TLR5 silencing reduced hyperammonaemia-induced liver injury by inhibiting oxidative stress and inflammation responses via inactivating NF-κB and MAPK signals

Background Liver injury is a serious threat for human health and life. Toll-like receptor 5 (TLR5) has reported to be a vital mediator in flagellin or tetrachloride (CCl4)-induced liver injury. However, the roles and etiology of TLR5 in hyperammonaemia (HA)-induced liver injury are poor defined. Methods HA rats were generated by intragastric administration using ammonium chloride solution. Liver status was assessed by haematoxylin and eosin (H&E) staining and measuring serum levels of liver injury markers. Immunohistochemistry (IHC) assay was used to visualize protein expression in tissues. Apoptotic index in tissues was determined by TUNEL assay. RT-qPCR assay was employed to test mRNA expression. Oxidative stress responses was assessed by detecting levels of reactive oxygen species (ROS) and related indicators. NF-κB activity was examined by TransAM NF-κB colorimetric kit. Results TLR5 was highly expressed in liver tissues of HA rats. TLR5 knockdown ameliorated HA-induced liver injury by inhibiting liver cell apoptosis. TLR5 depletion inhibited HA-induced pro-inflammatory cytokine expression in liver tissues, but had no effect on the infiltration of T and macrophage cells into liver tissues. TLR5 silencing impaired HA-induced oxidative stress responses in hepatocytes, but not in hepatic stellate cells (HSCs). TLR5 downregulation inhibited HA-induced activation on TLR5/NF-κB and TLR5/MAPK signaling pathways. Conclusion TLR5 silencing reduced HA-induced liver injury by inhibiting hepatocyte apoptosis, oxidative stress and inflammation responses via inactivating NF-κB and MAPK signals, deepening our understanding on the molecular mechanism of HA-induced liver injury and providing a potential therapeutic target for alleviating liver injury.