title: Sequential expression of chemokines in experimental autoimmune neuritis.
abstract: Recruitment of inflammatory cells is of critical importance in the pathogenesis of immune-mediated demyelinating diseases in the peripheral nervous system (PNS). Evidence is increasing that chemokines might play a key role in this process, since they promote leukocyte entry into the nervous system during immune-mediated inflammation. In the present study we report the expression pattern of the chemokines interferon-gamma-inducible protein (IP)-10, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and regulated upon activation normal T cell expressed and secreted (RANTES) in sciatic nerves from animals with myelin-induced experimental autoimmune neuritis, using a semiquantitative reverse transcriptase-PCR dot-blot hybridization assay. The mRNAs for MIP-1alpha and MIP-1beta were found to be upregulated with peak values at day 13 post-immunization (p.i.), preceding maximum disease severity. In contrast, mRNAs for MCP-1, RANTES, and IP-10 exhibited peak levels coincident with peak of the disease at day 15 p.i. Increased mRNA expression was associated with enhanced protein levels, as demonstrated by immunoblotting for each chemokine investigated. Immunohistochemistry for IP-10 protein revealed immunoreactivity associated with perineurial endothelial cells. RANTES protein was localized immunohistologically to invading T lymphocytes. Our findings suggest that chemokines, which act towards T cells and mononuclear phagocytes, are sequentially upregulated during the clinical course of EAN and thus may contribute to the pathogenesis of inflammatory demyelinating diseases of the PNS.
authors.affiliation: Department of Neurology, Karl-Franzens-Universität, Auenbruggerplatz 22, 8036, Graz, Austria. bc.kieseier@kfunigraz.zc.zt
authors.forename: B C
authors.initials: BC
authors.lastname: Kieseier
authors.forename: K
authors.initials: K
authors.lastname: Krivacic
authors.forename: S
authors.initials: S
authors.lastname: Jung
authors.forename: H
authors.initials: H
authors.lastname: Pischel
authors.forename: K V
authors.initials: KV
authors.lastname: Toyka
authors.forename: R M
authors.initials: RM
authors.lastname: Ransohoff
authors.forename: H P
authors.initials: HP
authors.lastname: Hartung
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000032:analysis / Q000276:immunology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000032:analysis / Q000276:immunology; D054357:Chemokine CXCL10 / Q000032:analysis / Q000235:genetics; D018925:Chemokines / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D003711:Demyelinating Diseases / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D015870:Gene Expression / Q000276:immunology; D020275:Guillain-Barre Syndrome / Q000276:immunology; D019402:Macrophage Inflammatory Proteins / Q000032:analysis / Q000276:immunology; D009443:Neuritis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000737:chemistry / Q000276:immunology*
chemical_list: D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D018925:Chemokines; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger