A Time Course Study Examining the Effects of Tributyltin Exposures on eIF4E

Abstract

Tributyltin (TBT) is an environmental contaminant which is found in human blood (ranging as high as 261 nM) and other tissues due to its lipophilic nature, and it has been shown to increase incidences of tumors in mammals. TBT alters secretion of pro‐inflammatory cytokines such as interferon gamma (IFNγ), tumor necrosis factor alpha (TNFα), interleukin 1 beta (IL‐1β), and interleukin 6 (IL‐6) from human lymphocytes. Previous ex vivo studies have shown that when TBT is introduced as a stress inducer to the cellular environment, the production (secretion and/or intracellular levels) of IL‐1β and IL‐6 was increased in human lymphocytes, and ERK1/2 and p38 MAPK pathways were shown to be necessary for this TBT effect. An additional study indicated that TBT‐induced increases in IL‐1β and IL‐6 production cannot be explained by increases in their respective mRNA at concentrations below 50 nM. Thus, further studies were carried out to address whether the changes in IL‐1β and IL‐6 production induced by TBT might be due to alterations of mRNA translation. The ERK1/2 pathway has been noted to catalyze the phosphorylation (activation) of eukaryotic initiation factor 4E (eIF4E), which is a key player of binding the 5′ cap of mRNAs. As previous studies have indicated a role for the ERK1/2 pathway in the TBT‐induced increases in IL‐1β and IL‐6 production, we carried out initial studies to examine the levels and phosphorylation state of eIF4E after 10 min, 30 min, 6 h, and 24 h exposures to TBT in monocyte‐depleted peripheral blood mononuclear cells (MD‐PBMCs) using western blot analysis. Results suggested that increased phosphorylation (activation) of eIF4E was seen after 10 min exposure to TBT and maintained after 24 h exposure. These results may indicate that eIF4E is a key factor for regulating translation when MD‐PBMCs are exposed to TBT.Support or Funding InformationSupported by NIH grant U54CA163066.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.