Molecular mediators of liver ischemia and reperfusion injury: a brief review

Abstract

Ischemia and reperfusion injury is a dynamic process that involves multiple organ systems in various clinical states including transplantation, trauma, and surgery. Research into this field has identified key molecular and signaling players that mediate, modulate, or augment cellular, tissue, and organ injury during this disease process. Further elucidation of the molecular mechanisms should provide the rationale to identify much-needed novel therapeutic options to prevent or ameliorate organ damage due to ischemia and reperfusion in clinics.

Figure 1

Ischemia-reperfusion injury in the liver involves the initial production of oxygen-free radicals and damage-associated molecules with the subsequent involvement of various molecular and cellular cascades, including the Toll-like receptor 4 system, heme oxygenase system, and leukocyte-sinusoidal endothelial cross-talk interactions. Activation of downstream mediators enables the balance between pro-inflammatory and anti-inflammatory responses and the transition from innate to adaptive immune response.

Figure 2

In liver ischemia reperfusion injury, the Toll-like receptor 4 (TLR4) system is activated by endogenous and exogenous ligands leading to downstream signal transduction and upregulation of chemokines/cytokines, interferon (IFN)-inducible genes, and costimulatory molecules. These pathways result in full engagement of the innate immune response, transitions to the adaptive immune response, and ultimate hepatocellular damage.