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

Figure 3 C5aRa further lessens the pathogenic effect on D-GalN/LPS challenged mice receiving cobra venom factor pretreatment. A: Cobra venom factor (CVF) treatment decreased serum levels of ALT at 12 h and 24 h significantly (3798.28 IU/L ± 839.68 IU/L vs 7612.78 IU/L ± 1379.21 IU/L, 1965.93 IU/L ± 371.74 IU/L vs 3798.28 IU/L ± 839.68 IU/L, t = 8.34 and 8.18, respectively, ^eP < 0.001); B: Kaplan-Meier analysis of the effect of CVF on survival rates of animals (^eP < 0.001, log-rank test, F = 14.84); C: C5aRa further decreased serum levels of ALT at 12 h and 24 h significantly compared with CVF (1668.4 IU/L ± 339.68 IU/L vs 3798.28 IU/L ± 839.68 IU/L, 1069.69 IU/L ± 171.74 IU/L vs 1965.93 IU/L ± 371.74 IU/L, t = 8.14 and 7.58, respectively, ^eP < 0.001); D: C5aRa further reduced serum levels of TNF-α, IL-1β and IL-6 at 12 h significantly compared with CVF (129.67 pg/mL ± 32.79 pg/mL vs 312.19 pg/mL ± 51.25 pg/mL; 27.73 pg/mL ± 8.78 pg/mL vs 63.28 pg/mL ± 13.27 pg/mL; 103.66 pg/mL ± 22.33 pg/mL vs 223.67 pg/mL ± 41.77 pg/mL, t = 10.39, 7.74, and 8.78, respectively, ^eP < 0.001); E: C5aRa further reduced HMGB1 levels at 6, 12 and 24 h in ALF mice (15.14 ng/mL ± 3.08 ng/mL vs 33.23 ng/mL ± 4.17 ng/mL; 16.21 ng/mL ± 3.11 ng/mL vs 39.44 ng/mL ± 5.07 ng/mL; 15.42 ng/mL ± 3.23 ng/mL vs 31.33 ng/mL ± 4.36 ng/mL, t = 11.49, 13.53, and 10.16, respectively, ^eP < 0.001). ALF: Acute liver failure. TNF: Tumor necrosis factor; IL: Interleukin; ALT: Alanine aminotransferase; HMGB1: High-mobility group protein B1.