Co-exposure of sodium arsenite and uranyl acetate differentially alters gene expression in CD3/CD28 activated CD4+ T-cells
| العنوان: | Co-exposure of sodium arsenite and uranyl acetate differentially alters gene expression in CD3/CD28 activated CD4+ T-cells |
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| المؤلفون: | Karen A. Simmons, Li Luo, Erica J. Dashner-Titus, Debra MacKenzie, Laurie G. Hudson, Jodi R. Schilz |
| المصدر: | Toxicology Reports, Vol 8, Iss, Pp 1917-1929 (2021) Toxicology Reports |
| بيانات النشر: | Elsevier BV, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Sodium arsenite, Health, Toxicology and Mutagenesis, CD3, Uranyl acetate, GCLM, glutamate-cysteine ligase, APC, antigen presenting cell, Toxicology, NQO1, NAD(P)H quinone dehydrogenase, Arsenic, SOD1, super oxide dismutase 1, chemistry.chemical_compound, RA1190-1270, DEG, differentially expressed gene, Gene expression, T-lymphocytes, ComputingMethodologies_COMPUTERGRAPHICS, AUM, abandoned uranium mine, Th, T-helper, PCA, principal component analysis, Mixture toxicology, biology, MHC, major histone compatibility complex, CD28, Regular Article, Molecular biology, IFNγ, interferon gamma, chemistry, TCR, T-cell receptor, Toxicology. Poisons, biology.protein, Uranium, IL-2, interleukin 2, Co exposure, HMOX1, heme oxygenase 1 |
| الوصف: | Graphical abstract Highlights • Uranium and arsenic co-occur as contaminants in water sources in the Southwestern US. • Exposure to metals may alter gene expression and cause immune dysregulation in CD4+ T-cells. • RNA-seq analysis on CD4+ T-cells treated with UA prior to activation led to no significant alterations in gene expression. • A mixture of UA and As demonstrated unique alterations in gene expression compared to As alone. Communities in the western region of the United States experience environmental exposure to metal mixtures from living in proximity to numerous unremediated abandoned uranium mines. Metals including arsenic and uranium co-occur in and around these sites at levels higher than the United States Environmental Protection Agency maximum contaminant levels. To address the potential effect of these metals on the activation of CD4+ T-cells, we used RNA sequencing methods to determine the effect of exposure to sodium arsenite (1 μM and 10 μM), uranyl acetate (3 μM and 30 μM) or a mixture of sodium arsenite and uranyl acetate (1 μM sodium arsenite + 3 μM uranyl acetate). Sodium arsenite induced a dose dependent effect on activation associated gene expression; targeting immune response genes at the lower dose. Increases in oxidative stress gene expression were observed with both sodium arsenite doses. While uranyl acetate alone did not significantly alter activation associated gene expression, the mixture of uranyl acetate with sodium arsenite demonstrated a combined effect relative to sodium arsenite alone. The results demonstrate the need to investigate metal and metalloid mixtures at environmentally relevant concentrations to better understand the toxicological impact of these mixtures on T-cell activation, function and immune dysregulation. |
| تدمد: | 2214-7500 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e02ed1fd8c3c4023146cd14f108fc58a https://doi.org/10.1016/j.toxrep.2021.11.019 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e02ed1fd8c3c4023146cd14f108fc58a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22147500 |
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