Objective: Investigation of the role of the mitogen-activated proteinkinase activated proteinkinase 2 in experimental autoimmune encephalomyelitis. Background The p38 mitogen-activated protein kinase pathway mediates cellular responses to injurious stress and immune signaling. The downstream targets of p38 MAPK include the mitogen-activated proteinkinase activated proteinkinase (MK) 2. Recently, the role of MK2 has been studied in models of inflammatory or degenerative diseases. The findings suggest that a lack of MK2 reduces inflammation and protects against destruction of the brain and other tissues. Thus, we investigated the role of MK2 in experimental autoimmune encephalomyelitis (EAE). Design/Methods: EAE was induced in MK2 knockout mice (MK2-/-) and wildtype controls by immunization with MOG35-55 in CFA. Animals were observed over a period of 24 days. The inflammation and demyelination was estimated by histology and immunohistochemistry in the acute phase of the disease. Moreover, cells isolated from the CNS were counted and TNFα serum level was assigned by ELISA in different stages of EAE. Results: Contrary to expectance, MK2-/- had more severe disease signs correlating with an increased number of cells in the CNS. There was no difference in the onset of EAE and both groups developed paresis in the early phase of the disease. From day 18 post immunization wildtype controls showed significantly improved locomotor recovery compared to MK2-/-. The histological examination of CNS sections in the acute phase showed that there was no difference in demyelination but MK2-/- had more CD4 and CD8 positive cells in the CNS. Moreover, we found a reduced level of the inflammation mediator TNFα. Conclusions: In contrast to the expectations, the MK2-/- aggravated the disease course and was associated with more inflammation. The reason for these findings may partially be explained by differences in TNFα biosynthesis and therefore a changed apoptosis characteristic in autoreactive cells in the CNS of MK2-/- mice. Disclosure: Dr. Tietz has nothing to disclose. Dr. Viard has nothing to disclose. Dr. Thomas has nothing to disclose. Dr. Gaestel has nothing to disclose. Dr. Berghoff has received personal compensation for activities with Bayer Vital GmbH, Merck Serono, TEVA Neuroscience and Biogen Idec as a speaker. Dr. Berghoff has received research support from Bayer Vital GmhB, TEVA Neuroscience, Merck Serono and Biogen Idec.
Read full abstract