Allograft inflammatory factor-1 is up-regulated in warm and cold ischemia-reperfusion injury in rat liver and may be inhibited by FK506.
BACKGROUND
Allograft inflammatory factor-1 (AIF-1) plays an important role in immune response and vasculopathy in allografts. The present study investigated activation of AIF-1 in warm and cold ischemia-reperfusion (IR) injury of rat liver, and the potential inhibitory effect of FK506.


METHODS
We used warm IR injury, orthotopic transplantation, and allograft rejection models in this study. We assessed expression of AIF-1 mRNA and protein, as well as its inducers interferon-γ (IFN-γ) and interleukin-1β (IL-1β). The potential inhibitory effect of FK506 on AIF-1 in a rat macrophage cell line and in these three models was also assessed.


RESULTS
AIF-1 mRNA and protein, as well as its inducers IFN-γ and IL-1β, were significantly increased in the warm IR injury, orthotopic transplantation, and allograft rejection models. Real-time RT-PCR and Western blotting showed that pretreatment with low-dose FK506 partially inhibited AIF-1 activation as well as its inducers (IFN-γ and IL-1β) in these three models. Western blotting showed that IFN-γ and IL-1β activated AIF-1 in a macrophage cell line, but pretreatment with FK506 did not inhibit AIF-1 activation in vitro. Hematoxylin and eosin staining showed that edema and necrosis in the liver, as well as alanine aminotransferase (ALT) in serum, of these three groups was reduced after FK506 pretreatment.


CONCLUSIONS
AIF-1 was activated in warm and cold IR injury, and pretreatment with low-dose FK506 partly inhibited AIF-1 activation and reduced warm and cold IR injury.
Jiang
Weiwei
W
Department of Neonatal Surgery, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing, China.
Kong
Lianbao
L
Wu
Xiaofeng
X
Pu
Liyong
L
Wang
Xuehao
X
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D008297:Male; D008840:Microfilament Proteins; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000378:metabolism*; D016559:Tacrolimus / Q000494:pharmacology*; D015854:Up-Regulation
C100745:Aif1 protein, rat; D002135:Calcium-Binding Proteins; D007166:Immunosuppressive Agents; D008840:Microfilament Proteins; D000410:Alanine Transaminase; D016559:Tacrolimus