Acrylamide‐induced apoptosis in macrophages: anti‐apoptotic role of ATF3

Apoptosis is programed cell death characterized by certain cellular changes and regulated by proapoptotic and antiapototic gene products. Acrylamide (ACR) has been known to induce versatile adverse effects including immunotoxic effects. However, little is known regarding the mechanism by which ACR induces apoptosis in macrophages. We examined the role of ATF3 in ACR‐induced apoptosis in macrophages. In this study, ATF3 expression is strongly induced by cellular damage by ACR. ACR decreased dose‐dependently cell viability in macrophages with a pronounced apoptotic effect at its high concentration. We determined the level of ROS and apoptotic proteins in macrophages depleted with ATF3 using small interfering RNA. Using fluorocytometry, treatment of macrophages with ACR resulted in a dose‐dependent increase in ROS production and especially ROS was more increase in ATF3 knockdown cells, suggesting that ROS is regulated by ATF3 in macrophages. Western blot analysis revealed that the levels of Bax and caspase3 were increased in ATF3 knockdown cells, whereas Bcl2 and Bcl‐xl levels were decreased. In addition, staining with both Annexin V and PI showed that ATF3 knockdown cells are more susceptible to apoptosis induced by ACR. Our findings indicate that ATF3 has an anti‐apoptotic role in macrophages by regulating ROS production and apoptotic protein expressions in response to stress‐inducing chemical.