Deletion of IKK2 in hepatocytes does not sensitize these cells to TNF-induced apoptosis but protects from ischemia/reperfusion injury
J. Clin. Invest. Tom Luedde, et al. 115:849 doi:10.1172/JCI23493 [Go to this article.]

Figure 2
Nemo, but not Ikk2, deletion results in apoptotic cell death in the liver upon TNF-α stimulation. (A) Ikk2Δhepa, Ikk2Δ, or NemoΔ mice and their respective control litter mates (Ikk2^f/f or Nemo^f/f) were injected intravenously with 6 μg/kg of recombinant TNF-α or intraperitoneally with LPS (100 μg/kg) and GalN (800 mg/kg) (right top panel). Liver injury was measured by determining ALT levels. Values are mean ± SD for independent animals (n = 6). Single asterisks indicate statistical significance with P < 0.01 versus Nemo^f/f control mice. All NemoΔ mice died between 2 and 3 hours after TNF-α stimulation from hepatic failure. (B) TUNEL staining of liver slides before and 2 hours after TNF-α stimulation showing clear positive staining in NemoΔ, but not in Ikk2Δhepa mice. Results are representative of those obtained in mice (n = 6). Original magnification, × 40. (C) Detection of caspase 3–like activity by an enzymatic, fluorometric assay from whole liver protein lysates at different time points after TNF-α stimulation in Ikk2Δhepa, NemoΔ, and control littermates. Values are mean ± SD for independent animals (n = 6). (D) ALT levels as markers for liver injury at different time points following ConA injection into Ikk2Δhepa and Ikk2^f/f mice. Values are mean ± SD for independent animals (n = 6). (E) ALT levels following Fas-stimulating Jo-2 injection into Ikk2Δhepa and Ikk2^f/f mice. Values are mean ± SD for independent animals (n = 6). U/l, units per liter; AFC, 7-amino-trifluoromethyl coumarin.