Liver injury and STAT1 and SOCS1 activation are attenuated, but STAT3 and SOCS3 activation are enhanced and prolonged in Con A–induced hepatitis in STAT1^–/– mice. (a) Mice were injected with 22 μg/g of Con A. At various time points, serum ALT levels were measured. Values are shown as means ± SEM from four mice at each time point. (b) Photomicrographs of representative mouse livers from 9-hour Con A–treated wild-type and STAT1^–/– mice with H&E staining are shown (original magnification ×200 and ×400). White arrows indicate massive necrosis observed in the liver. (c) Wild-type control and STAT1^–/– mice were injected with Con A (22 μg/g). At various time points after injection, serum was collected, and circulating IFN-γ levels were measured by ELISA. Values are shown as means ± SEM from three mice at each time point. (d) Total liver protein extracts and RNA from Con A–treated STAT1^+/+ and STAT1^–/– mice were analyzed by Western blotting and RT-PCR (indicated by asterisks), respectively, using Ab’s and primers as indicated. Induction of pSTAT1, pSTAT3, IRF-1, Bcl-X_L, SOCS1, and SOCS3 was quantified by PhosphorImager analysis (left panel), as described in Methods. The values are shown as means ± SEM from four independent experiments at each time point. *P < 0.001, ^#P < 0.01 vs. corresponding Con A–treated wild-type control groups at the same time points.