Inflammasome activation involved in early inflammation reaction after liver transplantation

Abstract Liver transplantation has emerged as a vital therapy for end-stage liver diseases. Acute −phase inflammation play an important role in liver graft injury.Recent studies have revealed that inflammasome are responsible for initiating inflammation in early stage of acute organ rejection in liver transplantation, however the underlying mechanism remains unclear. Here we explored to block inflammasome activation to see whether it can alleviate early inflammation reaction during rejection of allgrafts in a rat model and gain further insights into the mechanism of inhibiting inflammation in allografts. By using Ac-YVAD-CMK, a highly selective caspase-1 inhibitor, to inhibit inflammation reaction involved in allograft rejection in a rat model. Our results showed that the rejection activity index (RAI) of Ac-YVAD-CMK-treated allografts is significantly diminished in similar magnitude to that of isografts. Compared with isografts, the expression of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and IL-1β in allograft group increased significantly with the development of rejection, exhibiting apparent correlation. Expression of IFN-γ mRNA in untreated allografts was maximal on day 3 while in Ac-YVAD-CMK-treated allografts and isografts, IFN-γ mRNA levels remained low over the duration of the time course. ELISA results revealed serum elevation of IL-1β by day 7 after othotopic liver transplantation (OLT) in comparison with isografts. There were no statistically significant differences between isografts and Ac-YVAD-CMK-treated allografts. For the first time, our data reveal that inhibition of the inflammasome activation pathway attenuates inflammation reaction of hepatic transplant rejection.