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

Immunity & Ageing

Yvonne Barnett²  Graham Pawelec¹  Susanne Steinbrecht³  Robin Freeburn⁴  Shiva Marthandan³ 

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

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

Others  :  1133790
DOI  :  10.1186/s12979-014-0017-5

 received in 2014-09-29, accepted in 2014-11-05,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Marthandan et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

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