TREM-1 inhibition of Kupffer cells alleviates inflammation, oxidation, and apoptosis induced in rat liver by heat stroke

Abstract

To investigate the effect and probable mechanism of triggering receptor expressed on myeloid cells-1 (TREM-1) inhibition of hyperactive Kupffer cells (KCs) on acute liver injury caused by severe heat stroke (HS). A total of 32 rats were randomized into the LP17, GdCl3, control (CON), and heat stroke (HS) groups. Serum ALT and AST activities in each group were assessed. Additionally, liver tissues were obtained to examine cellular structure, determine superoxide dismutase (SOD) concentrations, analyze apoptosis, and determine the expression levels of TREM-1, TREM-2, DAP12, TNF-α, and IL-6 in KCs, as well as Bcl-2, Bax, CleveadCaspase3, and Clevead-Caspase9 in liver. Results of the study showed that compared to the CON group, the HS group had higher serum AST and ALT levels, with more serious pathological changes. Hepatocyte apoptosis and lysosome formation in KCs increased when heatstroke occurred, while SOD concentrations decreased. Moreover, expression levels of TREM-1, DAP12, TNF-α, IL-6, Bax, Clevead-Caspase3, and Clevead-Caspase9 increased in the HS group, while TREM-2 and Bcl-2 expression levels decreased. Pretreatment with LP17 and GdCl3 significantly ameliorated the aforementioned indicators, relieving acute liver injury caused by heat stroke. The results of this study showed that Inhibiting TREM-1 of KCs improved severe HS-induced liver injury, which involved an underlying mechanism of regulating the imbalance of expressions in the TREMs/DAP12 pathway. Thus, inhibiting KC activities improved antioxidant consumption and alleviated apoptosisrelated protein overexpression, thereby reducing HS-induced hepatocyte apoptosis.