Treatment of experimental autoimmune encephalomyelitis with a neurotropic alphavirus vector expressing tissue inhibitor of metalloproteinase-2

Scandinavian Journal of Immunology
P T NygårdasAri E Hinkkanen

Abstract

Prompted by our recent observations of increased MMP-8 and MMP-9 with simultaneous downregulation of tissue inhibitor of metalloproteinase-2 (TIMP-2) and TIMP-3 mRNA levels in the central nervous system (CNS) of mice with severe experimental autoimmune encephalomyelitis (EAE), we used Semliki Forest virus (SFV) to transfer and express recombinant murine TIMP-1-3 genes in the CNS. TIMP-1, TIMP-2 and TIMP-3 expression was confirmed in cultured cells and in the CNS of infected mice. Following intraperitoneal infection with 10(6) plaque-forming units (PFU) of SFV-TIMP, focal TIMP protein expression was achieved throughout the brain. Although already treatment with empty vector inhibited development of EAE to some extent, the expression of TIMP-2 by the virus significantly enhanced the inhibition. TIMP-3-administered mice also had lower disease grade, but the inhibition was not statistically significant. In contrast, SFV-TIMP-1 had no effect, similar to co-infection with TIMP-2 and TIMP-3. We found TIMP-2 expression also by non-infected CNS-resident cells surrounding the virus-positive areas, suggesting a bystander TIMP-2 induction. These data strengthen the view that matrix metalloproteinases are involved in the pathogenesis of EAE...Continue Reading

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Citations

Nov 13, 2008·Expert Reviews in Molecular Medicine·Gregory J AtkinsBrian J Sheahan
Oct 30, 2008·Journal of Immunotoxicology·Sarah J BlossomKathleen M Gilbert
Dec 8, 2007·Journal of Neuroimmunology·Elizabeth MilwardKatherine Conant
Feb 24, 2007·Biochemical and Biophysical Research Communications·Markus J V Vähä-KoskelaAri E Hinkkanen
Aug 27, 2015·Virus Research·Kenneth Lundstrom
Oct 29, 2011·The American Journal of Pathology·Craig S Moore, Stephen J Crocker
Jun 1, 2009·Viruses·Kenneth Lundstrom
Apr 20, 2007·International Journal of Cancer. Journal International Du Cancer·Ann-Marie MäättäJarmo Wahlfors
Feb 16, 2006·Cardiology·Mutlu Vural, Kultegin Ogel

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