title: Apolipoprotein E-specific innate immune response in astrocytes from targeted replacement mice.
abstract: BACKGROUND
  Inheritance of the three different alleles of the human apolipoprotein (apo) E gene (APOE) are associated with varying risk or clinical outcome from a variety of neurologic diseases. ApoE isoform-specific modulation of several pathogenic processes, in addition to amyloid beta metabolism in Alzheimer's disease, have been proposed: one of these is innate immune response by glia. Previously we have shown that primary microglia cultures from targeted replacement (TR) APOE mice have apoE isoform-dependent innate immune activation and paracrine damage to neurons that is greatest with TR by the epsilon4 allele (TR APOE4) and that derives from p38 mitogen-activated protein kinase (p38MAPK) activity.
  
  
  METHODS
  Primary cultures of TR APOE2, TR APOE3 and TR APOE4 astrocytes were stimulated with lipopolysaccharide (LPS). ApoE secretion, cytokine production, and nuclear factor-kappa B (NF-kappaB) subunit activity were measured and compared.
  
  
  RESULTS
  Here we showed that activation of primary astrocytes from TR APOE mice with LPS led to TR APOE-dependent differences in cytokine secretion that were greatest in TR APOE2 and that were associated with differences in NF-kappaB subunit activity.
  
  
  CONCLUSIONS
  Our results suggest that LPS activation of innate immune response in TR APOE glia results in opposing outcomes from microglia and astrocytes as a result of TR APOE-dependent activation of p38MAPK or NF-kappaB signaling in these two cell types.
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA, USA. imaezawa@u.washington.edu
authors.forename: Izumi
authors.initials: I
authors.lastname: Maezawa
authors.forename: Nobuyo
authors.initials: N
authors.lastname: Maeda
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Montine
authors.forename: Kathleen S
authors.initials: KS
authors.lastname: Montine