Mechanism of oxidative stress p38MAPK-SGK1 signaling axis in experimental autoimmune encephalomyelitis (EAE)

BACKGROUND Multiple sclerosis (MS), a complex disease associated with multifocal demyelination of the central nervous system and poorly understood etiology. It has been previously indicated that many factors, including oxidative stress and p38MAPK-SGK1 pathway, contribute to the pathogenesis of MS. METHODS This study, using an experimental autoimmune encephalomyelitis (EAE) model system, was aimed at investigating the molecular mechanisms determining interaction p38MAPK-SGK1 pathway and oxidative stress in MS pathogenesis. C57BL/6 mice was immunized with MOG35-55 peptide for EAE induction, which was followed by determination of the effect of treatment with classic p38 inhibitor SB203580 and antioxidant tempol on the development and progression of EAE. RESULTS Our experiments showed a dynamic change of immune inflammation, oxidative stress and p38MAPK-SGK1 pathway involvement in EAE demonstrating that p38MAPK-SGK1 pathway and oxidative stress contribute to the demyelination in central nerve system caused by Th17 inflammatory responses in a synergistic way. The administration of SB203580 and Tempol both markedly suppressed the progression of EAE. Furthermore, tempol showed a strong inhibiting effect to the p38MAPK-SGK1 pathway similar to SB203580 suggesting that oxidative stress exacerbates EAE via the activation of p38MAPK-SGK1 pathway. CONCLUSION Cumulatively, our results show that oxidative stress p38MAPK-SGK1 signaling pathway may be a central player in EAE and even in MS.