Activation of glial cells induces proinflammatory properties in brain capillary endothelial cells in vitro
Abstract Neurodegenerative diseases are often accompanied by neuroinflammation and impairment of the blood-brain barrier (BBB) mediated by activated glial cells through their release of proinflammatory molecules. To study the effects of glial cells on mouse brain endothelial cells (mBECs), we develo...
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Nature Portfolio
2024-11-01
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| Online Access: | https://doi.org/10.1038/s41598-024-78204-w |
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| author | Annette Burkhart Steinunn Sara Helgudóttir Yahye A. Mahamed Mikkel B. Fruergaard Julie N. Holm-Jacobsen Hulda Haraldsdóttir Sara E. Dahl Freja Pretzmann Lisa Greve Routhe Kate Lambertsen Torben Moos Maj Schneider Thomsen |
| author_facet | Annette Burkhart Steinunn Sara Helgudóttir Yahye A. Mahamed Mikkel B. Fruergaard Julie N. Holm-Jacobsen Hulda Haraldsdóttir Sara E. Dahl Freja Pretzmann Lisa Greve Routhe Kate Lambertsen Torben Moos Maj Schneider Thomsen |
| author_sort | Annette Burkhart |
| collection | DOAJ |
| description | Abstract Neurodegenerative diseases are often accompanied by neuroinflammation and impairment of the blood-brain barrier (BBB) mediated by activated glial cells through their release of proinflammatory molecules. To study the effects of glial cells on mouse brain endothelial cells (mBECs), we developed an in vitro BBB model with inflammation by preactivating mixed glial cells (MGCs) with lipopolysaccharide (LPS) before co-culturing with mBECs to study the influence of molecules released by activated MGCs. The response of the mBECs to activated MGCs was compared to direct stimulation with LPS. The cytokine profile of activated MGCs was analyzed together with their effects on the mBEC’s integrity, expression of tight junction proteins, adhesion molecules, and BBB-specific transport proteins. Stimulation of MGCs significantly upregulated mRNA expression and secretion of several pro-inflammatory cytokines. Co-culturing mBECs with pre-stimulated MGCs significantly affected the barrier integrity of mBECs similar to direct stimulation with LPS. The gene expression levels of tight junction proteins were unaltered, but tight junction proteins revealed rearrangements with respect to subcellular distribution. Compared to direct stimulation with LPS, the expression of cell-adhesion molecules was significantly increased when mBECs were co-cultured with prestimulated MGCs and thus pre-activating MGCs transforms mBECs into a proinflammatory phenotype. |
| format | Article |
| id | doaj-art-77b46eebf90b409ab47df3068dca57dd |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-77b46eebf90b409ab47df3068dca57dd2025-08-20T02:50:07ZengNature PortfolioScientific Reports2045-23222024-11-0114111610.1038/s41598-024-78204-wActivation of glial cells induces proinflammatory properties in brain capillary endothelial cells in vitroAnnette Burkhart0Steinunn Sara Helgudóttir1Yahye A. Mahamed2Mikkel B. Fruergaard3Julie N. Holm-Jacobsen4Hulda Haraldsdóttir5Sara E. Dahl6Freja Pretzmann7Lisa Greve Routhe8Kate Lambertsen9Torben Moos10Maj Schneider Thomsen11Neurobiology Research and Drug Delivery, Department of Health Science and Technology, Aalborg UniversityNeurobiology Research and Drug Delivery, Department of Health Science and Technology, Aalborg UniversityNeurobiology Research and Drug Delivery, Department of Health Science and Technology, Aalborg UniversityNeurobiology Research and Drug Delivery, Department of Health Science and Technology, Aalborg UniversityNeurobiology Research and Drug Delivery, Department of Health Science and Technology, Aalborg UniversityNeurobiology Research and Drug Delivery, Department of Health Science and Technology, Aalborg UniversityNeurobiology Research and Drug Delivery, Department of Health Science and Technology, Aalborg UniversityNeurobiology Research and Drug Delivery, Department of Health Science and Technology, Aalborg UniversityNeurobiology Research and Drug Delivery, Department of Health Science and Technology, Aalborg UniversityNeurobiology Research, Department of Molecular Medicine, University of Southern DenmarkNeurobiology Research and Drug Delivery, Department of Health Science and Technology, Aalborg UniversityNeurobiology Research and Drug Delivery, Department of Health Science and Technology, Aalborg UniversityAbstract Neurodegenerative diseases are often accompanied by neuroinflammation and impairment of the blood-brain barrier (BBB) mediated by activated glial cells through their release of proinflammatory molecules. To study the effects of glial cells on mouse brain endothelial cells (mBECs), we developed an in vitro BBB model with inflammation by preactivating mixed glial cells (MGCs) with lipopolysaccharide (LPS) before co-culturing with mBECs to study the influence of molecules released by activated MGCs. The response of the mBECs to activated MGCs was compared to direct stimulation with LPS. The cytokine profile of activated MGCs was analyzed together with their effects on the mBEC’s integrity, expression of tight junction proteins, adhesion molecules, and BBB-specific transport proteins. Stimulation of MGCs significantly upregulated mRNA expression and secretion of several pro-inflammatory cytokines. Co-culturing mBECs with pre-stimulated MGCs significantly affected the barrier integrity of mBECs similar to direct stimulation with LPS. The gene expression levels of tight junction proteins were unaltered, but tight junction proteins revealed rearrangements with respect to subcellular distribution. Compared to direct stimulation with LPS, the expression of cell-adhesion molecules was significantly increased when mBECs were co-cultured with prestimulated MGCs and thus pre-activating MGCs transforms mBECs into a proinflammatory phenotype.https://doi.org/10.1038/s41598-024-78204-wBlood-brain barrierNeuroinflammationIn-vitro BBB modelGlial cellsLipopolysaccharide |
| spellingShingle | Annette Burkhart Steinunn Sara Helgudóttir Yahye A. Mahamed Mikkel B. Fruergaard Julie N. Holm-Jacobsen Hulda Haraldsdóttir Sara E. Dahl Freja Pretzmann Lisa Greve Routhe Kate Lambertsen Torben Moos Maj Schneider Thomsen Activation of glial cells induces proinflammatory properties in brain capillary endothelial cells in vitro Scientific Reports Blood-brain barrier Neuroinflammation In-vitro BBB model Glial cells Lipopolysaccharide |
| title | Activation of glial cells induces proinflammatory properties in brain capillary endothelial cells in vitro |
| title_full | Activation of glial cells induces proinflammatory properties in brain capillary endothelial cells in vitro |
| title_fullStr | Activation of glial cells induces proinflammatory properties in brain capillary endothelial cells in vitro |
| title_full_unstemmed | Activation of glial cells induces proinflammatory properties in brain capillary endothelial cells in vitro |
| title_short | Activation of glial cells induces proinflammatory properties in brain capillary endothelial cells in vitro |
| title_sort | activation of glial cells induces proinflammatory properties in brain capillary endothelial cells in vitro |
| topic | Blood-brain barrier Neuroinflammation In-vitro BBB model Glial cells Lipopolysaccharide |
| url | https://doi.org/10.1038/s41598-024-78204-w |
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