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: Jodi R. Schilz, Erica J. Dashner-Titus, Li Luo, Karen A. Simmons, Debra A. MacKenzie, Laurie G. Hudson
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Lenguaje:EN
Publicado: Elsevier 2021
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Acceso en línea:https://doaj.org/article/44c8671c56b640f9b37012ae77a6ee2a
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spelling oai:doaj.org-article:44c8671c56b640f9b37012ae77a6ee2a2021-12-04T04:34:22ZCo-exposure of sodium arsenite and uranyl acetate differentially alters gene expression in CD3/CD28 activated CD4+ T-cells2214-750010.1016/j.toxrep.2021.11.019https://doaj.org/article/44c8671c56b640f9b37012ae77a6ee2a2021-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2214750021002031https://doaj.org/toc/2214-7500Communities 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.Jodi R. SchilzErica J. Dashner-TitusLi LuoKaren A. SimmonsDebra A. MacKenzieLaurie G. HudsonElsevierarticleUraniumArsenicT-lymphocytesMixture toxicologyToxicology. PoisonsRA1190-1270ENToxicology Reports, Vol 8, Iss , Pp 1917-1929 (2021)
institution DOAJ
collection DOAJ
language EN
topic Uranium
Arsenic
T-lymphocytes
Mixture toxicology
Toxicology. Poisons
RA1190-1270
spellingShingle Uranium
Arsenic
T-lymphocytes
Mixture toxicology
Toxicology. Poisons
RA1190-1270
Jodi R. Schilz
Erica J. Dashner-Titus
Li Luo
Karen A. Simmons
Debra A. MacKenzie
Laurie G. Hudson
Co-exposure of sodium arsenite and uranyl acetate differentially alters gene expression in CD3/CD28 activated CD4+ T-cells
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.
format article
author Jodi R. Schilz
Erica J. Dashner-Titus
Li Luo
Karen A. Simmons
Debra A. MacKenzie
Laurie G. Hudson
author_facet Jodi R. Schilz
Erica J. Dashner-Titus
Li Luo
Karen A. Simmons
Debra A. MacKenzie
Laurie G. Hudson
author_sort Jodi R. Schilz
title 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_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_sort co-exposure of sodium arsenite and uranyl acetate differentially alters gene expression in cd3/cd28 activated cd4+ t-cells
publisher Elsevier
publishDate 2021
url https://doaj.org/article/44c8671c56b640f9b37012ae77a6ee2a
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