Ciclosporin down-regulates interferon-gamma gene transcription via its inhibition of nuclear factor kappaB activity after liver transplantation / 中华外科杂志

ABSTRACT

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>