| First Author | Tietz SM | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 6 | Pages | e100363 |
| PubMed ID | 24964076 | Mgi Jnum | J:216820 |
| Mgi Id | MGI:5609735 | Doi | 10.1371/journal.pone.0100363 |
| Citation | Tietz SM, et al. (2014) MK2 and Fas receptor contribute to the severity of CNS demyelination. PLoS One 9(6):e100363 |
| abstractText | Models of inflammatory or degenerative diseases demonstrated that the protein-kinase MK2 is a key player in inflammation. In this study we examined the role of MK2 in MOG35-55-induced experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis. In MK2-deficient (MK2-/-) mice we found a delayed onset of the disease and MK2-/- mice did not recover until day 24 after EAE induction. At this day a higher number of leukocytes in the CNS of MK2-/- mice was found. TNFalpha was not detectable in serum of MK2-/- mice in any stage of EAE, while high TNFalpha levels were found at day 16 in wild-type mice. Further investigation revealed an increased expression of FasR mRNA in leukocytes isolated from CNS of wild-type mice but not in MK2-/- mice, however in vitro stimulation of MK2-/- splenocytes with rmTNFalpha induced the expression of FasR. In addition, immunocomplexes between the apoptosis inhibitor cFlip and the FasR adapter molecule FADD were only detected in splenocytes of MK2-/- mice at day 24 after EAE induction. Moreover, the investigation of blood samples from relapsing-remitting multiple sclerosis patients revealed reduced FasR mRNA expression compared to healthy controls. Taken together, our data suggest that MK2 is a key regulatory inflammatory cytokines in EAE and multiple sclerosis. MK2-/- mice showed a lack of TNFalpha and thus might not undergo TNFalpha-induced up-regulation of FasR. This may prevent autoreactive leukocytes from apoptosis and may led to prolonged disease activity. The findings indicate a key role of MK2 and FasR in the regulation and limitation of the immune response in the CNS. |
