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Co-exposure of sodium arsenite and uranyl acetate differentially alters gene expression in CD3/CD28 activated CD4+ T-cells

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 Enviro...

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Autores principales: Schilz, Jodi R., Dashner-Titus, Erica J., Luo, Li, Simmons, Karen A., MacKenzie, Debra A., Hudson, Laurie G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8649082/
https://www.ncbi.nlm.nih.gov/pubmed/34926170
http://dx.doi.org/10.1016/j.toxrep.2021.11.019
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author Schilz, Jodi R.
Dashner-Titus, Erica J.
Luo, Li
Simmons, Karen A.
MacKenzie, Debra A.
Hudson, Laurie G.
author_facet Schilz, Jodi R.
Dashner-Titus, Erica J.
Luo, Li
Simmons, Karen A.
MacKenzie, Debra A.
Hudson, Laurie G.
author_sort Schilz, Jodi R.
collection PubMed
description 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.
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spelling pubmed-86490822021-12-17 Co-exposure of sodium arsenite and uranyl acetate differentially alters gene expression in CD3/CD28 activated CD4+ T-cells Schilz, Jodi R. Dashner-Titus, Erica J. Luo, Li Simmons, Karen A. MacKenzie, Debra A. Hudson, Laurie G. Toxicol Rep Regular Article 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. Elsevier 2021-11-27 /pmc/articles/PMC8649082/ /pubmed/34926170 http://dx.doi.org/10.1016/j.toxrep.2021.11.019 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Regular Article
Schilz, Jodi R.
Dashner-Titus, Erica J.
Luo, Li
Simmons, Karen A.
MacKenzie, Debra A.
Hudson, Laurie G.
Co-exposure of sodium arsenite and uranyl acetate differentially alters gene expression in CD3/CD28 activated CD4+ T-cells
title Co-exposure of sodium arsenite and uranyl acetate differentially alters gene expression in CD3/CD28 activated CD4+ T-cells
title_full Co-exposure of sodium arsenite and uranyl acetate differentially alters gene expression in CD3/CD28 activated CD4+ T-cells
title_fullStr Co-exposure of sodium arsenite and uranyl acetate differentially alters gene expression in CD3/CD28 activated CD4+ T-cells
title_full_unstemmed Co-exposure of sodium arsenite and uranyl acetate differentially alters gene expression in CD3/CD28 activated CD4+ T-cells
title_short Co-exposure of sodium arsenite and uranyl acetate differentially alters gene expression in CD3/CD28 activated CD4+ T-cells
title_sort co-exposure of sodium arsenite and uranyl acetate differentially alters gene expression in cd3/cd28 activated cd4+ t-cells
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8649082/
https://www.ncbi.nlm.nih.gov/pubmed/34926170
http://dx.doi.org/10.1016/j.toxrep.2021.11.019
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