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Effects of Tributyltin Exposures on Translation Regulation in Human Immune Cells
Author(s) -
Ruff Amanda Elizabeth,
Hamza Nafisa M,
Whalen Margaret M
Publication year - 2019
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.2019.33.1_supplement.476.26
Subject(s) - tributyltin , eif4e , immune system , cytokine , tumor necrosis factor alpha , inflammation , phosphorylation , microbiology and biotechnology , mapk/erk pathway , paracrine signalling , chemistry , biology , immunology , translation (biology) , biochemistry , messenger rna , receptor , organic chemistry , gene
Tributyltin (TBT) contaminates the environment due to its use as a biocide. It is found in human blood (ranging as high as 261 nM). TBT is able to 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. This TBT‐induced increase in pro‐inflammatory cytokines could contribute to chronic inflammation, which is a risk factor for a number of diseases including several cancers. TBT appears to utilize the ERK1/2 and/or p38 MAPK pathways to stimulate pro‐inflammatory cytokine synthesis in 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. We hypothesize that TBT may influence the activation state of these translational regulators as part of its mechanism of increasing cytokine synthesis. Studies to examine the levels and phosphorylation state of eIF4E, eIF4B and S6K after varying lengths of exposure to TBT in monocyte‐depleted peripheral blood mononuclear cells (MD‐PBMCs) were carried out. Initial results suggest that TBT caused increased phosphorylation (activation) of eIF4E and S6. These results may indicate that TBT is elevating the synthesis of key pro‐inflammatory cytokines in immune cells by its ability to activate translation. Support or Funding Information NIH Grant 5U54CA163066 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .