Fig. 5
BMSCs decrease inflammatory cytokines via HO-1 in the setting of ALF. a Western blot of phosphorylated P38 mitogen-activated protein kinase (MAPK), extracellular-regulated protein kinases (Erk), C-Jun N-terminal kinase (JNK), nuclear factor kappa B (NF-κB) p65 (and β-actin standard). Levels of JNK, p-p38, NF-κB p65 increased in ALF livers vs. controls. BMSCs decreased ALF levels of JNK, NF-κB p65; Znpp only blunted the BMSC inhibition of NF-κB p65 expression. Hemin treatment also resulted only in reduction of NF-kB p65 protein. b NF-κB DNA binding activity (n = 6 per group) increased significantly in ALF livers. BMSCs significantly reduced NF-κB DNA binding activity (p < 0.05). Znpp administration could reverse this BMSC effect (p < 0.05). Hemin and BMSC were also associated with decreased NF-κB DNA binding activity vs. ALF livers (p < 0.05). c Enzyme-linked immunosorbent assay of serum levels of IL-1β, IL-6, and TNF-α after D-Gal/LPS (n = 6 per group). Quantitative reverse transcription PCR for IL-1β, IL-6, and TNF-α mRNA levels in livers. BMSCs infusion significantly decreased protein or mRNA levels of IL-1β, IL-6, and TNF-α (p < 0.05); Znpp administration reversed this effect of the BMSCs (p < 0.05). Hemin and BMSCs were also associated with decreased protein and mRNA levels of IL-1β, IL-6, and TNF-α (p < 0.05) vs. ALF livers. Treatment groups: control, ALF, ALF followed by intravenous MSCs (ALF + MSC) 1 h post-induction, ALF followed by MSCs and Znpp (ALF + MSC + Znpp) 1 h post-induction, and ALF followed by hemin (ALF + hemin) 1 h post-induction. Data are mean ± SD. (* p < 0.05 vs. control group; $ p < 0.05 vs. ALF group; # p < 0.05 vs. ALF + MSC group). Abbreviations: ALF acute liver failure, BMSCs bone marrow-derived mesenchymal stem cells, D-Gal d-Galactosamine, HO-1 heme oxygenase-1, IL interleukin, LPS lipopolysaccharide, TNF tumor necrosis factor, Znpp zinc protoporphyrin