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Immun Ageing. 2014 Nov 30;11(1):17. doi: 10.1186/s12979-014-0017-5. eCollection 2014.

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

Author information

1
Jena Centre for Systems Biology of Ageing- JenAge, Jena, Germany ; Leibniz Institute for Age Research, Fritz Lipmann Institute, Beutenbergstrasse 11, D-07745 Jena, Germany.
2
School of Science, University of the West of Scotland, Paisley Campus, Paisley, Scotland PA1 2BE UK.
3
Leibniz Institute for Age Research, Fritz Lipmann Institute, Beutenbergstrasse 11, D-07745 Jena, Germany.
4
Tübingen Ageing and Tumour Immunology Group, Center for Medical Research, University of Tübingen Clinical School, Waldhörnlestr. 22, D-72072 Tübingen, Germany.
5
School of Science and Technology, College of Arts and Science, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS England UK.

Abstract

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.

KEYWORDS:

DNA damage; ERK; Ebselen; GSH:GSSG ratio; Immunosenescence; JNK; Lifespan; MAP kinases; NAC; Proliferative capacity; SENIEUR; Total glutathione; p38

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