STAT expression and localization in the central nervous system during autoimmune encephalomyelitis in Lewis rats.
Autoimmune inflammation in the central nervous system (CNS) is maintained by secretion of a large number of cytokines. To elucidate its molecular mechanisms, we examined the expression and localization of STAT1, STAT3, STAT4 and STAT6 molecules, which are the downstream molecules of the cytokine signal transduction pathway, in the CNS during acute experimental autoimmune encephalomyelitis (EAE) induced in Lewis rats. Western blot analysis demonstrated that STAT1 protein increased gradually till the recovery stage, whereas STAT4 protein showed abrupt increase at the early stage followed by gradual decrease. STAT3 and STAT6 showed stable expression throughout the course of the disease. The kinetics of the phosphorylated form of STAT1 and STAT4 roughly paralleled that of the total protein although the peak of STAT3 phosphorylation was recognized at the preclinical stage. Immunohistochemical examinations revealed that STAT3 and STAT4, but not STAT1 and STAT6, immunoreactivities were mainly expressed in astrocytes and microglia, respectively, and were closely associated with inflammatory lesions. Taken together, these findings suggest that STAT3 and STAT4 play an important role in the formation of, and recovery from, autoimmune inflammation in the CNS.
Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo, Japan
Y
Y
Jee
G
G
Kim
N
N
Tanuma
Y
Y
Matsumoto
D000818:Animals; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism; D007150:Immunohistochemistry; D007700:Kinetics; D010766:Phosphorylation; D051381:Rats; D011917:Rats, Inbred Lew; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050797:STAT4 Transcription Factor; D050800:STAT6 Transcription Factor; D013116:Spinal Cord / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D015534:Trans-Activators / Q000032:analysis / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D004268:DNA-Binding Proteins; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050797:STAT4 Transcription Factor; D050800:STAT6 Transcription Factor; C494081:Stat1 protein, rat; C494088:Stat3 protein, rat; D015534:Trans-Activators; D014443:Tyrosine