Effect of TRAF1 on Phenotypic Changes Of Kupffer Cells In Liver Transplantation Ischemic-Reperfusion

Abstract

Objective: The purpose of this study was to explore the effect of TRAF1 on phenotypic changes of KCs in I/R in liver transplantation. Methods: SD rats were randomly divided into sham group and liver transplantation I/R group. KCs were extracted from rat livers in each group. KCs were transfected by lentivirus of si-TRAF1 or si-HOIP, and induced by lipopolysaccharide (LPS). Flow cytometry was used to detect cell apoptosis. Western blot and RT-PCR were used to detect the protein and mRNA expression levels. Results: Compared with sham group, the expression levels of TRAF1, TNF-α and IL-1β were significantly increased in I/R group (P<0.05). In addition, compared with control group, the expression levels of NF-κB (P65 and p-P65) and M1 phenotype (TNF-α and IL-1β) were notably increased in si-TRAF1 and si-HOIP group (all P<0.05). Furthermore, the levels of linear ubiquitin complex (LUBAC) were markedly increased in LPS-induced KCs in comparison with control group (P<0.05). Moreover, compared with control group, the expression levels of P65, p-P65, TNF-α and IL-1β were notably decreased in si-TRAF1 and si-HOIP group (P<0.05). The expression levels of P65, p-P65, TNF-α and IL-1β were significantly increased in si-TRAF1 and si-HOIP group when compared to control group (P<0.05). Conclusion: TRAF1 was an important negative regulator of liver transplantation I/R by inhibiting the activation of NF-κB in KCs and preventing its M1 phenotype transformation.

DUSP9 alleviates hepatic ischemia/reperfusion injury by restraining both mitogen-activated protein kinase and IKK in an apoptosis signal-regulating kinase 1-dependent manner

“…Among the constituent cells in the liver, it appears that both parenchymal and nonparenchymal cells can guide stress signals, resulting in the progression of hepatic I/R injury [ 7 , 8 ] . As liver-resident macrophages, Kupffer cells show high sensitivity to liver I/R injury and can mediate multiple stress signals contributing to the exacerbation of hepatic impairment according to previous studies [ 9 , 10 ] . Therefore, targeting the transduction of stress signals in Kupffer cells is one of the directions for alleviating liver I/R injury.…”