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Oxidative Stress and Neuroprotection pp 45–51Cite as

Apoptosis inhibition in T cells triggers the expression of proinflammatory cytokines — implications for the CNS

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Part of the book series: Journal of Neural Transmission. Supplementa ((NEURALTRANS,volume 71))

Summary

Stimulation of death receptors such as CD95 or TNF-R1 results in rapid onset of apoptosis. Here we show that inhibition of death receptor-induced apoptosis by the broad range caspase inhibitor ZVAD causes a switch from apoptotic to proinflammatory signaling. In previous studies we have reported that caspase inhibitors induce expression of various proin-flammatory cytokines in CD95-stimulated primary T cells, such as TNF-α, IFN-γ and GM-CSF. In this study we provide further evidence for the proinflammatory activity of CD95. Stimulation of CD95 by agonistic antibodies (7C11) resulted in expression of IL-2 in primary T cells, which was further enhanced when caspase activity was blocked by ZVAD. Moreover, CD95 triggered expression of IL-4 and IL-8 when caspase activity was inhibited, but not in the absence of ZVAD. Our findings are of significant importance for the CNS as changes in the cytokine pattern in the periphery affects the entry of various immune cells into the brain. Moreover, invading activated T cells can also directly influence the cytokine profile within the brain, triggering signaling cascades that eventually lead to neuronal cell death. The use of caspase inhibitors to prevent apoptotic cell death should be carefully evaluated in the management of systemic and CNS diseases.

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Authors and Affiliations

  1. Institute of Virology and Immunobiology, Versbacher Strasse 7, 97078, Würzburg, Germany

    Dr. C. Scheller & E. Koutsilieri

  2. Department of Psychiatry and Psychotherapy, Clinical Neurochemistry and NPF Center of Excellence Laboratories, USA

    P. Riederer & E. Koutsilieri

  3. Clinical Neurobiology, Department of Child and Adolescent Psychiatry, Julius-Maximilians-University, Würzburg, Germany

    M. Gerlach

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  1. Dr. C. Scheller
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  2. P. Riederer
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  3. M. Gerlach
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  4. E. Koutsilieri
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Editors and Affiliations

  1. Institute Alfred Fessard de Neurosciences, CNRS, Gif Yvette, France

    H. Parvez

  2. Klinik und Poliklinik für Psychiatrie und Psychotherapie, Würzburg, Germany

    P. Riederer

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© 2006 Springer-Verlag

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Scheller, C., Riederer, P., Gerlach, M., Koutsilieri, E. (2006). Apoptosis inhibition in T cells triggers the expression of proinflammatory cytokines — implications for the CNS. In: Parvez, H., Riederer, P. (eds) Oxidative Stress and Neuroprotection. Journal of Neural Transmission. Supplementa, vol 71. Springer, Vienna. https://doi.org/10.1007/978-3-211-33328-0_6

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  • DOI: https://doi.org/10.1007/978-3-211-33328-0_6

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  • Online ISBN: 978-3-211-33328-0

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