Activation of mitogen-activated protein kinases in experimental autoimmune encephalomyelitis

J Neuroimmunol. 2003 Jul;140(1-2):118-25. doi: 10.1016/s0165-5728(03)00174-7.


The expression of mitogen-activated protein (MAP) kinases, including extracellular signal-regulated kinase (ERK), c-Jun NH(2)-terminal protein kinase (JNK), and p38, was analyzed in experimental autoimmune encephalomyelitis (EAE) in rats. Western blot analysis showed that the three MAP kinases (phosphorylated ERK (p-ERK), p-JNK, and p-p38) were increased significantly in the spinal cords of rats with EAE at the peak stage as compared with the levels in controls (p<0.05), and both p-ERK and p-JNK declined slightly in the recovery stage of EAE. Immunohistochemistry showed that p-ERK was constitutively expressed in brain cells, including astroglial cells, and showed enhanced immunoreactivity in those cells in EAE, while some T cells and macrophages were weakly immunopositive for p-ERK in EAE lesions. Both p-JNK and p-p38 were intensely immunostained in T cells in EAE lesions, while a few glial cells and astrocytes were weakly positive for both. Taking all these facts into consideration, we postulate that increased expression of the phosphorylated form of each MAP kinase plays an important role in the initiation of acute monophasic EAE. Differential expression of three MAP kinases was discerned in an animal model of human autoimmune central nervous system diseases, including multiple sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / enzymology
  • Astrocytes / pathology
  • Blotting, Western
  • Cell Movement / immunology
  • Encephalomyelitis, Autoimmune, Experimental / enzymology*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / pathology
  • Enzyme Activation / immunology
  • Female
  • Immunohistochemistry
  • JNK Mitogen-Activated Protein Kinases*
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Mitogen-Activated Protein Kinases / metabolism*
  • Phosphorylation
  • Rats
  • Rats, Inbred Lew
  • Spinal Cord / enzymology
  • Spinal Cord / pathology
  • T-Lymphocyte Subsets / enzymology
  • T-Lymphocyte Subsets / pathology
  • p38 Mitogen-Activated Protein Kinases


  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases