At the mechanistic level, DON has been shown in vitro and in vivo to activate mitogen-activated protein kinases (MAPKs), including p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) in macrophages and monocytes (Islam et al. 2006; Shifrin and Anderson, 1999; Zhou et al., 2003a) . These MAPKs mediate upregulation of proinflammatory cytokine and chemokine expression as well as apoptosis (Chung et al., 2003; Islam et al., 2006; Moon and Pestka, 2002) . Notably, DON concentration dependently induces competing survival (ERK/AKT/p90Rsk/Bad) and apoptotic (p38/p53/Bax/ mitochondria/caspase-3) pathways in the macrophage (Zhou et al., 2005a) . Accordingly, MAPK activation is critical to both stimulation and suppression of the innate immune system.