| First Author | Namiki K | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 29 | Pages | 24228-38 |
| PubMed ID | 22637476 | Mgi Jnum | J:188860 |
| Mgi Id | MGI:5442467 | Doi | 10.1074/jbc.M111.338541 |
| Citation | Namiki K, et al. (2012) Mechanism for p38alpha-mediated experimental autoimmune encephalomyelitis. J Biol Chem 287(29):24228-38 |
| abstractText | One of the mitogen-activated protein kinases, p38, has been found to play a crucial role in various inflammatory responses. In this study, we analyzed the roles of p38alpha in multiple sclerosis, using an animal model, experimental autoimmune encephalomyelitis (EAE). p38alpha(+/-) mice (p38alpha(-/-) showed embryonic lethality) showed less severe neurological signs than WT mice. Adoptive transfer of lymph node cells (LNC) from sensitized WT mice with MOG(35-55) to naive WT-induced EAE was much more severe compared with the case using LNC from sensitized p38alpha(+/-) mice. Comprehensive analysis of cytokines from MOG(35-55)-challenged LNC by Western blot array revealed that production of IL-17 was significantly reduced by a single copy disruption of the p38alpha gene or a p38 inhibitor. Likewise, by a luciferase reporter assay, an electrophoresis mobility shift assay, and characterization of the relationship between p38 activity and IL-17 mRNA expression, we confirmed that p38 positively regulates transcription of the Il17 gene. Furthermore, oral administration of a highly specific p38alpha inhibitor (UR-5269) to WT mice at the onset of EAE markedly suppressed the progression of EAE compared with a vehicle group. These results suggest that p38alpha participates in the pathogenesis of EAE through IL-17 induction. |
