Mechanism of oxidative stress p38MAPK-SGK1 signaling axis in experimental autoimmune encephalomyelitis (EAE)
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Liang Wang1,2, Bin Li1,2, Mo-Yuan Quan1,2, Lin Li3, Yuan Chen4, Guo-Jun Tan1,2, Jing Zhang1,2, Xiao-Peng Liu5 and Li Guo1,2
1Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
2Key Laboratory of Hebei Neurology, Shijiazhuang, Hebei 050000, China
3Department of Neurology, Tongren Hospital of Capital Medical University, Beijing, Hebei 100088, China
4Department of Pediatrics, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
5Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
Li Guo, email: email@example.com
Keywords: oxidative stress, p38MAPK-SGK1, EAE, multiple sclerosis
Received: December 08, 2016 Accepted: March 16, 2017 Published: April 12, 2017
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.
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