Tacrolimus alleviates acute liver graft rejection by inhibiting glucocorticoid-induced tumor necrosis factor-related protein ligand in rats / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the mechanism underlying the inhibitory effect of tacrolimus (FK506) against acute liver graft rejection.</p><p><b>METHODS</b>Rat models of orthotopic liver transplantation were divided into 3 groups, namely the tolerance group with Brown Norway (BN) rats as the donors and Lewis rats as the recipients, rejection group with Lewis rats as donors and BN rats as recipients, and FK506 group with the same donor-recipient pair as in the rejection group and FK506 treatment. The recipients were sacrificed 7 days after the transplantation, and the hepatic histology, cytokine levels, and glucocorticoid-induced tumor necrosis factor-related protein ligand (GITRL) expression in the liver and Kupffer cells were observed and detected.</p><p><b>RESULTS</b>Compared with the tolerance group, the rejection group showed increased GITRL expressions in the liver and Kupffer cells (P<0.05), which was significantly lowered by FK506 treatment (P<0.05). Acute liver graft rejection caused significantly elevated interferon-γ (IFN-γ) levels and decreased interleukin-10 (IL-10) levels in the plasma and Kupffer cells (P<0.05), and these changes were obviously attenuated by FK506 treatment (P<0.05).</p><p><b>CONCLUSION</b>The effect of FK506 in suppressing acute liver graft rejection is probably associated with down-regulated GITRL expression in the liver and Kupffer cells.</p>