Activation of translation regulatory factor eIF4B in peripheral blood mononuclear cells by tributyltin

Abstract

Tributyltin (TBT) is an organotin that widely contaminates the environment due to multiple uses, primarily as an anti-fouling agent to prevent the growth of organisms on the hull of boats and ships. Due to these uses and a variety of others, TBT has entered the human food chain and has been found in human blood at concentrations as high as 261 nm. Inflammatory cytokines are imperative mediators in response to an injury or infection. If the levels of inflammatory cytokines are increased without a need, they can lead to chronic inflammation. Chronic inflammation has been associated with several pathologies such as rheumatoid arthritis, Crohn's disease, and cancer. Previous studies have shown that TBT can increase the synthesis of pro-inflammatory cytokines interferon gamma (IFNγ), tumor necrosis factor alpha (TNFα), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) in human immune cells. TBT seems to utilize the ERK 1/2 and/or p38 MAPK pathways to stimulate pro-inflammatory cytokine production by immune cells. MAPK pathways have the ability to regulate translation and more specifically processes that can lead to the phosphorylation/activation of eukaryotic initiation factor 4B (eIF4B). The current study examines the levels and phosphorylation state of eIF4B after 10-minute exposures to TBT in peripheral blood mononuclear cells (PBMCs). Initial results indicate that TBT causes increased phosphorylation/ activation of P-eIF4B (S406) at all concentrations and P-eIF4B (S422) at the lowest concentration (2.5 nm). Results suggest that TBT may, at least in part, increase production of pro-inflammatory cytokines in PBMCs due to its ability to activate translation.