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Cited by 32Alzheimer's disease research and treatmentsProtease and Inhibitor MechanismsNeuroinflammation and Neurodegeneration Mechanisms

An apolipoprotein E4 fragment affects matrix metalloproteinase 9, tissue inhibitor of metalloproteinase 1 and cytokine levels in brain cell lines

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Dafnis, I., Tzinia, A.K., Tsilibary, E.C., Zannis, V.I., Chroni, A.·2012·Neuroscience
DOI 10.1016/j.neuroscience.2012.03.013PMC PMC3358542
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Abstract

Apolipoprotein (apo) E4 isoform, a major risk factor for Alzheimer disease (AD), is more susceptible to proteolysis than apoE2 and apoE3 isoforms. ApoE4 fragments have been found in AD patients' brain. In the present study, we examined the effect of full-length apoE4 and apoE4 fragments apoE4[Δ(186-299)] and apoE4[Δ(166-299)] on inflammation in human neuroblastoma SK-N-SH and human astrocytoma SW-1783 cells. Western blot and zymography analysis showed that treatment of SK-N-SH cells with apoE4[Δ(186-299)], but not full-length apoE4 or the shorter apoE4[Δ(166-299)] fragment, leads to increased extracellular levels of matrix metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase 1 (TIMP1). Real-time PCR showed that interleukin (IL)-1β gene expression is also increased in SK-N-SH cells treated with apoE4[Δ(186-299)]. Treatment of SK-N-SH cells with IL-1β leads to increased MMP9 and TIMP1 extracellular levels, suggesting that the induction of IL-1β may be the mechanism by which apoE4[Δ(186-299)] regulates MMP9 and TIMP1 levels in these cells. In contrast to SK-N-SH cells, treatment of SW-1783 cells with apoE4[Δ(186-299)], and to a lesser extent with apoE4, leads to increased TIMP1 extracellular levels without affecting MMP9 levels. Additionally, apoE4[Δ(186-299)] leads to decreased IL-10 gene expression in SK-N-SH cells, whereas both apoE4 and apoE4[Δ(186-299)] lead to decreased TNFα gene expression without affecting IL-1β and IL-10 gene expression in SW-1783 cells. Overall, our findings indicate that a specific apoE4 fragment (apoE4[Δ(186-299)]), with molecular mass similar that of apoE4 fragments detected in AD patients' brain, can influence the level of inflammatory molecules in brain cell lines. It is possible that these phenomena contribute to AD pathogenesis.

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Cited by

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Authors
Dafnis, I., Tzinia, A. K., Tsilibary, E. C., Zannis, V. I., & Chroni, A.
Affiliations
  • National Centre of Scientific Research "Demokritos" (GR)
  • Boston University (US)
Corresponding author
Chroni, A.
ORCID
Venue
Neuroscience
Publisher
Elsevier BV
Published
2012-05
Volume
210
Pages
21-32
ISSN
0306-4522 (ISSN-L)
DOI
10.1016/j.neuroscience.2012.03.013
PMC
PMC3358542
OpenAlex
W2000205380
Cited by
32
References
10
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 5 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 4 · 2017: 4 · 2016: 1 · 2015: 2 · 2014: 5 · 2013: 3
FWCI
2.01
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (HL 68216, R01HL068216)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
APOE ε4, Alzheimer's disease, MMP-9, TIMP-1, IL-1β, IL-10, TNF-α, neuroinflammation, neuroblastoma cells, astrocytoma cells, proteolysis, gene expression regulation, extracellular matrix
MeSH terms
Alzheimer Disease, Astrocytes, Brain, Humans, Inflammation, Neurons, Peptide Fragments, Transfection, Blotting, Western, Cytokines, Tissue Inhibitor of Metalloproteinase-1, Matrix Metalloproteinase 9, Cell Line, Tumor, Apolipoprotein E4, Real-Time Polymerase Chain Reaction

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