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
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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Previous work demonstrates that the response of microglia around amyloid plaques in the Tg2576 mouse triggers increased IDO activity because of inflammation.
“Previous work demonstrates that the response of microglia around amyloid plaques in the Tg2576 mouse trigger increased IDO activity because of inflammation [49].”
Cites
RAGE and amyloid-β peptide neurotoxicity in Alzheimer's disease
Yan, S. D., Chen, X., Fu, J., Chen, M., Zhu, H., Roher, A., Slattery, T., Zhao, L., Nagashima, M., Morser, J., et al. (1996) · Nature · doi:10.1038/382685a0 · Cited by 2,012 · see citing works
Iwatsubo, T., Odaka, A., Suzuki, N., Mizusawa, H., Nukina, N., & Ihara, Y. (1994) · Neuron · doi:10.1016/0896-6273(94)90458-8 · Cited by 1,774 · see citing works
Oligomeric and fibrillar species of amyloid-β peptides differentially affect neuronal viability
Dahlgren, K. N., Manelli, A. M., Stine, W. B., Baker, L. K., Krafft, G. A., & LaDu, M. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201750200 · Cited by 1,452 · see citing works
Activation of microglial cells by β-amyloid protein and interferon-γ
Meda, L., Cassatella, M. A., Szendrei, G. I., Otvos, L., Baron, P., Villalba, M., Ferrari, D., & Rossi, F. (1995) · Nature · doi:10.1038/374647a0 · Cited by 1,314 · see citing works
Evans, D. A. (1989) · JAMA · doi:10.1001/jama.1989.03430180093036 · Cited by 1,226 · see citing works
Kawarabayashi, T., Younkin, L. H., Saido, T. C., Shoji, M., Ashe, K. H., & Younkin, S. G. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-02-00372.2001 · Cited by 1,053 · cited 2× · see citing works
“These mice express the Swedish mutant of amyloid precursor protein in the brains and have amyloid plaques consisting of Ab increasing in an age-dependent manner (Hsiao et al. 1996; Kawarabayashi et al. 2001).”
Assembly and aggregation properties of synthetic Alzheimer's A4/beta amyloid peptide analogs.
Burdick, D., Soreghan, B., Kwon, M., Kosmoski, J., Knauer, M., Henschen, A., Yates, J., Cotman, C., & Glabe, C. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)48529-8 · Cited by 1,014 · see citing works
Scavenger receptor-mediated adhesion of microglia to β-amyloid fibrils
Khoury, J. E., Hickman, S. E., Thomas, C. A., Cao, L., Silverstein, S. C., & Loike, J. D. (1996) · Nature · doi:10.1038/382716a0 · Cited by 727 · see citing works
Amyloid β Protein (Aβ) in Alzheimeri's Disease Brain
Gravina, S. A., Ho, L., Eckman, C. B., Long, K. E., Otvos, L., Younkin, L. H., Suzuki, N., & Younkin, S. G. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.13.7013 · Cited by 676 · see citing works
Dong, H., Goico, B., Martin, M., Csernansky, C. A., Bertchume, A., & Csernansky, J. G. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.05.040 · Cited by 342 · cited 2× · see citing works
“Under stress conditions, IL-18 was also involved in the activation of murine microglia (Sugama et al. 2007), which accelerated learning and memory impairment and worsened the amyloid pathology in the mouse models of AD (Dong et al. 2004; Jeong et al. 2006).”
mRNA up-regulation of MHC II and pivotal pro-inflammatory genes in normal brain aging
Frank, M. G., Barrientos, R. M., Biedenkapp, J. C., Rudy, J. W., Watkins, L. R., & Maier, S. F. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.03.013 · Cited by 327 · see citing works
Implications for the kynurenine pathway and quinolinic acid in amyotrophic lateral sclerosis
Guillemin, G. J., Meininger, V., & Brew, B. J. (2005) · Neurodegenerative Diseases · doi:10.1159/000089622 · Cited by 105 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Kynurenines in CNS disease: regulation by inflammatory cytokines.
Campbell, B. M., Charych, E., Lee, A. W., & Möller, T. (2014) · Frontiers in Neuroscience · doi:10.3389/fnins.2014.00012 · Cited by 409 · see citing works
The kynurenine pathway and neurodegenerative disease
Maddison, D. C., & Giorgini, F. (2015) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2015.03.002 · Cited by 309 · see citing works
Microbial-derived metabolites as a risk factor of age-related cognitive decline and dementia
Connell, E., Le Gall, G., Pontifex, M. G., Sami, S., Cryan, J. F., Clarke, G., Müller, M., & Vauzour, D. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00548-6 · Cited by 208 · see citing works
Fongsaran, C., Dineley, K. T., Paessler, S., & Cisneros, I. E. (2024) · Pathogens · doi:10.3390/pathogens13050397 · Cited by 3 · see citing works
- Authors
- Yamada, A., Akimoto, H., Kagawa, S., Guillemin, G. J., & Takikawa, O.
- Affiliations
- National Center for Geriatrics and Gerontology (JP)
- St Vincent's Hospital Sydney (AU)
- Corresponding author
- Takikawa, Osamu
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2009-07-13
- Volume
- 110
- Issue
- 3
- Pages
- 791-800
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2041955403
- Cited by
- 58
- References
- 12
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 6 · 2022: 4 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 5 · 2017: 4 · 2016: 3 · 2015: 4 · 2014: 3 · 2013: 4 · 2012: 3
- FWCI
- 3.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- ACT Government
- Japan Society for the Promotion of Science (21590353)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- indoleamine 2,3-dioxygenase, interferon-gamma, amyloid beta peptide 1-42, microglia, kynurenine pathway, quinolinic acid, tryptophan metabolism, Alzheimer's disease, THP-1 cells, peripheral blood mononuclear cells, inflammatory cytokines, microglial activation, amyloid plaques, Tg2576 mice, lipopolysaccharide-induced inflammation
- MeSH terms
- Alzheimer Disease, Animals, Cells, Cultured, Enzyme Induction, Humans, Interferon-gamma, Kynurenine, Macrophage Activation, Monocytes, Peptide Fragments, Recombinant Proteins, Signal Transduction, Amyloid beta-Peptides, Inflammation Mediators, Cell Line, Tumor, Indoleamine-Pyrrole 2,3,-Dioxygenase, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
