Effects of Environmental Contaminant Exposures on Translational Regulatory Proteins in Human Immune Cells
Environmental contaminant exposures occur due to the widespread use of synthetic chemicals. TBT and PCP are used in antifouling paints while DBT is used in plastic stabilizers. Due to the multiple uses of TBT, DBT, and PCP, they have been found in human blood and tissue at measurable levels. Inflammatory cytokines are important mediators of the response to injury or infection. However, if their levels are increased in the absence of a needed immune response, chronic inflammation can occur. Chronic inflammation is associated with a number of pathologies including cancer. These environmental toxins appear to use the ERK 1/2 and/or p38 MAPK pathways to stimulate pro-inflammatory cytokine production by immune cells. MAPK pathways have the capacity to regulate translation including processes leading to the phosphorylation of (eIF4E), eIF4B, and S6 ribosomal subunit. The current study observes the levels of eIF4E, eIF4B and S6 after 10-minute, 1-hour, 6-hour, and 24-hour exposures to TBT, DBT, and PCP in PBMCs. Results indicate that all toxins, at several concentrations and varying exposure times, caused a significant increase in the intracellular levels of P-eIF4B (S406) and P-S6 in immune cells. Most increases were observed in 6-hour exposures. P-eIF4E intracellular levels increased the least in comparison to other protein. These results suggest that TBT, DBT, and PCP are capable of elevating the synthesis of pro-inflammatory cytokines in immune cells by their ability to activate translation in one or more key translational factors and more-specifically, that activation of translation may be occurring in a cap-independent manner.
Molecular biology|Immunology|Cellular biology
Amanda E Ruff,
"Effects of Environmental Contaminant Exposures on Translational Regulatory Proteins in Human Immune Cells"
ETD Collection for Tennessee State University.