The expression profiles and significance of IL-33 and its receptor ST2 in a murine model of D-GalN/LPS -induced acute liver failure

Abstract

Abstract: Objective To investigate the expression profiles and implication of IL-33 and its receptor ST2 in a murine model of acute liver failure (ALF) induced by D-GalN/LPS.Methods The ALF murine model was set up by intraperitoneal injection of D-GalN (900 mg/kg)/LPS(10 ug/kg), and confirmed by histopathology and biochemistry. Dynamic expression profiles of IL-33 and its receptor ST2 in ALF murine model were investigated by quantitative polymerase chain reaction (q-PCR), western-blot, enzyme-linked immune-sorbent assay (ELISA) and immunohistochemistry at different time points, respectively. Results The murine model of ALF was successfully established by intraperitoneal injection of D-GalN (900 mg/kg)/LPS(10 ug/kg). The mRNA level of intra-hepatic IL-33 continuously increased with the progression of ALF, and reached the peak at 7 h after D-GalN/LPS challenge. Compared to baseline, intra-hepatic ST2L protein level was markedly up-regulated at 3 h, which was before the occurrence of obvious hepatocytes damage. However, it declined later on and fall to the lowest at 7 h. In addition, it was observed that IL-33 protein level in serum was elevated sustainedly over time and reached the highest level at 7 h, which was consistent with its dynamic mRNA changes. In contrast, the serum level of sST2 had no significant differences between 0 h and 3 h at the early stage of liver damage, but showed an obvious rise to climax at 5 h in the medium-term of liver damage, and then was followed by a drastic decline. The immunohistochemistry results confirmed that intra-hepatic IL-33 was mainly located in the nucleus of endothelial cells and sinusoidal cells in ALF mouse liver.Conclusion The dynamic changes of IL-33 and its receptor ST2 in ALF mice are closely linked with the progression of acute liver failure, suggesting that IL-33/ST2 axis is indeed involved in the process of ALF. This might provide a novel potential target for ALF treatment.

Key words: IL-33, ST2L, sST2, ALF, Dynamic expression

JIANG Shao-wen, LIN Lan-yi, XIANG Xiao-gang, LU Jie, WANG Fan, MO Rui-dong, LIU Yu-han, CAI Wei, WANG Hui, XIE Qing. The expression profiles and significance of IL-33 and its receptor ST2 in a murine model of D-GalN/LPS -induced acute liver failure[J]. Chinese Hepatolgy, 2016, 21(4): 267-272.

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