Hexabromocyclododecane and Tetrabromobisphenol A alter secretion of interferon gamma (IFNγ) from human immune cells
Hexabromocyclododecane (HBCD) and TetrabromobisphenolA (TBBPA) are brominated flame retardant compounds. HBCD is used in polystyrene insulation, accumulates in living organisms and is highly toxic to aquatic organisms. TBBPA is mainly used in plastic, epoxy resin printed circuit board, and other electronic equipment. Interferon gamma (IFNγ) is an inflammatory cytokine that is produced by activated T cells and NK cells and regulates immune responsiveness. HBCD and TBBPA have been found in human blood and previous studies have shown that they alter the ability of human natural killer (NK) lymphocytes to destroy tumor cells. This study examines whether HBCD and TBBPA affect the secretion of IFNγ from human purified NK cells, monocyte-depleted (MD) human peripheral blood mononuclear cells (PBMCs), and PBMCs. IFNγ secretion was measured by enzyme linked immunosorbent assay (ELISA). Results indicate that exposures of NK cells, MD-PBMCs and PBMCs to different concentrations of HBCD and TBBPA (ranging from5-0.05 μM) for 24h, 48h, and 6 days influence the ability of immune cells to secrete IFNγ. Certain concentrations of HBCD caused increases in IFNγ secretion after 24 and 48 h exposures (all cell preparations). However, TBBPA decreases secretion of IFNγ from NK cells and MD-PBMCs but at certain concentrations is able to increase secretion of IFNγ from PBMCs. Thus, exposure to these compounds may potentially disrupt the immune regulation mediated by IFNγ. MD-PBMCs were further studied to determine the mechanism of HBCD induced increases in IFNγ secretion. A variety of signaling pathways like mitogen-activated protein kinases (MAPKs), nuclear factor kappa B (NFêB), MEK (P44/P42), and P38 participate in HBCD-induced increases in IFNγ secretion. Results showed that MAPK pathways (p44/42 and p38) appear to be the targets of HBCD which lead to increased IFNγ secretion from human immune cells.
Haifa M Almughamsi,
"Hexabromocyclododecane and Tetrabromobisphenol A alter secretion of interferon gamma (IFNγ) from human immune cells"
ETD Collection for Tennessee State University.