Reactive oxygen species in TNFalpha-induced signaling and cell death.

TNFalpha is a pleotropic cytokine that initiates many downstream signaling pathways, including NF-kappaB activation, MAP kinase activation and the induction of both apoptosis and necrosis. TNFalpha has shown to lead to reactive oxygen species generation through activation of NADPH oxidase, through mitochondrial pathways, or other enzymes. As discussed, ROS play a role in potentiation or inhibition of many of these signaling pathways. We particularly discuss the role of sustained JNK activation potentiated by ROS, which generally is supportive of apoptosis and "necrotic cell death" through various mechanisms, while ROS could have inhibitory or stimulatory roles in NF-kappaB signaling.