Low dose LPS activates ATF2 through IRAK-1 and Tollip-mediated production of mitochondria ROS. In the meantime, low dose LPS suppresses PI3K, IRAK-M, and other related negative regulators. As a consequence, low dose LPS induces mild, prolonged, and skewed expression of pro-inflammatory mediators. In contrast, high dose LPS potently activated NFκB pathway, as well as the PI3K pathway, and causes robust yet transient expression of pro- and anti-inflammatory mediators.