Activation of glial cells induces proinflammatory properties in brain capillary endothelial cells in vitro

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

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

1 Citation (Scopus)
2 Downloads (Pure)

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.

Original languageEnglish
Article number26580
JournalScientific Reports
Volume14
Issue number1
ISSN2045-2322
DOIs
Publication statusPublished - 4 Nov 2024

Bibliographical note

© 2024. The Author(s).

Keywords

  • Animals
  • Blood-Brain Barrier/metabolism
  • Brain/metabolism
  • Cells, Cultured
  • Coculture Techniques
  • Cytokines/metabolism
  • Endothelial Cells/metabolism
  • Inflammation/metabolism
  • Lipopolysaccharides/pharmacology
  • Mice
  • Neuroglia/metabolism
  • Tight Junction Proteins/metabolism

Fingerprint

Dive into the research topics of 'Activation of glial cells induces proinflammatory properties in brain capillary endothelial cells in vitro'. Together they form a unique fingerprint.

Cite this