Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 448526
Title Toxicogenomics-Based Identification of Mechanisms for Direct Immunitoxicity
Author(s) Shao, J.; Katika, M.R.; Schmeits, P.C.; Hendriksen, P.J.M.; Loveren, H. van; Peijnenburg, A.A.C.M.; Volger, O.L.
Source Toxicological sciences 135 (2013)2. - ISSN 1096-6080 - p. 328 - 346.
DOI https://doi.org/10.1093/toxsci/kft151
Department(s) RIKILT - BU Toxicology Bioassays & Novel Foods
Publication type Refereed Article in a scientific journal
Publication year 2013
Keyword(s) unfolded protein response - nf-kappa-b - endoplasmic-reticulum stress - blood mononuclear-cells - liver-x-receptor - proliferator-activated receptor - gene-expression profiles - in-vitro - ochratoxin-a - human-lymphocytes
Abstract Compounds with direct immunotoxic properties, including metals, mycotoxins, agricultural pesticides, and industrial chemicals, form potential human health risks due to exposure through food, drinking water, and the environment. Insights into the mechanisms of action are currently lacking for the majority of these direct immunotoxicants. Therefore, the present work aimed to gain insights into the molecular mechanisms underlying direct immunotoxicity. To this end, we assessed in vitro the effects of 31 test compounds on the transcriptome of the human Jurkat T-cell line. These compounds included direct immunotoxicants, immunosuppressive drugs with different mode of actions, and nonimmunotoxic control chemicals. Pathway analysis of the microarray data allowed us to identify canonical pathways and Gene Ontology processes that were transcriptionally regulated in common by immunotoxicants (1) with structural similarities, such as tributyltin chloride and tributyltin oxide that activated the retinoic acid/X receptor signaling pathway and (2) without structural similarities, such as As2O3, dibutyltin chloride, diazinon, MeHg, ochratoxin A (OTA), S9-treated OTA, S9-treated cyclophosphamide, and S9-treated benzo[a]pyrene, which activated unfolded protein response, and FTY720, lindane, and propanil, which activated the cholesterol biosynthesis pathway. In addition, processes uniquely affected by individual immunotoxicants were identified, such as the induction of Notch receptor signaling and the downregulation of acute-phase response genes by OTA. These findings were validated by quantitative real-time PCR analysis of genes involved in these processes. Our study indicated that diverse modes of action are involved in direct immunotoxicity and that a set of pathways or genes, rather than one single gene, can be used to screen compounds for direct immunotoxicity.
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