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The Time Course Effects of Tributyltin Exposures on eIF4E, eIF4B, and S6 in Human Immune Cells
Author(s) -
Ruff Amanda,
Whalen Margaret
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.01797
Subject(s) - tributyltin , immune system , inflammation , tumor necrosis factor alpha , cytokine , monocyte , eif4e , immunology , interleukin , pharmacology , chemistry , medicine , biochemistry , messenger rna , organic chemistry , translation (biology) , gene
Tributyltin is an environmental contaminant used in a variety of applications. It has been utilized in the preservation of wood, controlling of slime in paper mills, and most notably as an antifouling agent for ships. Due to its multiple uses in various industries, it has entered the food chain and has been detected in human blood at levels as high as 261 nm. 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, rheumatoid arthritis, Crohn's disease, atherosclerosis, and cancer. TBT can increase the synthesis of pro‐inflammatory cytokines such as interferon gamma (IFNγ), tumor necrosis factor alpha (TNFα), interleukin 1 beta (IL‐1β), and interleukin 6 (IL‐6) in human immune cells. TBT appears to utilize 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 (activation) of eukaryotic initiation factor 4E (eIF4E), eIF4B, and the S6 ribosomal subunit. The current study examines the levels and phosphorylation state of eIF4E, eIF4B and S6K after 10‐minute, 1‐hour, 6‐hour, and 24‐hour exposures to TBT in monocyte‐depleted peripheral blood mononuclear cells (MD‐PBMCs). Results indicate that TBT (at several concentrations) caused increased phosphorylation (activation) of eIF4B (S406) and S6 within 10 minutes of exposure across most donors. Within 1 hour of exposure, TBT elevated levels of phospho (P)‐S6, S6, P‐eIF4B (S406) and eIF4B. At 6 hours of exposure TBT caused significant increases at higher concentrations for P‐S6 and P‐eIF4B (S406) and at 24‐hour exposure TBT caused increased levels of S6 and P‐eIF4B (S406). These results suggest that TBT is elevating the synthesis of key pro‐inflammatory cytokines in immune cells by its ability to activate translation.