Critical Role of Interferon Regulatory Factor-1 in Murine Liver Transplant Ischemia Reperfusion Injury

Abstract

Interferon regulatory factor-1 (IRF-1) is a transcription factor that regulates gene expression during immunity. We hypothesized that IRF-1 plays a pivotal role in liver transplant (

A Critical Role for IFN Regulatory Factor 1 in NKT Cell-Mediated Liver Injury Induced by α-Galactosylceramide

“…Importantly, it was the specific presence of IRF-1 in the donor liver graft, but not the recipient host, that accounted for the liver damage (27,28). Moreover, overexpression of IRF-1 exacerbated routine preservation injury (27,28). Based on our present and previous observations and known roles for NKT cells in liver I/R injury, it FIGURE 7.…”

“…Recent work in our laboratory suggested that IRF-1 contributes to liver damage induced by warm hepatic I/R injury (26,27). Furthermore, we have also shown that IRF-1 plays a critical role in liver transplant preservation injury (27,28). IRF-1 expression itself can be regulated by many factors, among which IFN-g is the strongest IRF-1 inducer known so far (22).…”

“…We have previously shown that IRF-1 expression is upregulated in the liver following both warm and cold I/R injury, and increased IRF-1 expression contributes to the hepatic damage whereas the IRF-1 knockout mice were protected from the injury (26,27). Importantly, it was the specific presence of IRF-1 in the donor liver graft, but not the recipient host, that accounted for the liver damage (27,28). Moreover, overexpression of IRF-1 exacerbated routine preservation injury (27,28).…”

Interferon Regulatory Factor Signalings in Cardiometabolic Diseases

“…81 The detrimental effect of IRF1 overexpression on liver damage has been confirmed in an orthotopic liver transplantation mouse model. 173,174 Rats that were pretreated with AdIRF1 exhibited increased susceptibility to liver damage, along with enhanced early apoptosis and immune responses in the transplanted grafts 173 ; however, IRF1 deficiency in the mouse liver grafts dramatically reduced liver injury and improved the survival rate of these mice. 174 The mechanisms underlying the deteriorated effects of IRF1 on hepatic I/R injury-induced liver damage might include the alteration of the inflammatory and apoptotic responses by mediating MAPK and TLR signaling.…”

“…173,174 Rats that were pretreated with AdIRF1 exhibited increased susceptibility to liver damage, along with enhanced early apoptosis and immune responses in the transplanted grafts 173 ; however, IRF1 deficiency in the mouse liver grafts dramatically reduced liver injury and improved the survival rate of these mice. 174 The mechanisms underlying the deteriorated effects of IRF1 on hepatic I/R injury-induced liver damage might include the alteration of the inflammatory and apoptotic responses by mediating MAPK and TLR signaling. 81,173 Interferon Regulatory Factor 2 Given that IRF2 suppresses the transcriptional activation of IRF1 in the immune system, 175 the upregulation of IRF2 might provide a possible strategy to prevent the IRF1-elicited exacerbation of I/R injury.…”