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

Yoshihito Takahashi, 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, Noriko Murase

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

The role of NF-κB, the rapid-response 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 AdIκB. In uninfected control livers, NF-κB 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 NF-κB activation associated with an increase of mRNA for TNF-α, IL-1β, and IL-10. AdEGFP transfection resulted in similar outcomes. Interestingly, AdIκB-transfected liver grafts suffered more severe I/R injury (AST <9,000 IU/l). Transfected IκB 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 NF-κB activation at 12-48 h and increased apoptosis. Thus inhibition of the second wave of NF-κB activation in IκB-transfected livers resulted in an increase of liver injury, suggesting that NF-κB may have a dual role during liver I/R injury.

Original languageEnglish
Pages (from-to)G1175-G1184
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume283
Issue number5 46-5
Publication statusPublished - Nov 1 2002
Externally publishedYes

Keywords

  • Adenoviral vector
  • IκB
  • Liver transplantation
  • Preservation injuries

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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  • Cite this

    Takahashi, Y., Ganster, R. W., Gambotto, A., Shao, L., Kaizu, T., Wu, T., Yagnik, G. P., Nakao, A., Tsoulfas, G., Ishikawa, T., Okuda, T., Geller, D. A., & Murase, N. (2002). Role of NF-κB on liver cold ischemia-reperfusion injury. American Journal of Physiology - Gastrointestinal and Liver Physiology, 283(5 46-5), G1175-G1184.