Role of NF- B on liver cold ischemia-reperfusion injury

Takahashi, Yoshihito, Raymond W. Ganster, Andrea Gambotto, Lifang Shao, Takashi Kaizu, Tong Wu, Gautam P. Yagnik, Atsunori Nakao, George Tsoulfas, Takashi Ishikawa, Toyokazu Okuda, David A. Geller, and Noriko Murase. Role of NFB on liver cold ischemiareperfusion injury. Am J Physiol Gastrointest Liver Physiol 283: G1175–G1184, 2002. First published July 17, 2002; 10.1152/ajpgi.00515.2001.—The role of NFB, the rapidresponse transcription factor for multiple genes, in cold ischemia-reperfusion (I/R) injury was examined after syngeneic transplantation of liver grafts. Lewis rat recipients were killed 1–48 h after reperfusion of three different liver grafts: 1) uninfected control, 2) infected ex vivo with control adenoviral vector (AdEGFP), and 3) infected ex vivo with AdI B. In uninfected control livers, NFB was activated biphasically at 1–3 and 12 h after reperfusion with aspartate transaminase (AST) levels of 4,244 691 IU/l. The first peak of NFB activation associated with an increase of mRNA for TNF, IL-1 , and IL-10. AdEGFP transfection resulted in similar outcomes. Interestingly, AdI B-transfected liver grafts suffered more severe I/R injury (AST 9,000 IU/l). Transfected I B was detected in transplanted livers as early as 6 h, and this correlated with the abrogation of the second, but not the first, peak of NFB activation at 12–48 h and increased apoptosis. Thus inhibition of the second wave of NFB activation in I B-transfected livers resulted in an increase of liver injury, suggesting that NFB may have a dual role during liver I/R injury.