Inflammatory stress induced by a combination of cytokines (IL-6, IL-17, TNF-α) leads to a loss of integrity on bEnd.3 endothelial cells in vitro BBB model
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The brain is a complex organ protected by the blood-brain barrier (BBB), which also has a complex organization. To play its protective role, the BBB acts by limiting the paracellular passage of potentially cytotoxic compounds through tight junctions as well as limiting transcellular passage by efflux pumps (ABC transporters). In many conditions such as sleep apnea or Alzheimer's disease, there is chronic inflammation, resulting in the presence of pro-inflammatory cytokines in the bloodstream. The effect of this chronic inflammation on the integrity of the BBB has been studied mainly through a single inflammatory molecule; but in physiological and pathological conditions, it is a combination of inflammatory cytokines. We investigated the effect of three major pro-inflammatory cytokines (IL-17, IL-6, TNF-α) used alone or in combination on the integrity of an in vitro model of BBB. Our study showed 24 h of inflammatory stress led to a BBB's opening, reflected by a significant increase of permeability, which was correlated to a significant decrease of tight junction protein expressions (ZO-1, claudin-5), involving a possible entry of cytotoxic compounds into the brain. To compensate the loss of integrity, one of defense mechanism of endothelial cells was efflux transport, which showed a significant increase in expression and functionality of ABC transport proteins (MRP-1, Pgp). This opening of the BBB was more important when pro-inflammatory cytokines were combined, which could be explained by the interaction between cytokines and the potentiation of their effect.
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Stimulation of endothelial cells with Aβ or proinflammatory cytokines reduced expression of tight junction proteins Claudin-5, VE-cadherin and Occludin, thus increasing permeability.
“Multiple in vitro experiments revealed that stimulation of endothelial cells with Aβ or proinflammatory cytokines reduced the expression of tight junction proteins like Claudin-5, VE-cadherin and Occludin, thus increased permeability.474–478”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [475]
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- Authors
- Voirin, A.-C., Perek, N., & Roche, F.
- Affiliations
- Inserm (FR)
- Centre Hospitalier Universitaire de Saint-Étienne (FR)
- Corresponding author
- Voirin, Anne-Cloé
- ORCID
- Roche, Frédéric
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2020-03
- Volume
- 1730
- Pages
- 146647
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2998040352
- Cited by
- 99
- References
- 9
- Citations by year
- 2026: 18 · 2025: 19 · 2024: 20 · 2023: 13 · 2022: 11 · 2021: 12 · 2020: 6
- FWCI
- 4.08
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Brain Research (acceptedVersion, other-oa)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by-nc)
- HAL (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- blood-brain barrier integrity, inflammatory cytokines, interleukin-6, IL-17, TNF-α, endothelial cells, bEnd.3 cells, tight junction proteins, claudin-5, ZO-1, ABC transporters, MRP1, P-glycoprotein, blood-brain barrier permeability, chronic inflammation, sleep apnea, Alzheimer's disease, cytokine combinations
- MeSH terms
- Animals, Blood-Brain Barrier, Cell Line, Encephalitis, Stress, Physiological, Tumor Necrosis Factor-alpha, Interleukin-6, Cytokines, ATP-Binding Cassette Transporters, Interleukin-17, Endothelial Cells, Mice, Claudin-5, Zonula Occludens-1 Protein
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