Interferon-gamma-oligodendrocyte interactions in the regulation of experimental autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE) is an animal model of the human demyelinating disorder multiple sclerosis (MS). The immune cytokine interferon-gamma (IFN-gamma) is believed to participate in disease pathogenesis in both EAE and MS. In the present study, we examined the significance of IFN-gamma-oligodendrocyte interactions in the course of EAE. For the purpose of our study, we used the previously described [proteolipid protein/suppressor of cytokine signaling 1 (PLP/SOCS1)] transgenic mouse line that displays suppressed oligodendrocyte responsiveness to IFN-gamma. PLP/SOCS1 mice developed EAE with an accelerated onset associated with enhanced early inflammation and markedly increased oligodendrocyte apoptosis. Moreover, we found that IFN-gamma pretreatment of mature oligodendrocytes in vitro had a protective effect against oxidative stress and the inhibition of proteasome activity and resulted in upregulation in expression of a number of chemokines, including CXCL10 (IP10), CCL2 (MCP-1), CCL3 (MCP-1alpha), and CCL5 (RANTES). These results suggest that IFN-gamma-oligodendrocyte interactions are of significance to the clinical and pathological aspects of EAE. In addition, the present study suggests that oligodendrocytes are not simply targets of inflammatory injury but active participants of the neuroimmune network operating during the course of EAE.
Balabanov
Roumen
R
Jack Miller Center for Peripheral Neuropathy and Department of Neurology, The University of Chicago, Chicago, Illinois 60637, USA.
Strand
Krystle
K
Goswami
Rajendra
R
McMahon
Eileen
E
Begolka
Wendy
W
Miller
Stephen D
SD
Popko
Brian
B
D000818:Animals; D000917:Antibody Formation; D017209:Apoptosis; D002478:Cells, Cultured; D002490:Central Nervous System / Q000473:pathology; D018925:Chemokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D018991:Myelin Proteolipid Protein / Q000235:genetics; D009186:Myelin Sheath / Q000473:pathology; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism*; D020286:Pericytes / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics; D013116:Spinal Cord / Q000473:pathology; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics
D018925:Chemokines; D018991:Myelin Proteolipid Protein; D020033:Protein Isoforms; D050826:Suppressor of Cytokine Signaling Proteins; D007371:Interferon-gamma