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

Izumi Maezawa, Nobuyo Maeda, Thomas J. Montine, Kathleen S. Montine

Research output: Contribution to journalArticle

51 Citations (Scopus)

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.

Original languageEnglish (US)
Article number10
JournalJournal of Neuroinflammation
Volume3
DOIs
StatePublished - Apr 7 2006
Externally publishedYes

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Apolipoproteins E
Innate Immunity
Astrocytes
NF-kappa B
Lipopolysaccharides
Genes
Microglia
p38 Mitogen-Activated Protein Kinases
Neuroglia
Protein Isoforms
Alleles
Cytokines
Nervous System Diseases
Amyloid
Transcriptional Activation
Alzheimer Disease
Neurons

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Apolipoprotein E-specific innate immune response in astrocytes from targeted replacement mice. / Maezawa, Izumi; Maeda, Nobuyo; Montine, Thomas J.; Montine, Kathleen S.

In: Journal of Neuroinflammation, Vol. 3, 10, 07.04.2006.

Research output: Contribution to journalArticle

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