Over-expression of Toll-like receptors and their ligands in small-for-size graft

Hepatol Res. 2010 Apr;40(4):318-29. doi: 10.1111/j.1872-034X.2009.00603.x. Epub 2010 Jan 11.

Abstract

Aim: Toll-like receptors (TLRs) participate in several physiological and pathological processes of transplantation, including inflammation and allograft rejection, but the expression of TLRs and their ligands remains undetermined in small-for-size graft transplantation.

Methods: A non-arterialized partial liver transplantation model was used. The expression of TLR2 and TLR4 mRNA and protein, CD14 and Myeloid Differentiation-2 (MD-2) mRNA, as well as TLR2 and TLR4 exogenous ligands (endotoxin) and endogenous ligands [heat shock protein (HSP) 60 and 70] were assessed. The signaling pathways induced by TLR2 and TLR4 were also assessed.

Results: In small-for-size liver graft, the expression of mRNA and protein of TLR2 and TLR4, CD14 and MD-2 mRNA, as well as endogenous ligands of TLR2 and TLR4 such as HSP60 and HSP70 was quickly and significantly increased after reperfusion, and reached a peak at 3 h after reperfusion. The levels of exogenous ligands (endotoxin) were increased and reached a peak at 6 h after reperfusion. The appearance of TLR2 and TLR4 mRNA was accompanied by increased HSP 60 and 70 mRNA within 24 h after reperfusion. In the small-for-size group, the peak levels of TLRs and their endogenous ligands appeared earlier than those in the full size group; the peak levels of TLRs and their endogenous and exogenous ligands were higher than those in the full size group.

Conclusion: TLR2 and TLR4, as well as their endogenous and exogenous ligands were activated in small-for-size liver graft transplantation.