Abstract
Exposure to the endocrine disruptor bisphenol A (BPA) has been linked with immune disorders and increased tumour risk. Our previous work in activated human peripheral blood mononuclear cells demonstrated that exposure to “low-dose” BPA diminished telomerase activity via an ER/GPR30-ERK signalling pathway. Leukocyte telomerase activity and telomere maintenance are crucial for normal immune function and homeostasis. We thus here further studied the effects of BPA on human T cell subpopulations. Exposure to 0.3–3 nM BPA, i. e. at doses in the realm of human exposure, notably reduced telomerase activity in activated CD8 + T but not CD4 + T cells in a non-monotonic response pattern as determined by the TRAP-ELISA assay. Under long-term BPA exposure, significant telomere length shortening, reduction in mitochondrial DNA copy number, cell proliferation and IFN-γ as well as hTERT protein suppression could be observed in CD8 + lymphocytes, as analysed by qRT-PCR, flow cytometry and western blot analysis. This study extends our previous in vitro findings that “low-dose” BPA has potential negative effects on healthy human cytotoxic T cell response. These results might merit some special attention to further investigate chronic BPA exposure in the context of adaptive immune response dysfunction and early onset of cancer in man.
Highlights
Bisphenol A (BPA) is a plasticizer used for the production of food contact applications in such a wide range that daily “low-dose” exposure to this compound is inevitable
Telomerase plays a critical role in the regulation of immune cell function and to further discern our previously reported findings on telomerase activity inhibition by bisphenol A (BPA) in CD3/CD28 stimulated PBMC7, we here first investigated the effect of BPA on telomerase in CD4 + and CD8 + T cell subpopulations
Shortened leukocyte telomere length and telomerase activity dysfunction have been linked with increased mortality and age-related disorders including c ancer[27,28,37]
Summary
Bisphenol A (BPA) is a plasticizer used for the production of food contact applications in such a wide range that daily “low-dose” exposure to this compound is inevitable. Using animals and humanized animal models, Prins et al.[13,14,15] proposed that “low-dose” BPA exposure may enhance the cancer risk with ageing, and reduce tumour sensitivity to treatment which is in line with reported cell-based studies[16,17]. Altered telomerase enzyme activity as well as short telomeres have been proposed as risk factors for immune system dysfunction[27,28]. This in turn may contribute to initiation of malignant tumour formation[29]. Our previous study reported on the potential negative impact of “low-dose” BPA exposure on human PBMC via persistent down-regulation of telomerase a ctivity[7]. Longterm treatment significantly diminished cell proliferation, telomere length, mitochondrial DNA (mtDNA) copy number and anti-viral IFN-γ production
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