Prevention of hepatic ischemia-reperfusion injury by gene transfer of IкB antisense and its application to liver transplantation

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NFкB is a transcriptional factor which plays a major role in production of inflammatory cytokines and regulation of apoptosis. However, it is still unclear whether up-regulation of NFкB has a cytoprotective effect or not in hepatic ischemia-reperfusion injury. We already constructed a recombinant adenovirus vector expressing a truncated form of the inhibition protein IкB (Adex IкB), and demonstrated that transfer of Adex IкB inhibited NFкB activation and aggravated hepatic ischemia-reperfusion injury in rats. In the present study, we tried to construct Adex IкB antisense suppressing IкB production and investigated the effect of IкB antisense gene transfer to NFкB activation and ischemia-reperfusion injury. In vitro, amount of IкB was not decreased in cultured cells infected Adex IкB antisense, although IкB antisense cDNA was detected by RT-PCR. In hepatic ischemia-reperfusion model in rats, administration of Adex IкB antisense did not attenuate hepatic injury compared to the control group