title: GM-CSF induces neuroprotective and anti-inflammatory responses in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxicated mice.
abstract: Innate and adaptive immune responses can speed nigrostriatal neurodegeneration in Parkinson's disease (PD). We posit that GM-CSF can attenuate such responses. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mice, GM-CSF given prior to MPTP protected nigral dopaminergic neurons coincident with altered microglial morphologies and regulatory T cell (Treg) induction. Adoptive transfer of GM-CSF-induced Treg to MPTP mice protected nigral neurons. Gene expression analyses revealed novel immune-based neuronal protection pathways linked to the upregulation of IL-27. The results provide evidence that GM-CSF modulation of immunity could be of clinical benefit for PD.
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, Center for Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Kosloski
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Kosmacek
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Olson
authors.forename: R Lee
authors.initials: RL
authors.lastname: Mosley
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D015703:Antigens, CD / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes; D002452:Cell Count; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005786:Gene Expression Regulation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000473:pathology; D020734:Parkinsonian Disorders / Q000473:pathology* / Q000517:prevention & control* / Q000601:surgery; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000601:surgery; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000637:transplantation; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D049452:Green Fluorescent Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D014446:Tyrosine 3-Monooxygenase
keywords: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Innate immunity; Neuroinflammation; Neuroprotection; Parkinson's disease; Regulatory T cells