Proinflammatory cytokine interferon-γ increases induction of indoleamine 2,3-dioxygenase in monocytic cells primed with amyloid β peptide 1-42

Implications for the pathogenesis of Alzheimer's disease

Akiko Yamada, Hidetoshi Akimoto, Syota Kagawa, Gilles J. Guillemin, Osamu Takikawa*

*Corresponding author for this work

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Indoleamine 2,3-dioxygenase (IDO) is the rate-limiting enzyme of the kynurenine pathway of tryptophan metabolism, ultimately leading to production of the excitotoxin quinolinic acid (QUIN) by monocytic cells. In the Tg2576 mouse model of Alzheimer's disease, systemic inflammation induced by lipopolysaccharide leads to an increase in IDO expression and QUIN production in microglia surrounding amyloid plaques. We examined whether the IDO over-expression in microglia could be mediated by brain proinflammatory cytokines induced during the peripheral inflammation using THP-1 cells and peripheral blood mononuclear cells (PBMC) as models for microglia. THP-1 cells pre-treated with 5-25 μM amyloid β peptide (Aβ) (1-42) but not with Aβ (1-40) or Aβ (25-35) became an activated state as indicated by their morphological changes and enhanced adhesiveness. IDO expression was only slightly increased in the reactive cells but strongly enhanced following treatment with proinflammatory cytokine interferon-γ (IFN-γ) but not with interleukin-1β, tumor necrosis factor-α, or interleukin-6 at 100 U/mL. The concomitant addition of Aβ (1-42) with IFN-γ was totally ineffective, indicating that Aβ pre-treatment is prerequisite for a high IDO expression. The priming effect of Aβ (1-42) for the IDO induction was also observed for PBMC. These findings suggest that IFN-γ induces IDO over-expression in the primed microglia surrounding amyloid plaques.

Original languageEnglish
Pages (from-to)791-800
Number of pages10
JournalJournal of Neurochemistry
Volume110
Issue number3
DOIs
Publication statusPublished - Aug 2009
Externally publishedYes

Fingerprint Dive into the research topics of 'Proinflammatory cytokine interferon-γ increases induction of indoleamine 2,3-dioxygenase in monocytic cells primed with amyloid β peptide 1-42: Implications for the pathogenesis of Alzheimer's disease'. Together they form a unique fingerprint.

Cite this