Abstract: OBJECTIVE: To explore the effect of TAK1 knockout in CD11c⁺ cells on concanavalin A (Con A)-induced immunological liver injury. METHODS: C57BL/6 mice with TAK1 knockout in CD11c⁺ cells were injected intravenously with normal saline or Con A (12 mg/kg) as NS+ and Con A (12 mg/kg)+ knockout groups,respectively. Normal C57BL/6 mice were injected intravenously with normal saline or Con A (12 mg/kg) as NS+ and Con A (12 mg/kg)+ control groups,respectively. After 6 hours,serum was collected to detect the levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST) and lactic dehydrogenase (LDH). Organ coefficients of liver,kidney,thymus and other organs were detected. Histopathological observations and scores were performed. Serum was collected to detect the expression of tumor necrosis factor-α (TNF-α),interferon-γ (IFN-γ) and interleukins (IL-4/5/6 and IL-12). The levels of TNF-α and IFN-γ in liver were detected. RESULTS: Compared with NS+ control group,levels of ALT and LDH were significantly increased in Con A+ control group (P < 0.05). Con A+ control group showed severer pathological liver injury and higher pathological score (P < 0.05). The levels of TNF-α,IFN-γ,IL-4,IL-5,IL-6 in serum and TNF-α and IFN-γ in liver were significantly increased (P < 0.05). Compared with NS+ control group,the level of TNF-α in liver in NS+ knockout group was significantly decreased (P < 0.05). Compared with Con A+ control group,levels of ALT,AST and LDH were significantly increased in Con A+ knockout group (P < 0.05). Con A+ knockout group showed severer pathological liver injury and higher pathological score. The levels of TNF-α,IL-4 and IL-6 in serum and IFN-γ in liver were significantly increased (P < 0.05). CONCLUSION: Knockout of TAK1 in CD11c⁺ cells was not related to liver injury but aggravated concanavalin A-induced immunological liver injury.

Key words: CD11c⁺cell, concanavalin A, immunological liver injury, TGF β-activated kinase 1