PIM Kinase Control in Inflammasome Signaling in Macrophage Survival

Abstract

The tumor microenvironment consists of a variety of different cell types that contribute to helping maintain tumor cell survival in a harsh and ever-changing environment. The goal of this study was to determine how PIM kinases impact cellular ROS production and survival in tumor associated macrophages, and how the NLRP3 inflammasome is affected by PIM activity and changes in cellular ROS. We found that PIM inhibition significantly increases intracellular ROS in macrophages in a concentration- and time-dependent basis. Through western blotting and RT-PCR, we utilized protocols to activate the inflammasome and show how different treatment techniques, such as the inhibition of ROS, can modulate expression and activation of caspase - 1. We primarily demonstrate a direct relationship between the inhibition of PIM kinase and increased cellular ROS. The inhibition of PIM increases ROS and kills macrophages through a caspase – 1 dependent manner. This data helps to improve our current understanding of PIM kinase signaling in macrophages and can be used as a steppingstone to direct future studies investigating the potential role of PIM kinase inhibitors as a novel therapeutic approach to combat pro-tumorigenic effects of the immune system to improve cancer treatment.