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
| Autor: | Nathalie Perek, Anne-Cloé Voirin, Frédéric Roche |
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| Přispěvatelé: | Système Nerveux Autonome - Epidémiologie, Physiologie, Ingénierie, Santé (SNA-EPIS), Université Jean Monnet [Saint-Étienne] (UJM)-Centre Hospitalier Universitaire de Saint-Etienne, Biologie intégrative du tissu osseux, Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), CCSD, Accord Elsevier |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
[SDV]Life Sciences [q-bio] Inflammation Blood–brain barrier Cell Line Proinflammatory cytokine Mice 03 medical and health sciences 0302 clinical medicine Stress Physiological medicine Animals Cytotoxic T cell Claudin-5 Transcellular Molecular Biology Tight junction Interleukin-6 Tumor Necrosis Factor-alpha Chemistry General Neuroscience Interleukin-17 Endothelial Cells Cell biology [SDV] Life Sciences [q-bio] 030104 developmental biology medicine.anatomical_structure Blood-Brain Barrier Paracellular transport Zonula Occludens-1 Protein Cytokines Encephalitis ATP-Binding Cassette Transporters Neurology (clinical) Interleukin 17 medicine.symptom 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Brain Research Brain Research, 2020, 1730, pp.146647-. ⟨10.1016/j.brainres.2020.146647⟩ Brain Research, Elsevier, 2020, 1730, pp.146647-. ⟨10.1016/j.brainres.2020.146647⟩ |
| ISSN: | 0006-8993 |
| DOI: | 10.1016/j.brainres.2020.146647⟩ |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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