The effect of TBBPA on MAP3Ks in human natural killer cells

Abstract

Natural killer (NK) cells are part of the innate immune system. Upon encountering a tumor cell, virally‐infected cell, or antibody‐coated cell, the NK cell releases cytotoxic granules which lead to the lysis of the target cell. Tetrabromobisphenol A (TBBPA) is an organic brominated flame retardant (BFR) known to have harmful effects on the environment. It is utilized as a heat resistant chemical in various industrial and commercial applications in order to retard the burning of textiles, buildings, plastics, among other things. Significant levels of TBBPA have been found in human serum, human milk and adipose tissue. Human exposure can result from the inhalation of polluted air and/or the ingestion of contaminated food. A previous study demonstrated that a twenty‐four hour exposure of NK cells to 5μM of TBBPA resulted in a >;95% decrease in cytotoxic function and exposure to 2.5 μM of TBBPA resulted in a 76% decrease in lytic function. TBBPA also caused a decrease in NK cell binding capacity by 70% at 5 μM. We have shown that exposureto this chemical leads to the activation of specific Mitogen‐Activated‐Protein‐Kinases(MAPKs) and MAPK‐Kinases (MAP2Ks) in human NK cells. The objective of this study is to examine whether there also exists a TBBPA‐induced activation of MAP3Ks, the upstream regulator MAP2Ks. Our results show significant activating phosphorylations of MAP3Ks after exposure of human NK cells to TBBPA.