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Title: Transcriptome analysis of the human T lymphocyte cell line Jurkat and human peripheral blood mononuclear cells exposed to deoxynivalenol (DON): New mechanistic insights

Abstract

Deoxynivalenol (DON) or vomitoxin is a commonly encountered type-B trichothecene mycotoxin, produced by Fusarium species predominantly found in cereals and grains. DON is known to exert toxic effects on the gastrointestinal, reproductive and neuroendocrine systems, and particularly on the immune system. Depending on dose and exposure time, it can either stimulate or suppress immune function. The main objective of this study was to obtain a deeper insight into DON-induced effects on lymphoid cells. For this, we exposed the human T-lymphocyte cell line Jurkat and human peripheral blood mononuclear cells (PBMCs) to various concentrations of DON for various times and examined gene expression changes by DNA microarray analysis. Jurkat cells were exposed to 0.25 and 0.5 μM DON for 3, 6 and 24 h. Biological interpretation of the microarray data indicated that DON affects various processes in these cells: It upregulates genes involved in ribosome structure and function, RNA/protein synthesis and processing, endoplasmic reticulum (ER) stress, calcium-mediated signaling, mitochondrial function, oxidative stress, the NFAT and NF-κB/TNF-α pathways, T cell activation and apoptosis. The effects of DON on the expression of genes involved in ER stress, NFAT activation and apoptosis were confirmed by qRT-PCR. Other biochemical experiments confirmed that DON activates calcium-dependentmore » proteins such as calcineurin and M-calpain that are known to be involved in T cell activation and apoptosis. Induction of T cell activation was also confirmed by demonstrating that DON activates NFATC1 and induces its translocation from the cytoplasm to the nucleus. For the gene expression profiling of PBMCs, cells were exposed to 2 and 4 μM DON for 6 and 24 h. Comparison of the Jurkat microarray data with those obtained with PBMCs showed that most of the processes affected by DON in the Jurkat cell line were also affected in the PBMCs. -- Highlights: ► The human T cell line Jurkat and human PBMCs were exposed to DON. ► Whole-genome microarray experiments were performed. ► Microarray data indicates that DON affects ribosome and RNA/protein synthesis. ► DON treatment induces ER stress, calcium mediated signaling, NFAT and NF-κB. ► Exposure to DON induces T cell activation, oxidative stress and apoptosis.« less

Authors:
 [1];  [2];  [1];  [2];  [1];  [2];  [3];  [2];  [1];  [2]
  1. RIKILT-Institute of Food Safety, Wageningen University and Research Centre, Wageningen (Netherlands)
  2. Netherlands
  3. Department of Health Risk Analysis and Toxicology, Maastricht University (Netherlands)
Publication Date:
OSTI Identifier:
22215924
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 264; Journal Issue: 1; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; BIOLOGICAL STRESS; BIOSYNTHESIS; CEREALS; CYTOPLASM; DNA; ENDOPLASMIC RETICULUM; FUSARIUM; GENES; LYMPHOCYTES; MITOCHONDRIA; OXIDATION; POLYMERASE CHAIN REACTION; PROTEINS; RNA; TOXICITY; TRANSLOCATION

