Effects of flame retardants, hexabromocyclododecane (HBCD) and tetrabromobisphenol a (TBBPA), on secretion of tumor necrosis factor alpha (TNFα) from human immune cells
Flame retardants are compounds used in manufactured materials, such as textiles and plastics. Hexabromocyclododecane (HBCD) is a brominated cyclic alkane used primarily as an additive flame retardant, while tetrabromobisphenol A (TBBPA) is a reactive flame retardant. Both are extremely hydrophobic compounds and have a high potential for bioaccumulation. They contaminate the environment and are found in human blood samples. The human immune system protects against invasion by pathogens and the development of cancer. Tumor necrosis factor alpha (TNFα) is a cytokine that is produced by immune cells. It is essential for appropriate immune system communication but can cause chronic inflammation if levels become too high. Previously, HBCD and TBBPA have been shown to alter the tumor killing function of natural killer lymphocytes and it was hypothesized that they may disrupt other immune functions such as the capacity to secrete cytokines. The current study examines the effects of HBCD and TBBPA on secretion of TNFα from human immune cells. Preparations of human immune cell including natural killer (NK) cells, monocyte-depleted (MD) peripheral blood mononuclear cells (PBMCs) (containing both lymphocytes and monocytes) and PBMCs were exposed to either HBCD or TBBPA (5- 0.05 μM) for 24 h, 48 h and 6 days. Following the exposures, levels of TNFα secretion were measured by ELISA. Exposures of immune cells to most concentrations of TBBPA for 24 h, 48h and 6 d decreased the secretion of TNFα from all immune cell preparations, although there was significant variation in the response which was donor dependent. Exposure to certain concentrations of HBCD for 24 h and 48 h caused increased secretion of TNFα in immune cells from some donors. The results indicate that both HBCD and TBBPA are able to alter secretion of TNFα from human immune cells. Thus, these compounds have the potential to disrupt TNFα-dependent immune cell communication as well as influence chronic inflammation. The signaling pathways involved in HBCD-induced increases in TNFα secretion were also examined and it appears that the p38 MARK pathway is needed for HBCD-induced increases in TNFα secretion.
"Effects of flame retardants, hexabromocyclododecane (HBCD) and tetrabromobisphenol a (TBBPA), on secretion of tumor necrosis factor alpha (TNFα) from human immune cells"
ETD Collection for Tennessee State University.