title: The influence of AAV2-mediated gene transfer of human IL-10 on neurodegeneration and immune response in a murine model of Parkinson's disease.
abstract: BACKGROUND
  The aim of this study was to examine the effect of AAV2-hIL-10 (vector containing cDNA for human interleukin 10) on dopaminergic system activity (measured as DA levels and TH mRNA expression in mouse striata), and other monoamine and amino acid neurotransmitters concentration as well as development of inflammatory processes (measured as TGF-β, IFN-γ and GFAP mRNA expression) in a murine MPTP neurotoxicant model of Parkinson's disease.
  
  
  METHODS
  Male C57BL/6 mice 12 months-old were used in this study. AAV2-hIL-10 vector was bilaterally administered into striatum at 14, 21 or 28 days prior to MPTP intoxication. Animals were sacrificed at 7 days following MPTP injection. The expression of hIL-10 (human interleukin 10) was examined by ELISA. Striatal monoamine and amino acid neurotransmitters were measured by HPLC method. TH, TGF-β, IFN-γ and GFAP mRNA expression was examined by RT-PCR method.
  
  
  RESULTS
  MPTP treatment dramatically reduced DA levels and decreased TH mRNA expression in mouse striata, effects that were significantly impeded by AAV2-hIL-10 administration prior to MPTP intoxication. AAV2-hIL-10 infusion increased IFN-γ, TGF-β and GFAP mRNA expression.
  
  
  CONCLUSIONS
  Our data suggest that the transfer of AAV2-hIL-10 into the striatum may play a neuroprotective role in the mouse MPTP model of PD and these effects are mediated by the anti-inflammatory action of IL-10.
authors.affiliation: Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland. Electronic address: ilona.joniec@wum.edu.pl.
authors.forename: Ilona
authors.initials: I
authors.lastname: Joniec-Maciejak
authors.affiliation: Department of Neurosurgery, University of California at San Francisco, San Francisco, CA, USA.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Ciesielska
authors.affiliation: Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Adriana
authors.initials: A
authors.lastname: Wawer
authors.affiliation: Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Sznejder-Pachołek
authors.affiliation: Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Schwenkgrub
authors.affiliation: Second Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Cudna
authors.affiliation: Department of Neurosurgery, University of California at San Francisco, San Francisco, CA, USA.
authors.forename: Piotr
authors.initials: P
authors.lastname: Hadaczek
authors.affiliation: Department of Neurosurgery, University of California at San Francisco, San Francisco, CA, USA.
authors.forename: Kristof S
authors.initials: KS
authors.lastname: Bankiewicz
authors.affiliation: Second Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Członkowska
authors.affiliation: Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Członkowski
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000229:Dependovirus / Q000235:genetics*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D008297:Male; D008810:Mice, Inbred C57BL; D020734:Parkinsonian Disorders / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: C508609:IL10 protein, human; D016753:Interleukin-10; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine
keywords: Adeno-associated virus; Inflammation; MPTP; Neuroprotection; Parkinson's disease