[Ciclosporin down-regulates interferon-gamma gene transcription via its inhibition of nuclear factor kappaB activity after liver transplantation].
OBJECTIVE
To investigate the relation between the activity of nuclear factor kappaB (NF-kappaB) and the expression of interferon (IFN)-gamma gene transcription with or without ciclosporin treatment after liver transplantation.


METHODS
Orthotopic liver transplantation was performed in this study. Group I: syngeneic control (Wistar-to-Wistar); Group II: acute rejection (SD-to-Wistar); Group III: acute rejection treated with ciclosporin by intramuscular route (SD-to-Wistar + ciclosporin). Electrophoretic mobility shift assay and reverse transcriptase polymerase chain reaction were used to analyze NF-kappaB activity of splenocytes and IFN-gamma gene transcription expression of grafted liver with or without ciclosporin treatment after liver transplantation. Histopathological examination was also used in this study.


RESULTS
Low NF-kappaB activity was only detected at day 5 and day 7 in Wistar-to-Wistar group after transplantation, meanwhile low IFN-gamma mRNA expression was detected at any time in this group. In contrast, high NF-kappaB activity was detected in SD-to-Wistar group and high level IFN-gammamRNA expression was detected at all time points in this group. The activity of NF-kappaB and IFN-gammamRNA expression were significantly inhibited in SD-to-Wistar + ciclosporin group which was significantly lower than that of SD-to-Wistar group (P < 0.001). A good correlation was found between activity of NF-kappaB and IFN-gamma mRNA expression in this study (r=0.815, P <0.01).


CONCLUSIONS
The change of expression IFN-gamma mRNA is at least partially due to the activity change of NF-kappaB after orthotopic liver transplantation. CsA down-regulates NF-kappaB activity and further inhibit IFN-gamma gene transcription.
Jia
Chang-Ku
CK
Department of Hepatobiliary Pancreatic Surgery, the First Affiliated Hospital, Medical School of Zhejiang University, Hangzhou 310003, China.
Zheng
Shu-Sen
SS
Shi
Shao-Hua
SH
Zhang
Ai-Bin
AB
Xie
Hai-Yang
HY
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D007371:Interferon-gamma / Q000187:drug effects / Q000235:genetics*; D016031:Liver Transplantation; D008168:Lung / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014184:Transplantation, Homologous
D016328:NF-kappa B; D012333:RNA, Messenger; D007371:Interferon-gamma; D016572:Cyclosporine