Assessment of the Effects of Butyltin Environmental Contaminants on Human and Mouse Cytokine Production and Secretion from Immune Cells
The extensive utilization of butyltins (BTs) has led to global contamination and their bioaccumulation in aquatic organisms and terrestrial mammals. In this study, the dysregulation of IFNγ and TNFα levels in human immune cells by BTs is examined. Increasingly reconstituted immune cell populations were exposed to concentrations of BTs at varied lengths of exposures. In addition, the role of TACE, p38, p44/42, JNK MAPKs and NFκB activation in TBT-induced alterations of IFNγ and TNFα levels were investigated. MD-PBMCs were exposed to appropriate pathway inhibitors and western blot and ELISA assay used to determine TBT-induced cytokine production after 24 h. The serum of TBT-exposed mice was analyzed for changes in the levels of cytokine secretion and production using a MagPix assay and western blot; the effects of TBT-exposure was assessed using a time curve of 6 h, 12 h, 24 h, 48 h and control. When human NK cells, MD-PBMCs and PBMCs were exposed to 0-200 nM TBT and 0-5 μM DBT, results showed a significant TBT-induced stimulation in all cell types. However, the effective concentration of the compound needed to cause increases varied among donors. Studies examining the time course of TBT-induced stimulation of IFNγ and TNFα production, indicate that substantial changes in the levels of these cytokines require an incubation of 24 h. TBT heavily relies on activation of the p38 signaling pathway to cause increases in IFNγ and TNFα, as diminished cytokine levels were seen in all donors after inhibition of this pathway. TBT-induced alterations were observed in IFNγ, TNFα, IL1β, IL-2, IL5, IL12βp40, and IL-15 after mice were exposed to biologically relevant concentrations of TBT. Increases in IFNγ, TNFα and IL-12βp40 were seen in the serum of mice exposed to TBT for less than 24 h. IL-5 and IL-15 were both increased and decreased in mouse serum depending on the specific experiment and the exposure concentration. IL-1β and IL-2 were consistently decreased in mouse serum when animals were exposed to TBT. These data suggest that BT exposures can dysregulate cytokine signaling, thus promoting an inflammatory environment, which could predispose the host to various immunopathologies.
Molecular biology|Cellular biology|Biochemistry
Shanieek T Lawrence,
"Assessment of the Effects of Butyltin Environmental Contaminants on Human and Mouse Cytokine Production and Secretion from Immune Cells"
ETD Collection for Tennessee State University.