Citation Formats

Katika, Madhumohan R., Department of Health Risk Analysis and Toxicology, Maastricht University, Centre, Netherlands Toxicogenomics, Hendriksen, Peter J.M., Centre, Netherlands Toxicogenomics, Shao, Jia, Department of Health Risk Analysis and Toxicology, Maastricht University, Centre, Netherlands Toxicogenomics, Loveren, Henk van, National Institute for Public Health and the Environment, Centre, Netherlands Toxicogenomics, Peijnenburg, Ad, and Centre, Netherlands Toxicogenomics. Transcriptome analysis of the human T lymphocyte cell line Jurkat and human peripheral blood mononuclear cells exposed to deoxynivalenol (DON): New mechanistic insights. United States: N. p., 2012. Web. doi:10.1016/J.TAAP.2012.07.017.
Katika, Madhumohan R., Department of Health Risk Analysis and Toxicology, Maastricht University, Centre, Netherlands Toxicogenomics, Hendriksen, Peter J.M., Centre, Netherlands Toxicogenomics, Shao, Jia, Department of Health Risk Analysis and Toxicology, Maastricht University, Centre, Netherlands Toxicogenomics, Loveren, Henk van, National Institute for Public Health and the Environment, Centre, Netherlands Toxicogenomics, Peijnenburg, Ad, & Centre, Netherlands Toxicogenomics. Transcriptome analysis of the human T lymphocyte cell line Jurkat and human peripheral blood mononuclear cells exposed to deoxynivalenol (DON): New mechanistic insights. United States. https://doi.org/10.1016/J.TAAP.2012.07.017
Katika, Madhumohan R., Department of Health Risk Analysis and Toxicology, Maastricht University, Centre, Netherlands Toxicogenomics, Hendriksen, Peter J.M., Centre, Netherlands Toxicogenomics, Shao, Jia, Department of Health Risk Analysis and Toxicology, Maastricht University, Centre, Netherlands Toxicogenomics, Loveren, Henk van, National Institute for Public Health and the Environment, Centre, Netherlands Toxicogenomics, Peijnenburg, Ad, and Centre, Netherlands Toxicogenomics. 2012. "Transcriptome analysis of the human T lymphocyte cell line Jurkat and human peripheral blood mononuclear cells exposed to deoxynivalenol (DON): New mechanistic insights". United States. https://doi.org/10.1016/J.TAAP.2012.07.017.
@article{osti_22215924,
title = {Transcriptome analysis of the human T lymphocyte cell line Jurkat and human peripheral blood mononuclear cells exposed to deoxynivalenol (DON): New mechanistic insights},
author = {Katika, Madhumohan R. and Department of Health Risk Analysis and Toxicology, Maastricht University and Centre, Netherlands Toxicogenomics and Hendriksen, Peter J.M. and Centre, Netherlands Toxicogenomics and Shao, Jia and Department of Health Risk Analysis and Toxicology, Maastricht University and Centre, Netherlands Toxicogenomics and Loveren, Henk van and National Institute for Public Health and the Environment and Centre, Netherlands Toxicogenomics and Peijnenburg, Ad and Centre, Netherlands Toxicogenomics},
abstractNote = {Deoxynivalenol (DON) or vomitoxin is a commonly encountered type-B trichothecene mycotoxin, produced by Fusarium species predominantly found in cereals and grains. DON is known to exert toxic effects on the gastrointestinal, reproductive and neuroendocrine systems, and particularly on the immune system. Depending on dose and exposure time, it can either stimulate or suppress immune function. The main objective of this study was to obtain a deeper insight into DON-induced effects on lymphoid cells. For this, we exposed the human T-lymphocyte cell line Jurkat and human peripheral blood mononuclear cells (PBMCs) to various concentrations of DON for various times and examined gene expression changes by DNA microarray analysis. Jurkat cells were exposed to 0.25 and 0.5 μM DON for 3, 6 and 24 h. Biological interpretation of the microarray data indicated that DON affects various processes in these cells: It upregulates genes involved in ribosome structure and function, RNA/protein synthesis and processing, endoplasmic reticulum (ER) stress, calcium-mediated signaling, mitochondrial function, oxidative stress, the NFAT and NF-κB/TNF-α pathways, T cell activation and apoptosis. The effects of DON on the expression of genes involved in ER stress, NFAT activation and apoptosis were confirmed by qRT-PCR. Other biochemical experiments confirmed that DON activates calcium-dependent proteins such as calcineurin and M-calpain that are known to be involved in T cell activation and apoptosis. Induction of T cell activation was also confirmed by demonstrating that DON activates NFATC1 and induces its translocation from the cytoplasm to the nucleus. For the gene expression profiling of PBMCs, cells were exposed to 2 and 4 μM DON for 6 and 24 h. Comparison of the Jurkat microarray data with those obtained with PBMCs showed that most of the processes affected by DON in the Jurkat cell line were also affected in the PBMCs. -- Highlights: ► The human T cell line Jurkat and human PBMCs were exposed to DON. ► Whole-genome microarray experiments were performed. ► Microarray data indicates that DON affects ribosome and RNA/protein synthesis. ► DON treatment induces ER stress, calcium mediated signaling, NFAT and NF-κB. ► Exposure to DON induces T cell activation, oxidative stress and apoptosis.},
doi = {10.1016/J.TAAP.2012.07.017},
url = {https://www.osti.gov/biblio/22215924}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 264,
place = {United States},
year = {Mon Oct 01 00:00:00 EDT 2012},
month = {Mon Oct 01 00:00:00 EDT 2012}
}