NEMOΔhepa mice are sensitive to low doses of TRAIL-mediated liver injury. 25 mg/kg of flagged TRAIL was administered i.v. (A) ALT serum levels were significantly elevated in NEMOΔhepa mice after TRAIL. (B–D) H&E staining (B), TUNEL assay (C), and caspase 3 activity (D) showed TRAIL-mediated liver damage and apoptosis in NEMOΔhepa mice. (E) Western blot analysis showed JNK phosphorylation. JNK1 and GAPDH were used as loading controls. (F) RT-PCR analysis of TNF mRNA and IHC showed higher expression in NEMOΔhepa mice. (G) mRNA analysis and IHC evidenced strong DR5 expression in NEMOΔhepa livers compared with NEMOf/f. Bars, 50 µm. All data are representative of three independent experiments. n = 4. **, P < 0.01; ***, P < 0.001 (NEMOf/f vs. NEMOΔhepa). §§, P < 0.01; §§§, P < 0.001 (NEMOΔhepa vs. TRAIL/NEMOΔhepa). Error bars represent SD.
