title: Activity, but not mRNA expression of gelatinases correlates with susceptibility to experimental autoimmune encephalomyelitis.
abstract: Experimental autoimmune encephalomyelitis (EAE) is a model of multiple sclerosis (MS), inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS). Clinically manifested EAE can be induced in Dark Agouti (DA) rats, but not in Albino Oxford (AO) rats by immunization with spinal cord homogenate (SCH) and complete Freund's adjuvant (CFA). Matrix metalloproteinases (MMP) play important roles in various steps of MS and EAE pathogenesis. Expression of gelatinases MMP2 and MMP9, their activator MMP14 and their inhibitor tissue inhibitor of MMP (TIMP)1 in the CNS of AO and DA rats immunized with SCH+CFA was determined. Expression of mRNA for MMP2, MMP9 and MMP14 was higher and expression of TIMP1 mRNA was lower in AO rats. However, gelatinase activity in spinal cords was higher in samples obtained from DA rats. Further, while there was no strain difference in MMP2 and MMP9 mRNA expression in lymph nodes of the immunized rats, gelatinase activity was higher in DA rats. This activity was reduced by antiinflammatory cytokines interleukin (IL)-10 and IL-4. Interestingly, gelatinase activity was detected in the nuclei of cells within the CNS, but not of those in lymph nodes. Our results imply that posttranscriptional regulation of MMP2 and MMP9 expression and/or function determines low gelatinase activity within the CNS and in immune cells of EAE-resistant AO rats.
authors.affiliation: Department of Immunology, Institute for Biological Research "Siniša Stanković", University of Belgrade, Serbia.
authors.forename: F
authors.initials: F
authors.lastname: Petković
authors.affiliation: Department of Cytology, Institute for Biological Research "Siniša Stanković", University of Belgrade, Serbia.
authors.forename: J
authors.initials: J
authors.lastname: Živanović
authors.affiliation: Department of Immunology, Institute for Biological Research "Siniša Stanković", University of Belgrade, Serbia.
authors.forename: J
authors.initials: J
authors.lastname: Blaževski
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Serbia.
authors.forename: G
authors.initials: G
authors.lastname: Timotijević
authors.affiliation: Department of Immunology, Institute for Biological Research "Siniša Stanković", University of Belgrade, Serbia.
authors.forename: M
authors.initials: M
authors.lastname: Momčilović
authors.affiliation: Institute of Medical and Clinical Biochemistry, School of Medicine, University of Belgrade, Serbia.
authors.forename: Ž
authors.initials: Ž
authors.lastname: Stanojević
authors.affiliation: Center for Laser Microscopy, Department of Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Serbia.
authors.forename: V
authors.initials: V
authors.lastname: Stamenković
authors.affiliation: Department of Cytology, Institute for Biological Research "Siniša Stanković", University of Belgrade, Serbia.
authors.forename: V
authors.initials: V
authors.lastname: Milošević
authors.affiliation: Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Serbia.
authors.forename: M
authors.initials: M
authors.lastname: Mostarica Stojković
authors.affiliation: Department of Immunology, Institute for Biological Research "Siniša Stanković", University of Belgrade, Serbia. Electronic address: georgije_zw@yahoo.com.
authors.forename: Đ
authors.initials: Đ
authors.lastname: Miljković
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000201:enzymology*; D020022:Genetic Predisposition to Disease; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008198:Lymph Nodes / Q000201:enzymology; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013116:Spinal Cord / Q000201:enzymology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*
chemical_list: C000603532:Mmp14 protein, rat; D012333:RNA, Messenger; C576839:TIMP1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1; D016753:Interleukin-10; D015847:Interleukin-4; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; D053511:Matrix Metalloproteinase 14
keywords: experimental autoimmune encephalomyelitis; gelatinase; matrix metalloproteinase; neuroinflammation; rat