Molecular mechanisms of liver ischemia reperfusion injury: Insights from transgenic knockout models

Figure 2 Cytokine and downstream signalling pathways in liver ischaemia reperfusion injury. Following liver ischaemia reperfusion, there is activation of tumor necrosis factor-α (TNF-α) is by chemokine (CXCL) 10, interferon regulatory factor (IRF) and toll-like receptor (TLR) 4 in parallel. TNF-α activates downstream hepatocyte/sinusoidal endothelial cells (SEC) nuclear factor κβ (NFκβ) and CD4+ T cells separately which activate c-Jun N-terminal protein kinase-2 (JNK-2) and signal transducer activator of transcription-4 (STAT4), respectively leading to increased cell injury. A parallel pathway of cell injury occurs where TLR4 activation stimulates interferon (IFN)-β and IFN-γ expression, which acting through their receptor IFN receptor subtype (AR) activate interferon regulatory element (IRE)-1 which in turn activate CD4+ T cells. CXCR: Chemokine receptor.