Transcriptomics analysis of primary mouse thymocytes exposed to bis(tri-n-butyltin)dioxide (TBTO)

Kol, Sandra W. M. van; Hendriksen, Peter J.M.; Loveren, Henk Van; Peijnenburg, Ad

doi:10.1016/j.tox.2012.03.002

Cited by 17 publications

(11 citation statements)

References 49 publications

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“…The lack of T cell activation and apoptosis induction for both TBTO and DON, and the lack of ER stress induction in DON exposed EL-4 cells is contrary to previous findings in Jurkat cells and mice experiments. 4,5,13,14,36 Apparently, DON exposure in EL-4 cells does not induce ER stress related genes, which might be due to a lack of molecular hubs that link ribotoxic stress to ER stress. However, it cannot be excluded that DON and TBTO induce ER stress in EL-4 cells at the ( post-) translational level.…”

Section: Overview Of the Mode Of Action Of Tbto And Don In El-4 Cellsmentioning

confidence: 98%

“…Genes affected by TBTO or DON in other studies. 4,5,[12][13][14]18 Genes involved in ribosomal function, ER stress, T cell activation and apoptosis…”

Section: Comparative Data Analysismentioning

confidence: 99%

“…The mode of action of TBTO, as identified in human Jurkat T cells 5,15 and primary mouse thymocytes 13 includes induction of ER stress, T cell activation and apoptosis. The mode of action of DON as identified in mouse thymus in vivo 14 and Jurkat T cells includes the induction of ribotoxic stress and RNA related processes followed by ER stress, T cell activation and apoptosis.…”

Section: Genes Involved In Er Stress T Cell Activation and Apoptosismentioning

confidence: 99%

“…16 In mouse primary thymocytes TBTO upregulates genes that are involved in ER stress, NFκB and TNFα pathways, DNA damage, p53 signalling and apoptosis. 13 DON belongs to a class of mycotoxins, trichothecenes, and is a common contaminant of wheat and corn. [26][27][28] DON, which is a hydroxylated form of nivalenol, is produced by the fungus Fusarium sp.…”

Section: Introductionmentioning

confidence: 99%

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The effects of tributyltin oxide and deoxynivalenol on the transcriptome of the mouse thymoma cell line EL-4

et al. 2014

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The main goal of this study was to assess the potential of the mouse thymoma EL-4 cell line in screening for chemical induced immunotoxicity. Therefore, EL-4 cells were exposed to two well-known immunotoxicants, organotin compound tributyltin oxide (TBTO, 0.5 and 1 µM for 3 or 6 h) and the mycotoxin deoxynivalenol (DON, 0.25, 0.5 and 1 µM for 3, 6 or 11 h). Previous studies in human Jurkat T cells and mouse thymus in vivo showed that the primary mode of action of TBTO is induction of endoplasmic reticulum (ER) stress, T cell activation and apoptosis. DON induces ribotoxic stress and, similarly to TBTO, induces ER stress, T cell activation and apoptosis. In the present study, the effects of TBTO and DON on EL-4 mRNA expression were assessed by whole genome microarray analysis. The microarray data were then compared to those obtained with mouse thymuses in vivo, mouse thymocytes in vitro, and CTLL-2 cells and human Jurkat cells in vitro exposed to TBTO or DON. Analysis at the level of gene sets revealed that part of the previously detected modes of action of TBTO and DON were not observed in the EL-4 cell line. In EL-4 cells, TBTO induced genes involved in calcium signalling and ER stress but did not induce genes involved in T cell activation and apoptosis. DON induced RNA related processes and ribosome biogenesis. Furthermore, DON downregulated ER stress, T cell activation and apoptosis which is opposite to the mechanism of DON observed in the mouse thymus in vivo and in Jurkat T cells in vitro. Apparently, EL-4 cells lack factors that are necessary to link ribotoxic stress to ER stress. In addition, of the lack of T cell activation response of EL-4 cells to TBTO is likely due to the fact that these cells are in a constitutively activated state already. Based on the results obtained for TBTO and DON, it can be concluded that the EL-4 cell line has limited value for immunotoxicogenomics based screening. † Electronic supplementary information (ESI) available. See

