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SENIEUR status of the originating cell donor negates certain ‘anti-immunosenescence’ effects of ebselen and N-acetyl cysteine in human T cell clone cultures

BACKGROUND: Damage to T cells of the immune system by reactive oxygen species may result in altered cell function or cell death and thereby potentially impact upon the efficacy of a subsequent immune response. Here, we assess the impact of the antioxidants Ebselen and N-acetyl cysteine on a range of...

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Autores principales: Marthandan, Shiva, Freeburn, Robin, Steinbrecht, Susanne, Pawelec, Graham, Barnett, Yvonne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263119/
https://www.ncbi.nlm.nih.gov/pubmed/25505928
http://dx.doi.org/10.1186/s12979-014-0017-5
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author Marthandan, Shiva
Freeburn, Robin
Steinbrecht, Susanne
Pawelec, Graham
Barnett, Yvonne
author_facet Marthandan, Shiva
Freeburn, Robin
Steinbrecht, Susanne
Pawelec, Graham
Barnett, Yvonne
author_sort Marthandan, Shiva
collection PubMed
description BACKGROUND: Damage to T cells of the immune system by reactive oxygen species may result in altered cell function or cell death and thereby potentially impact upon the efficacy of a subsequent immune response. Here, we assess the impact of the antioxidants Ebselen and N-acetyl cysteine on a range of biological markers in human T cells derived from a SENIEUR status donor. In addition, the impact of these antioxidants on different MAP kinase pathways in T cells from donors of different ages was also examined. METHODS: T cell clones were derived from healthy 26, 45 and SENIEUR status 80 year old people and the impact of titrated concentrations of Ebselen or N-acetyl cysteine on their proliferation and in vitro lifespan, GSH:GSSG ratio as well as levels of oxidative DNA damage and on MAP kinase signaling pathways was examined. RESULTS: In this investigation neither Ebselen nor N-acetyl cysteine supplementation had any impact on the biological endpoints examined in the T cells derived from the SENIEUR status 80 year old donor. This is in contrast to the anti-immunosenescent effects of these antioxidants on T cells from donors of 26 or 45 years of age. The analysis of MAP kinases showed that pro-apoptotic pathways become activated in T cells with increasing in vitro age and that Ebselen or N-acetyl cysteine could decrease activation (phosphorylation) in T cells from 26 or 45 year old donors, but not from the SENIEUR status 80 year old donor. CONCLUSIONS: The results of this investigation demonstrate that the biological phenotype of SENIEUR status derived human T cells negates the anti-immunosenescence effects of Ebselen and also N-acetyl cysteine. The results highlight the importance of pre-antioxidant intervention evaluation to determine risk-benefit. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12979-014-0017-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-42631192014-12-12 SENIEUR status of the originating cell donor negates certain ‘anti-immunosenescence’ effects of ebselen and N-acetyl cysteine in human T cell clone cultures Marthandan, Shiva Freeburn, Robin Steinbrecht, Susanne Pawelec, Graham Barnett, Yvonne Immun Ageing Research BACKGROUND: Damage to T cells of the immune system by reactive oxygen species may result in altered cell function or cell death and thereby potentially impact upon the efficacy of a subsequent immune response. Here, we assess the impact of the antioxidants Ebselen and N-acetyl cysteine on a range of biological markers in human T cells derived from a SENIEUR status donor. In addition, the impact of these antioxidants on different MAP kinase pathways in T cells from donors of different ages was also examined. METHODS: T cell clones were derived from healthy 26, 45 and SENIEUR status 80 year old people and the impact of titrated concentrations of Ebselen or N-acetyl cysteine on their proliferation and in vitro lifespan, GSH:GSSG ratio as well as levels of oxidative DNA damage and on MAP kinase signaling pathways was examined. RESULTS: In this investigation neither Ebselen nor N-acetyl cysteine supplementation had any impact on the biological endpoints examined in the T cells derived from the SENIEUR status 80 year old donor. This is in contrast to the anti-immunosenescent effects of these antioxidants on T cells from donors of 26 or 45 years of age. The analysis of MAP kinases showed that pro-apoptotic pathways become activated in T cells with increasing in vitro age and that Ebselen or N-acetyl cysteine could decrease activation (phosphorylation) in T cells from 26 or 45 year old donors, but not from the SENIEUR status 80 year old donor. CONCLUSIONS: The results of this investigation demonstrate that the biological phenotype of SENIEUR status derived human T cells negates the anti-immunosenescence effects of Ebselen and also N-acetyl cysteine. The results highlight the importance of pre-antioxidant intervention evaluation to determine risk-benefit. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12979-014-0017-5) contains supplementary material, which is available to authorized users. BioMed Central 2014-11-30 /pmc/articles/PMC4263119/ /pubmed/25505928 http://dx.doi.org/10.1186/s12979-014-0017-5 Text en © Marthandan et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Marthandan, Shiva
Freeburn, Robin
Steinbrecht, Susanne
Pawelec, Graham
Barnett, Yvonne
SENIEUR status of the originating cell donor negates certain ‘anti-immunosenescence’ effects of ebselen and N-acetyl cysteine in human T cell clone cultures
title SENIEUR status of the originating cell donor negates certain ‘anti-immunosenescence’ effects of ebselen and N-acetyl cysteine in human T cell clone cultures
title_full SENIEUR status of the originating cell donor negates certain ‘anti-immunosenescence’ effects of ebselen and N-acetyl cysteine in human T cell clone cultures
title_fullStr SENIEUR status of the originating cell donor negates certain ‘anti-immunosenescence’ effects of ebselen and N-acetyl cysteine in human T cell clone cultures
title_full_unstemmed SENIEUR status of the originating cell donor negates certain ‘anti-immunosenescence’ effects of ebselen and N-acetyl cysteine in human T cell clone cultures
title_short SENIEUR status of the originating cell donor negates certain ‘anti-immunosenescence’ effects of ebselen and N-acetyl cysteine in human T cell clone cultures
title_sort senieur status of the originating cell donor negates certain ‘anti-immunosenescence’ effects of ebselen and n-acetyl cysteine in human t cell clone cultures
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263119/
https://www.ncbi.nlm.nih.gov/pubmed/25505928
http://dx.doi.org/10.1186/s12979-014-0017-5
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