Tetrabromobisphenol a and hexabromocyclododecane alter the secretion of interleukin 1 beta (IL-1beta) from human immune cells
Tetrabromobisphenol A (TBBPA) and Hexabromocyclododecane (HBCD), flame retardants usually used in epoxy resin circuit boards and upholstery, have potential negative impact on environment as well as health. TBBPA and HBCD have been found in human serum samples and may increase the risk of lymphoma and leukemia. Lymphocytes and monocytes are immune cells that protect us from infection and tumor growth in part by the secretion of cytokines such as the pro-inflammatory cytokine interleukin 1 beta (IL-1β). IL-1β is an important regulator of immune responsiveness and tissue growth and repair. Thus, if its levels are dysregulated, loss of proper immune function and increased invasiveness of tumors could ensue. Our previous studies have shown that TBBPA and HBCD interfere with the function of human natural killer (NK) lymphocytes. Based on these facts, this current study examines whether incubations with varying concentrations (0.05-5 µM) of TBBPA and HBCD for 24 h, 48 h and 6 d interfere with the ability of immune cells to secrete IL-1β. Effects of TBBPA and HBCD on IL-1β secretion were detected by enzyme linked immunosorbent assay (ELISA). Results indicate that exposures of NK cells, MD-PBMCs and PBMCs to different concentrations of TBBPA and HBCD ranging from (0.05-5 µM) for 24 h, 48 h and 6 d influence the ability of immune cells to secrete IL-1β. TBBPA altered secretion of IL-1β from all types of cell preparation in some concentration. Certain concentrations of HBCD caused increases in IL-1β secretion after all lengths of exposures in all cell preparations. Thus, exposure to these compounds may potentially disrupt the immune regulation mediated by IL-1β. Examination of the signaling pathway(s) responsible for the elevated secretion of IL-1β after HBCD exposure were carried out in MD-PBMCs. Pathways examined were IL-1β processing (Caspase-1), mitogen-activated protein kinases (MAPKs), and nuclear factor kappa B (NFκB). Results revealed that MAPK pathways (p44/42 and p38) appear to be the targets of HBCD that lead to increased IL-1β secretion from immune cells.^
Sharif Md Anisuzzaman,
"Tetrabromobisphenol a and hexabromocyclododecane alter the secretion of interleukin 1 beta (IL-1beta) from human immune cells"
ETD Collection for Tennessee State University.