C5a/C5aR pathway is essential for up-regulating SphK1 expression through p38-MAPK activation in acute liver failure

Figure 2 C5aRa attenuates D-GalN/LPS induced acute liver failure in mice. A: C5aRa decreased serum levels of ALT at 12 h and 24 h significantly (3736.12 IU/L ± 937.98 IU/L vs 7612.78 IU/L ± 1379.21 IU/L, 2225.07 IU/L ± 381.99 IU/L vs 3741.74 IU/L ± 637.53 IU/L, t = 8.05 and 7.07, respectively, ^eP < 0.001); B: C5aRa reduced serum levels of TNF-α, IL-1β and IL-6 at 12 h (299.35 pg/mL ± 50.61 pg/mL vs 439.33 pg/mL ± 63.59 pg/mL, 57.42 pg/mL ± 12.98 pg/mL vs 106.69 pg/mL ± 49.87 pg/mL, 213.52 pg/mL ± 42.69 pg/mL vs 500.87 pg/mL ± 104.14 pg/mL, t = 5.96, 6.94, and 8.84 respectively, ^eP < 0.001); C: C5aRa reduced HMGB1 levels at 6, 12 and 24 h (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, ^eP < 0.001); D: Immune cell infiltration and tissue damage were detected by HE staining at 36 h after onset of ALF (1 = normal mice; 2 = ALF mice; 3 = C5aRa treated mice; magnification, × 100); E: Kaplan-Meier analysis of the effect of C5aRa on survival rates of animals (^eP < 0.001, log-rank test, F = 14.06). The mean ± SE of three independent experiments is shown (error bar indicates standard error). ALF: Acute liver failure. TNF-α: Tumor necrosis factor-α; IL: Interleukin.