title: Interleukin-13/-4-induced oxidative stress contributes to death of hippocampal neurons in aβ1-42-treated hippocampus in vivo.
abstract: OBJECTIVE
  The present study examined whether Aβ(1-42) can induce endogenous expression of interleukin-13 (IL-13) or (IL-4) within activated microglia in the rat hippocampus in vivo. We further investigated whether these cytokines mediate ROS/RNS generation through activation of NADPH oxidase and/or inducible nitric oxide synthase (iNOS), and thus contribute to the degeneration of hippocampal neurons in vivo.
  
  
  RESULTS
  Here, we show that IL-13 and IL-4, endogenously expressed in Aβ(1-42)-activated microglia in hippocampus in vivo, contribute to degeneration of hippocampal neurons in vivo. Neutralization of IL-13 and IL-4 protected hippocampal neurons in vivo against neurotoxicity by inhibiting activation of microglial NADPH oxidase and iNOS, resulting in attenuation of ROS generation and oxidative damage of protein, lipid and DNA.
  
  
  METHODS
  To our knowledge, this is the first study to demonstrate the possible involvement of endogenously expressed IL-13 and/or IL-4 in activated microglia after Aβ(1-42) injection in the degeneration of hippocampal neurons in vivo. The current findings suggest that the deleterious effects of microglia-derived endogenous IL-13 and/or IL-4 are involved in oxidative stress-mediated neurodegenerative diseases, such as AD.
  
  
  CONCLUSIONS
  We carefully hypothesize that IL-13 and IL-4, well-known as anti-inflammatory cytokines might serve as neurotoxic mediators by enhancing microglia-derived oxidative stress in Aβ(1-42)-treated hippocampus in vivo.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Nam
authors.forename: K W
authors.initials: KW
authors.lastname: Park
authors.forename: E S
authors.initials: ES
authors.lastname: Park
authors.forename: Y B
authors.initials: YB
authors.lastname: Lee
authors.forename: H G
authors.initials: HG
authors.lastname: Lee
authors.forename: H H
authors.initials: HH
authors.lastname: Baik
authors.forename: Y-S
authors.initials: YS
authors.lastname: Kim
authors.forename: S
authors.initials: S
authors.lastname: Maeng
authors.forename: J
authors.initials: J
authors.lastname: Park
authors.forename: B K
authors.initials: BK
authors.lastname: Jin
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides; D018793:Interleukin-13; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D015847:Interleukin-4