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

// Liang Wang 1, 2 , Bin Li 1, 2 , Mo-Yuan Quan 1, 2 , Lin Li 3 , Yuan Chen 4 , Guo-Jun Tan 1, 2 , Jing Zhang 1, 2 , Xiao-Peng Liu 5 and Li Guo 1, 2 1 Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China 2 Key Laboratory of Hebei Neurology, Shijiazhuang, Hebei 050000, China 3 Department of Neurology, Tongren Hospital of Capital Medical University, Beijing, Hebei 100088, China 4 Department of Pediatrics, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China 5 Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China Correspondence to: Li Guo, email: guoli6@163.com Keywords: oxidative stress, p38MAPK-SGK1, EAE, multiple sclerosis Received: December 08, 2016      Accepted: March 16, 2017      Published: April 12, 2017 ABSTRACT 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.