Ischemiareperfusion liver injury

Ischemia/reperfusion injury of the liver occurs in procedures such as partial hepa-tectomy and liver transplantation. Kupffer cells play a prominent role in ischemia/ reperfusion injury of the liver (as outlined in Fig. 4). After activation, Kupffer cells produce proinflammatory cytokines that damage hepatic endothelial cells, hepa-tocytes and neutrophils leading to the recruitment of T lymphocytes and hepatic inflammation. After liver transplantation, not only LPS, but also endogenous TLR ligands such as hsp60 and hsp70 are strongly elevated in serum and liver [50, 51]. In TLR4-deficient mice and mice deficient in IRF-3, ischemia/reperfusion-induced liver inflammation and hepatocellular damage is almost completely prevented, whereas ischemia/reperfusion liver injury was unchanged in MyD88-deficient mice [52]. These findings indicate that ischemic-reperfusion induces liver injury through TLR4-mediated IRF-3-dependent, but MyD88-independent signaling pathway [26].

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