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Section: Overview Of the Mode Of Action Of Tbto And Don In El-4 Cellsmentioning

confidence: 98%

“…Genes affected by TBTO or DON in other studies. 4,5,[12][13][14]18 Genes involved in ribosomal function, ER stress, T cell activation and apoptosis…”

Section: Comparative Data Analysismentioning

confidence: 99%

Section: Genes Involved In Er Stress T Cell Activation and Apoptosismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The effects of tributyltin oxide and deoxynivalenol on the transcriptome of the mouse thymoma cell line EL-4

et al. 2014

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“…Similarly, occupational exposure to benzene identified CXCL16, ZNF331, JUN and PF4, as potential biomarkers of early responses to benzene in peripheral blood mononuclear cells (PBMC) of six exposed-control pairs (Forrest et al 2005). In vitro exposure to TBTO (bis-[tri-n-butyltin] oxide) by the Jurkat human T-lymphocyte cell line (Katika et al 2011) and mouse thymocytes (van Kol et al 2012) showed significant changes in Atf4, Atf6, Hspa5, Park7 (Dj-1) and Atox1, that are involved in endoplasmic reticulum stress, and in expression of Bax and Bcl2l11 (Bim) associated with apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Exposure to cypermethrin and mancozeb alters the expression profile of THBS1, SPP1, FEZ1 and GPNMB in human peripheral blood mononuclear cells

Mandarapu¹,

Prakhya

2016

Journal of Immunotoxicology

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The complex immune system displays a coordinated transcriptional response to xenobiotic exposure by altering expression of designated transcription factors that, in turn, trigger immune responses. Despite the identification of several transcription factors that contribute to regulatory response, very little is known about the specific role of factors that are triggered due to exposure to obnoxious pesticides. Here, for the first time, alterations in human peripheral blood lymphocyte expression of transcriptional factors -thrombospondin-1 (THBS-1), secretory phospho-protein-1 (SPP-1), glycoprotein non-metastatic-(GPNMB) and fasciculation and elongation factor -1 (FEZ-1), due to in vitro exposure to the crop protection chemicals cypermethrin and mancozeb are reported. Results revealed significant changes in expression profiles due to mancozeb exposure, supporting its immune dysfunction potential; in contrast, cypermethrin exposure did not cause significant changes. Based on these effects on gene expression across the doses tested, it was likely key components of immune mechanisms such as proliferation, cell adhesion, apoptosis and cell activation in human PBMC were affected. Although these data are from in vitro experiments, the results point out the potential role for changes in these factors in the etiology of defective T-cell immune function seen in humans occupationally exposed to crop protection chemicals like mancozeb. These studies suggest the involvement of transcription factors in regulation of pesticide-induced immune dysfunction; these studies also represent a novel approach for identifying potential immune-related dysfunctions due to exposure to pesticides. Further studies are needed to better understand the functional significance of these in vitro findings. ARTICLE HISTORY

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Mode of Action of Organotins in Immune Cells

Hendriksen

Schmeits

Loveren

et al. 2014

Molecular Immunotoxicology

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Transcriptomics analysis of primary mouse thymocytes exposed to bis(tri-n-butyltin)dioxide (TBTO)

Cited by 17 publications

References 49 publications

The effects of tributyltin oxide and deoxynivalenol on the transcriptome of the mouse thymoma cell line EL-4

The effects of tributyltin oxide and deoxynivalenol on the transcriptome of the mouse thymoma cell line EL-4

Exposure to cypermethrin and mancozeb alters the expression profile of THBS1, SPP1, FEZ1 and GPNMB in human peripheral blood mononuclear cells

Mode of Action of Organotins in Immune Cells

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