The effects of hexabromocyclododecane (HBCD) and tetrabromobisphenol A (TBBPA) on mitogen-activated protein kinases in human natural killer cells
Human natural killer (NK) cells are a subpopulation of lymphocytes that play an important role in both innate and adaptive host immune responses. NK cells provide a vital surveillance against virally infected cells, tumor cells, and antibody-coated cells through the release of cytolytic mediators and gamma interferon (IFN-γ). Unlike T lymphocytes, NK cells destroy appropriate target cells without prior sensitization making them the first line of defense against foreign infections. Hexabromocyclododecane (HBCD) is a brominated flame retardant used primarily in expanded (EPS) and extruded (XPS) polystyrene foams for thermal insulation in the building and construction industry. Tetrabromobisphenol A (TBBPA) is used both as a reactive and an additive flame retardant in a variety of materials. HBCD and TBBPA contaminate the environment and are found in human blood samples. We have shown that other environment contaminants, such as the dibutyltin (DBT) and tributyltin (TBT), decrease NK lytic function by activating mitogen-activated protein kinases (MAPKs) in the NK cells. HBCD and TBBPA also interfere with NK cell(s) lytic function. The current study evaluates whether HBCD and/or TBBPA have the capacity to activate MAPKs and MAP2Ks (mitogen-activated protein kinase kinase). In this study, we examined the effects of concentrations of HBCD and TBBPA that inhibited lytic function on the phosphorylation state and total levels of the MAPKs -p44/42, p38, and JNK - and the phosphorylation and total levels of the MAP2Ks - MEK1/2, MKK3/6 and MKK4. Results indicate that exposure of human NK cells to 10-0.5 µM HBCD and/or TBBPA for 10 minutes, 1 hour and 6 hours increases the phosphorylation (activation) of MAPKs and MAP2Ks. This HBCD and TBBPA-induced phosphorylation of MAPKs may leave them unavailable for activation by virally infected or tumor target cells and thus contributes to the observed decreases in lytic function seen in NK cells exposed to HBCD and TBBPA.
Anita R Cato,
"The effects of hexabromocyclododecane (HBCD) and tetrabromobisphenol A (TBBPA) on mitogen-activated protein kinases in human natural killer cells"
ETD Collection for Tennessee State University.