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Organotin and organochlorine toxicants activate key translational regulatory proteins in human immune cells

  • Molecular Toxicology
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Abstract

Environmental contaminant exposures occur due to the widespread use of synthetic chemicals. Tributyltin (TBT), dibutyltin (DBT), and pentachlorophenol (PCP) are each used in a variety of applications, including antifouling paints and stabilizers in certain plastics. Each of these compounds has been found in human blood, as well as other tissues, and they have been shown to stimulate pro-inflammatory cytokine production in human immune cells, Inflammatory cytokines mediate response to injury or infection. However, if their levels are increased in the absence of an appropriate stimulus, chronic inflammation can occur. Chronic inflammation is associated with a number of pathologies including cancer. Stimulation of pro-inflammatory cytokine production by these toxicants is dependent on activation of ERK 1/2 and/or p38 MAPK pathways. MAPK pathways have the capacity to regulate translation by increasing phosphorylation of key translation regulatory proteins. There have been no previous studies examining the effects of TBT, DBT, or PCP on translation. The current study shows that ribosomal protein S6 (S6), eukaryotic initiation factor 4B (eIF4B), and eIF4E are phosphorylated (activated) and/or their total levels are elevated in response to each of these compounds at concentrations found in human blood. Activation/increased levels of translational proteins occurred at concentrations of the compounds that have been shown to elevate pro-inflammatory cytokine production, but where there is no increase in mRNA for those proteins was seen. Compound-stimulated increases in translation appear to be part of the mechanism by which they elevate protein production in immune cells.

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Acknowledgements

Supported by Grant U54CA163066 from the National Institutes of Health.

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  1. Department of Biology, Tennessee State University, Nashville, TN, 37209, USA

    Amanda Ruff & Meaghan Lewis

  2. Department of Chemistry, Tennessee State University, 3500 John A. Merritt Blvd., Nashville, TN, 37209, USA

    Margaret Whalen

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Ruff, A., Lewis, M. & Whalen, M. Organotin and organochlorine toxicants activate key translational regulatory proteins in human immune cells. Arch Toxicol 97, 469–493 (2023). https://doi.org/10.1007/s00204-022-03413-z

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