Evaluation of the Effects of Butyltin Exposures on Expression of Interleukin 1 Beta and Interleukin 6 in Human Immune Cells
Tributyltin (TBT) and dibutyltin (DBT) are organotin compounds that have been used in a variety of applications; as a result, they have been found in human blood. Butyltins (BTs) can decrease the ability of human natural killer (NK) cells to destroy tumor cells and alter the secretion of pro-inflammatory cytokines tumor necrosis factor alpha (TNFα), interferon gamma (IFNγ), and interleukin 1 beta (IL-1β) from human lymphocytes ex vivo. Alterations of IL-1β and IL-6 levels in human immune cells by BTs are examined. Increasingly reconstituted human immune cell preparations were exposed to concentrations of BTs at various lengths of exposure. In addition, the role of ILβ processing enzyme (Caspase-1), mitogen-activated protein kinases (MAPKs) (p38, p44/42, JNK), and nuclear factor kappa B (NFκB) activation in TBT-induced alterations of IL-1β and IL-6 levels were investigated. Results showed that both TBT and DBT altered IL-1? and IL-6 levels. Higher concentrations of DBT (5 and 2.5 μM) decreased the secretion of IL-1β, while lower concentrations of DBT (0.1 and 0.05 μM) increased the secretion of IL-1β. Significant decreases of IL-6 secretion were seen at the highest concentration of TBT (200 nM) and DBT (5-2.5 μM) while the lower concentrations of DBT (0.05 and 0.1 μM) caused elevation of IL-6 secretion. Caspase 1 and MAPK pathways appear to be utilized by DBT in increasing IL-1β secretion. Studies examining the time course of TBT-induced stimulation of IL-1β and IL-6 production showed that substantial changes in the levels of these cytokines require an incubation of 24 h. TBT relies on the activation of the p44/42 and p38 MAPK signaling pathways to cause increases in IL-1β and IL-6 production. TBT-induced increases in IL-1β and IL-6 at the highest concentration were due to increases in their mRNA. p38 is needed for these TBT-induced increases in IL-1β and IL-6 mRNA. Additional studies were performed to address changes seen in TBT-induced production and the ability of TNFα and IL-1β to stimulate IL-6. These data suggest that BT exposures can disrupt cytokine function which has the potential to affect the inflammatory response and immune competence thus leading to predisposition to chronic illness.
Shyretha D Brown,
"Evaluation of the Effects of Butyltin Exposures on Expression of Interleukin 1 Beta and Interleukin 6 in Human Immune Cells"
ETD Collection for Tennessee State University.