can be dissociated from PKB/AKT activation

AU - Scheel-Toellner, Dagmar

AU - Wang, Ke-Qing

AU - Henriquez, Nico

AU - Webb, Paul

AU - Craddock, Rachel

AU - Pilling, Darrell

AU - Akbar, AN

AU - Salmon, Michael

AU - Lord, Janet

PY - 2002/2/1

Y1 - 2002/2/1

N2 - 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 the presence 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.

AB - 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 the presence 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.

KW - protein kinase B

KW - apoptosis

KW - AKT

KW - granulocyte

KW - interferon

U2 - 10.1002/1521-4141(200202)32:2<486::AID-IMMU486>3.0.CO;2-U

DO - 10.1002/1521-4141(200202)32:2<486::AID-IMMU486>3.0.CO;2-U

M3 - Article

C2 - 11828365

VL - 32

SP - 486

EP - 493

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

ER -