Sphingosine kinase 1 dependent protein kinase C-δ activation plays an important role in acute liver failure in mice

Figure 3 Inhibition of protein kinase C-δ activity with rottlerin down-regulates serum levels of inflammatory cytokines and reduces immune cell infiltration and tissue damage in mice with acute liver failure. A: Rottlerin reduced serum levels of TNF-α, IL-1β and IL-6 significantly (77.22 pg/mL ± 28.56 pg/mL vs 211.21 pg/mL ± 49.13 pg/mL; 15.79 pg/mL ± 7.66 pg/mL vs 39.83 pg/mL ± 18.78 pg/mL; 19.25 pg/mL ± 5.23 pg/mL vs 49.44 pg/mL ± 10.77 pg/mL, t = 8.16, 4.10 and 8.73, respectively, ^bP < 0.01), but did not increase the anti-inflammatory cytokine IL-10 level at 12 h; B: Rottlerin reduced HMGB1 levels at 6, 12 and 24 h in mice (18.14 ng/mL ± 4.08 ng/mL vs 60.23 ng/mL ± 5.47 ng/mL; 16.21 ng/mL ± 5.11 ng/mL vs 67.14 ng/mL ± 14.27 ng/mL; 15.42 ng/mL ± 6.23 ng/mL vs 48.71 ng/mL ± 15.6 ng/mL, t = 9.13, 11.64 and 6.85, respectively, ^bP < 0.01); C: Normal mice; D: Acute liver failure mice; E: Rottlerin treated mice. The mean ± SE of three independent experiments is shown (error bar indicates SE). Immune-cell infiltration and tissue damage at 36 h after induction of acute liver failure were detected by H&E staining (magnification, × 100). TNF: Tumor necrosis factor; IL: Interleukin.