title: Effects of cytokine deficiency on chemokine expression in CNS of mice with EAE.
abstract: Although both cytokines and chemokines have been implicated in the pathogenesis of clinical and histological EAE, their interactions in vivo have not yet been clearly established. To address this issue, we evaluated expression of chemokines and receptors in the CNS of wild-type control and cytokine deficient mice at the peak of EAE induced with MOG-35-55 peptide in CFA. Our results demonstrate that: 1) expression of most chemokines/receptors was drastically inhibited in TNF-alpha deficient mice, and was reflective of delayed onset and reduced severity of EAE; 2) distinct patterns of chemokine expression occurred in various other cytokine knockout mice that did not significantly affect expression of clinical EAE; 3) there was a strong association between expression of MIP-1alpha, MIP-2 and MCP-1 in CNS and overall severity of EAE in wild-type and cytokine knockout mice; and 4) among CNS infiltrating cells at the peak of EAE, macrophages and CD8+ T cells were the primary cellular source of most of the chemokines. Of note, we present evidence that TNF-alpha may be involved in regulating RANTES and MIP-1alpha, and that IL-4 may be involved in regulating MCP-1. Our results not only identify the cellular source of chemokines in CNS, but also implicate MIP-1alpha, MIP-2, and MCP-1 in controlling CNS inflammation and severity of EAE.
authors.affiliation: Department of Neurology, Oregon Health and Science University, Portland, Oregon, USA.
authors.forename: Agata
authors.initials: A
authors.lastname: Matejuk
authors.forename: Jami
authors.initials: J
authors.lastname: Dwyer
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ito
authors.forename: Zachary
authors.initials: Z
authors.lastname: Bruender
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Vandenbark
authors.forename: Halina
authors.initials: H
authors.lastname: Offner
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism; D054357:Chemokine CXCL10; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism*; D019743:Chemokines, CXC / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000235:genetics; D016207:Cytokines / Q000172:deficiency* / Q000235:genetics; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics; D015847:Interleukin-4 / Q000172:deficiency / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D019707:Receptors, Chemokine / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; C404915:Cxcl2 protein, mouse; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D016177:Macrophage-1 Antigen; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma