CsA downregulates IFN-gamma gene transcription after liver transplantation by inhibiting NF-kappa B activity / 中华医学杂志(英文版)

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the relationship between NF-kappa B activity and IFN-gamma gene expression, as well as the histopathological changes following liver transplants, both with and without cyclosporin A (CsA) treatment.</p><p><b>METHODS</b>Sixty male Wistar and Thirty male SD rats were subjected to orthotopic liver transplants. Fourty-five of the Wistar rats were used as recipients, and were divided into 3 groups group I, syngeneic control (Wistar-to-Wistar); group II, acute rejection (SD-to-Wistar); and group III acute rejection treated with cyclosporin A by intramuscular injection (SD-to-Wistar + CSA). After the liver transplants, electrophoretic gel mobility shift assay was used to analyze NF-kappa B activity in the splenocytes of recipient rats, and RT-PCR was used to measure IFN-gamma gene expression in grafted liver specimens. In addition, histopathological examinations were performed to assess the severity of acute liver rejection.</p><p><b>RESULTS</b>In group I, low levels of NF-kappa B activity were only detectable on day 5 and 7 post-transplant, and only weak IFN-gamma mRNA expression was observed at all time points. By contrast, both high NF-kappa B activity and high expression levels of IFN-gamma mRNA were detected at all time points in group II. In group III, NF-kappa B activity and IFN-gamma mRNA expression were significantly inhibited, as compared to group II (P < 0.05). A good correlation was found between NF-kappa B activity and IFN-gamma mRNA expression (r = 0.815). In addition, NF-kappa B activity and IFN-gamma mRNA expression mirrored histopathological changes in all three experimental groups.</p><p><b>CONCLUSIONS</b>Changes in IFN-gamma mRNA expression levels after liver transplantation are at least partially due to changes in levels of NF-kappa B activity. CsA appears to downregulate NF-kappa B activity, thus inhibiting IFN-gamma gene transcription. Blocking the NF-kappa B mediated transcription pathway may be of benefit in preventing liver transplant rejection.</p>