Gene deletion of NF-κB p50 does not alter the hepatic inflammatory response to ischemia/reperfusion

Background/Aims: Nuclear factor κB (NF-κB) is a primary regulator of gene expression and is activated during hepatic ischemia/reperfusion injury. The objective of the present study was to determine whether activation of NF-κB is causally related to the induction of the acute inflammatory response induced by hepatic ischemia/reperfusion. Methods: Wild-type (p50+/+) and NF-κB p50-deficient (p50−/−) mice underwent hepatic ischemia/reperfusion. NF-κB activation was determined by electrophoretic mobility shift assay. Hepatic neutrophil accumulation was measured by liver myeloperoxidase content. Hepatocellular injury was assessed by serum level of alanine aminotransferase and liver histology. Results: In p50+/+ mice, ischemia/reperfusion induced marked activation of NF-κB consisting of p50/p65 heterodimers. In contrast, NF-κB activation in livers from p50−/− mice was abrogated, but p65 was observed in nuclear extracts. Despite amelioration of NF-κB activation there was no significant difference between p50+/+ and p50−/− mice in expression of TNFα and MIP-2, liver accumulation of neutrophils or hepatocellular injury. Conclusions: Gene deletion of NF-κB p50 does not alter the hepatic inflammatory response to ischemia/reperfusion. Despite abrogation of DNA-binding by the NF-κB p50/p65 complex, p65 was still observed in nuclear extracts suggesting that there may be functional redundancy amongst members of the Rel protein family in order to preserve the inflammatory response.