FIGURE 4.

Effect of decreased Sab expression on GalN/TNF-α-induced hepatotoxicity in vivo and initial TNF receptor signaling in vivo and in PMHs. A, serum ALT of shlacZ- or shsab-pretreated mice at 6 h following TNF-α treatment. Error bars represent S.D. rmTNF-α, recombinant mouse TNF-α. *, p = 0.008 versus shlacZ group (Student's t test; n = 4 per group). B, representative histology of hematoxylin/eosin staining of mouse liver tissue. Scale bars = 100 μm. C and D, effect of Sab knockdown on upstream TNF receptor signaling in vivo and in PMHs. Mice were injected with adenoviral shlacZ or adenoviral shsab as described under “Experimental Procedures.” C, 7 days after adenoviral injection, mice were injected with GalN/TNF-α intraperitoneally, and livers were removed and fractionated. Immunoblotting of liver cytoplasm was performed at the indicated times after GalN/TNF-α treatment in vivo. D, hepatocytes from adenovirus-treated mice were cultured and incubated with TNF-α alone for the indicated times. Immunoblotting of PMH extracts was performed using antisera against p-JNK, p-IκBα, IκBα, and GAPDH (loading control). Data are representative of three experiments.