Costimulatory Effects of Interferon-γ and Interleukin-1β or Tumor Necrosis Factor α on the Synthesis of Aβ1-40 and Aβ1-42 by Human Astrocytes
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Chronic inflammation and astrocytosis are characteristic histopathological features of Alzheimer's Disease (AD). Astrocytes are one of the predominant cell types in the brain. In AD they are activated and produce inflammatory components such as complement components, acute phase proteins, and cytokines. In this study we analyzed the effect of cytokines on the production of amyloid beta (Abeta) in the astrocytoma cell line U373 and in primary human astrocytes isolated postmortem from healthy aged persons as well as from patients with AD. Astrocytes did not produce Abeta in the absence of stimuli or following stimulation with IL-1beta, TNFalpha, IL-6, and TGF-beta1. Neither did combinations of TNFalpha and IL-1beta, IL-6 or TGF-beta1, or the coadministration of IFNgamma and IL-6 or TGF-beta1 induce Abeta production. In contrast, pronounced production of Abeta1-40 and Abeta1-42 was observed when primary astrocytes or astrocytoma cells were stimulated with combinations of IFNgamma and TNFalpha or IFNgamma and IL-1beta. Induction of Abeta production was accompanied by decreased glycosylation of APP as well as by increased secretion of APPsbeta. Our results suggest that astrocytes may be an important source of Abeta in the presence of certain combinations of inflammatory cytokines. IFNgamma in combination with TNFalpha or IL-1beta seems to trigger Abeta production by supporting beta-secretase cleavage of the immature APP molecule.
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Combined stimulation of IL-1β, IL-6, and IFN-γ induces APP production and increased Aβ levels.
“combined stimulation of IL-1β, IL-6, and IFN-γ in U373 glioblastoma cell lines and primary human astrocytes could induce APP production and lead to increased Aβ levels (Blasko et al., 2000).”
From AD-Like Neuropsychiatric Dysfunction in a Mice Model Induced by a Combination of High-Fat Diet and Intraperitoneal Injection of Streptozotocin (2024) · cites this paper as Blasko et al., 2000
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- Authors
- Blasko, I., Veerhuis, R., Stampfer-Kountchev, M., Saurwein-Teissl, M., Eikelenboom, P., & Grubeck-Loebenstein, B.
- Affiliations
- Austrian Academy of Sciences (AT)
- Vrije Universiteit Amsterdam (NL)
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2000-12
- Volume
- 7
- Issue
- 6
- Pages
- 682-689
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2156877034
- Cited by
- 258
- References
- 5
- Citations by year
- 2026: 10 · 2025: 6 · 2024: 18 · 2023: 17 · 2022: 20 · 2021: 20 · 2020: 8 · 2019: 14 · 2018: 13 · 2017: 15 · 2016: 12 · 2015: 9 · 2014: 16 · 2013: 8 · 2012: 3
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- green
- research.vumc.nl
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- amyloid-beta, amyloid-β1-40, amyloid-beta 42, astrocytes, interferon-gamma, IL-1β, TNF-α, Alzheimer's disease, chronic inflammation, astrocyte activation, cytokine combinations
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Astrocytes, Astrocytoma, Cells, Cultured, Drug Synergism, Female, Glycosylation, Humans, Interferon-gamma, Interleukin-1, Male, Middle Aged, Peptide Fragments, Protein Processing, Post-Translational, Tumor Necrosis Factor-alpha, Interleukin-6, Cytokines, Transforming Growth Factor beta, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Transforming Growth Factor beta1
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