title: Differential expression of suppressors of cytokine signaling-1 and -3 and related cytokines in central nervous system during remitting versus non-remitting forms of experimental autoimmune encephalomyelitis.
abstract: SJL mice exhibit a relapsing-remitting course of experimental autoimmune encephalomyelitis (EAE), whereas C57BL/6 (B6) mice display a more chronic course without complete remissions. Suppressor of cytokine signaling (SOCS)-1 and SOCS-3 are members of a family of inducible intracellular proteins that negatively regulate cytokine signaling in cells of hematopoietic origin and may influence the Th1 to Th2 balance. SOCS-1 and SOCS-3 are induced by cytokines that are known to be up-regulated during EAE, including IFN-gamma (IFN-g) and IL-6, respectively. To test the hypothesis that the level of induction of SOCS-1 and SOCS-3 correlates with the course of EAE, mRNA levels were compared in spinal cords of SJL and B6 mice during discrete stages of disease. SOCS-1 and SOCS-3 were elevated throughout active disease in both strains. At peak EAE, SOCS-1 was higher and SOCS-3 was lower in B6 cords compared with SJL cords. This correlated with greater expression of the Th1 cytokine, IFN-g, and less of the Th2 cytokine, IL-10, in B6 cords relative to SJL cords during onset and peak disease. SOCS-3 inducers in the IL-6 family were expressed differentially between the strains. IL-6 and leukemia inhibitory factor were higher at onset in B6 cords whereas ciliary neurotrophic factor was increased in SJL cords during peak disease. Expression of fibroblast growth factor-2, which may be involved in remyelination, was higher in SJL cords at peak. Comparison of these models suggests that cytokine autoregulatory mechanisms involving SOCS may play a role in determining the course of EAE.
authors.affiliation: Department of Neurology and Neurosurgery, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8111, Saint Louis, MO 63110, USA. starkj@neuro.wustl.edu
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Stark
authors.forename: Anne H
authors.initials: AH
authors.lastname: Cross
mesh_terms: D000818:Animals; D020934:Ciliary Neurotrophic Factor / Q000096:biosynthesis; D016207:Cytokines; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006133:Growth Substances / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D013116:Spinal Cord / Q000276:immunology* / Q000378:metabolism; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D020934:Ciliary Neurotrophic Factor; D016207:Cytokines; D006133:Growth Substances; D015850:Interleukin-6; C108944:SOCS1 protein, human; C106644:SOCS3 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins