Fig. 1.

Proposed mechanism of LPS/RAN-induced liver injury. RAN augments TNFα production after LPS treatment in a post-transcriptional manner by enhancing p38 activation. The increase in TNFα protein occurs through the p38-dependent activation of TACE. The prolongation of LPS-induced TNF-α production by RAN seems to be crucial for liver injury. TNFα leads to coagulation system activation and PAI-1 production, both of which cause hepatic fibrin deposition. PAI-1 might also contribute to the activation of hepatic PMNs accumulated after LPS exposure. The hypoxia resulting from hepatic fibrin deposition and perhaps other factors could act synergistically with toxic proteases released from activated PMNs to kill hepatocytes. PMN proteases are also involved in enhancing PAI-1 production and fibrin deposition. HPC, hepatic parenchymal cell; STC, hepatic stellate cell; Trans-factor(s), transcription factor(s).