IL-1β promotes transendothelial migration of PBMCs by upregulation of the FN/α5β1 signalling pathway in immortalised human brain microvascular endothelial cells

Josephine Labus, Kerstin Wöltje, Kim Natalie Stolte, Sonja Häckel, Kwang Sik Kim, Annette Hildmann, Kerstin Danker

Research output: Contribution to journalArticlepeer-review

Abstract

Neuroinflammation is often associated with pathological changes in the function of the blood-brain barrier (BBB) caused by disassembly of tight and adherens junctions that under physiological conditions are important for the maintenance of the BBB integrity. Consequently, in inflammation the BBB becomes dysfunctional, facilitating leukocyte traversal of the barrier and accumulation of immune cells within the brain. The extracellular matrix (ECM) also contributes to BBB integrity but the significance of the main ECM receptors, the β1 integrins also expressed on endothelial cells, is less well understood. To evaluate whether β1 integrin function is affected during inflammation and impacts barrier function, we used a transformed human brain microvascular endothelial cell (THBMEC)-based Interleukin 1β (IL-1β)-induced inflammatory in vitro BBB model. We demonstrate that IL-1β increases cell-matrix adhesion and induces a redistribution of active β1 integrins to the basal surface. In particular, binding of α5β1 integrin to its ligand fibronectin is enhanced and α5β1 integrin-dependent signalling is upregulated. Additionally, localisation of the tight junction protein claudin-5 is altered. Blockade of the α5β1 integrin reduces the IL-1β-induced transendothelial migration of peripheral blood mononuclear cells (PBMCs). These data imply that IL-1β-induced inflammation not only destabilizes tight junctions but also increases α5β1 integrin-dependent cell-matrix adhesion to fibronectin.

Original languageEnglish (US)
Pages (from-to)99-111
Number of pages13
JournalExperimental cell research
Volume373
Issue number1-2
DOIs
StatePublished - Dec 15 2018

Keywords

  • Actin
  • Blood-brain barrier
  • FAK
  • Fibronectin
  • Src
  • Transendothelial migration
  • αβ integrin

ASJC Scopus subject areas

  • Cell Biology

Fingerprint Dive into the research topics of 'IL-1β promotes transendothelial migration of PBMCs by upregulation of the FN/α<sub>5</sub>β<sub>1</sub> signalling pathway in immortalised human brain microvascular endothelial cells'. Together they form a unique fingerprint.

Cite this