Apolipoprotein E-specific innate immune response in astrocytes from targeted replacement mice Public Deposited

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Creator
  • Maeda, Nobuyo
    • Affiliation: School of Medicine, Department of Pathology and Laboratory Medicine
  • Montine, Kathleen S
    • Other Affiliation: Department of Pathology, University of Washington, Seattle, WA, USA
  • Montine, Thomas J
    • Other Affiliation: Department of Pathology, University of Washington, Seattle, WA, USA
  • Maezawa, Izumi
    • Other Affiliation: Department of Pathology, University of Washington, Seattle, WA, USA
Abstract
  • 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 β 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 ε4 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-κB) 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-κB subunit activity. Conclusion: 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-κB signaling in these two cell types.
Date of publication
Identifier
  • doi:10.1186/1742-2094-3-10
  • 16603079
Resource type
  • Article
Rights statement
  • In Copyright
Rights holder
  • Izumi Maezawa et al.; licensee BioMed Central Ltd.
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Journal title
  • Journal of Neuroinflammation
Journal volume
  • 3
Journal issue
  • 1
Page start
  • 10
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1742-2094
Bibliographic citation
  • Journal of Neuroinflammation. 2006 Apr 07;3(1):10
Access
  • Open Access
Publisher
  • BioMed Central Ltd
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