Persistent TNF-alpha exposure impairs store operated calcium influx in CD4+ T lymphocytes

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Persistent TNF-alpha exposure impairs store operated calcium influx in CD4+ T lymphocytes. / Church, Leigh; Goodall, John; Rider, DA; Bacon, Paul; Young, Stephen.

In: FEBS Letters, Vol. 579, 28.02.2005, p. 1539-1544.

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@article{dd6621e4a6064aa8a3abdaa6ab9fdb8f,
title = "Persistent TNF-alpha exposure impairs store operated calcium influx in CD4+ T lymphocytes",
abstract = "Persistent tumour necrosis factor alpha (TNF-alpha) exposure uncouples proximal T-cell receptor (TCR)-signalling events. Here, we demonstrate that chronic TNF-alpha exposure also attenuates signalling distal to the TCR, by specifically inhibiting Ca2+ influx evoked by thapsigargin in CD4+ T-cells. Mitogen-induced Ca2+ responses were impaired in a dose dependent manner, and TCR-induced Ca2+ responses were also significantly reduced. The impairment of Ca2+ influx strongly correlated with poor function as proliferative responses to both mitogen and anti-CD3/CD28 stimulation were suppressed. Our findings show that persistent TNF-alpha exposure of T-cells specifically inhibits store operated Ca2+ influx. This may affect gene activation and contribute to the poor T-cell function in chronic inflammatory disease. (C) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.",
keywords = "calcium (Ca2+), T-cell, T-cell receptor, tumour necrosis factor-alpha, store operated Ca2+ influx",
author = "Leigh Church and John Goodall and DA Rider and Paul Bacon and Stephen Young",
year = "2005",
month = feb,
day = "28",
doi = "10.1016/j.febslet.2005.01.051",
language = "English",
volume = "579",
pages = "1539--1544",
journal = "FEBS Letters",
issn = "0014-5793",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Persistent TNF-alpha exposure impairs store operated calcium influx in CD4+ T lymphocytes

AU - Church, Leigh

AU - Goodall, John

AU - Rider, DA

AU - Bacon, Paul

AU - Young, Stephen

PY - 2005/2/28

Y1 - 2005/2/28

N2 - Persistent tumour necrosis factor alpha (TNF-alpha) exposure uncouples proximal T-cell receptor (TCR)-signalling events. Here, we demonstrate that chronic TNF-alpha exposure also attenuates signalling distal to the TCR, by specifically inhibiting Ca2+ influx evoked by thapsigargin in CD4+ T-cells. Mitogen-induced Ca2+ responses were impaired in a dose dependent manner, and TCR-induced Ca2+ responses were also significantly reduced. The impairment of Ca2+ influx strongly correlated with poor function as proliferative responses to both mitogen and anti-CD3/CD28 stimulation were suppressed. Our findings show that persistent TNF-alpha exposure of T-cells specifically inhibits store operated Ca2+ influx. This may affect gene activation and contribute to the poor T-cell function in chronic inflammatory disease. (C) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

AB - Persistent tumour necrosis factor alpha (TNF-alpha) exposure uncouples proximal T-cell receptor (TCR)-signalling events. Here, we demonstrate that chronic TNF-alpha exposure also attenuates signalling distal to the TCR, by specifically inhibiting Ca2+ influx evoked by thapsigargin in CD4+ T-cells. Mitogen-induced Ca2+ responses were impaired in a dose dependent manner, and TCR-induced Ca2+ responses were also significantly reduced. The impairment of Ca2+ influx strongly correlated with poor function as proliferative responses to both mitogen and anti-CD3/CD28 stimulation were suppressed. Our findings show that persistent TNF-alpha exposure of T-cells specifically inhibits store operated Ca2+ influx. This may affect gene activation and contribute to the poor T-cell function in chronic inflammatory disease. (C) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

KW - calcium (Ca2+)

KW - T-cell

KW - T-cell receptor

KW - tumour necrosis factor-alpha

KW - store operated Ca2+ influx

UR - http://www.scopus.com/inward/record.url?scp=14244260521&partnerID=8YFLogxK

U2 - 10.1016/j.febslet.2005.01.051

DO - 10.1016/j.febslet.2005.01.051

M3 - Article

C2 - 15733870

VL - 579

SP - 1539

EP - 1544

JO - FEBS Letters

JF - FEBS Letters

SN - 0014-5793

ER -