Inhibition of p38 mitogen-activated protein kinase attenuates experimental autoimmune hepatitis: Involvement of nuclear factor kappa B

Figure 1 Increased activity of p38MAPK and NF-κB in EAH liver. A: Expression of phosphor-p38 MAPK protein by Western blot in whole liver extract; B:Expression of total p38 MAPK protein by Western blot in whole liver extract; C: Immunoprecipitate kinase activity assays of p38 MAPK; D: Electrophoretic mobility shift assay of NF-κB DNA binding activity using nuclear protein extracts from EAH liver.

Figure 2 Effects of SB203580, a specific p38 MAPK inhibitor, on the activation of p38 MAPK and NF-κB 14 d after the first immunization. A: Representative immunoprecipitate kinase activity assays of p38 MAPK using protein extracts from normal control, EAH mice treated with PBS, DMSO, and SB 203580, respectively; B: Western bolt of total p38 MAPK; C: Representative electrophoretic mobility shift assays of NF-κB DNA binding activity using nuclear protein extracts from liver of the 4 study groups as in A.

Figure 3 Effects of SB203580, a specific p38 MAPK inhibitor, on the expression of proinflammatory cytokines. Northern blot of IFN-γ, IL-12, IL-1β and TNF-α from total liver RNA isolated from normal control, EAH mice treated with PBS, DMSO, and SB203580, respectively. The same blot was striped and reprobed with β-actin as an internal loading control.

Figure 4 Effects of SB203580, a specific p38 MAPK inhibitor, on hepatic inflammation in EAH. A: Representative histology of control animals after standard induction of EAH showing portal inflammation (grade 2); B: Representative histology of animals treated with SB203580 after standard induction of EAH showing significantly reduced portal inflammation (grade 1); C: Average histological inflammation grade score for PBS, DMSO and SB203580 treated animals after standard induction of EAH (^aP < 0.05 between PBS and SB203580 treated animals); D: Serum alanine transaminase (ALT) levels in PBS, DMSO and SB203580 treated animals after standard induction of EAH (^aP < 0.05 between PBS and SB203580 treated animals).