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

AIM

To investigate the role of p38 mitogen-activated protein kinase (p38MAPK) in murine experimental autoimmune hepatitis (EAH).

METHODS

To induce EAH, the syngeneic S-100 antigen emulsified in complete Freud's adjuvant was injected intraperitoneally into adult male C57Bl/6 mice. Liver injury was assessed by serum ALT and liver histology. The expression and activity of p38 MAPK were measured by Western blot and kinase activity assays. In addition, DNA binding activities of nuclear factor kappa B (NF-kappaB) were analyzed by electrophoretic mobility shift assay. The effects of SB203580, a specific p38 MAPK inhibitor, on liver injuries and expression of proinflammatory cytokines (interferon-gamma, IL-12, IL-1beta and TNF-alpha) were observed.

RESULTS

The activity of p38 MAPK and NF-kappaB was increased and reached its peak 14 or 21 d after the first syngeneic S-100 administration. Inhibition of p38 MAPK activation by SB203580 decreased the activation of NF-kappaB and the expression of proinflammatory cytokines. Moreover, hepatic injuries were improved significantly after SB203580 administration.

CONCLUSION

p38 MAPK and NF-kappaB play an important role in an animal model of autoimmune hepatitis (AIH) induced by autoantigens.