Autophagic activation of IRF-1 aggravates hepatic ischemia-reperfusion injury via JNK signaling.

Increasing evidence has accrued indicating that autophagy is associated with hepatic ischemia-reperfusion injury (IRI). This report demonstrates that interferon regulatory factor-1 (IRF-1) was upregulated in response to hepatic IRI and was associated with autophagic activation. As a result of these processes, there is an aggravation of liver damage, effects that can be offset by IRF-1 depletion. In addition, these effects of IRF-1 are associated with JNK pathway activation followed by increases in Beclin1 protein levels. This JNK-induced autophagic cell death then leads to cell failure, and plays an important role in liver function damage. We conclude that IRF-1 activates autophagy through JNK-mediated autophagy. Accordingly, these findings indicating that the IRF-1/JNK pathway activates autophagy to exacerbate liver IRI in this mouse model may provide new insights into novel protective therapies for hepatic IRI.