Mechanisms of crosstalk between TNF-induced NF-κB and JNK activation in hepatocytes

摘要: Hepatocyte cell death is a universal feature of inflammatory liver diseases. The observation that mice deficient in the activation nuclear factor-kappaB (NF-kappaB) are not viable because excessive hepatocyte apoptosis induced by tumor necrosis factor (TNF) made it crystal-clear NF-kappaB plays central role protecting hepatocytes against TNF-induced death. Also during TNF-mediated injury, was shown to have an essential anti-apoptotic effect, underscoring therapeutic importance understanding its underlying molecular mechanisms. For long time, ability induce expression variety proteins thought be solely responsible for cytoprotective effects. However, past few years has become clear NF-kappaB-mediated inhibition also involves attenuating c-Jun activating kinase (JNK). Whereas transient JNK upon TNF treatment associated with cellular survival, prolonged contributes Several studies inhibits sustained phase and thus protects cells cytotoxicity. In this review, we will discuss various mechanisms which blunts activation, including induction inhibitory controlling levels reactive oxygen species (ROS). Moreover, effects particularly important physiology, put each these JNK-inhibitory into 'hepatic perspective' discussing their mouse models injury.