title: Interleukin-1β induces an inflammatory response and the breakdown of the endothelial cell layer in an improved human THBMEC-based in vitro blood-brain barrier model.
abstract: BACKGROUND
  The blood-brain barrier is necessary to provide an optimal environment for cerebral function. It consists of endothelial cells that interact through interendothelial tight junctions and form a barrier with low permeability. Therefore, the infiltration of lymphocytes into the central nervous system is limited. Pathological conditions, such as chronic-inflammatory diseases and viral infections, induce a breakdown in the blood-brain barrier, which facilitates the accumulation of immune cells in the brain.
  
  
  METHODS
  Using the endothelial cell line "transfected human brain microvascular endothelial cells", we established an improved in vitro blood-brain barrier model. Using interleukin-1β, we refined this model into an inflammatory blood-brain barrier model.
  
  
  RESULTS
  The model is characterised by a transendothelial electrical resistance of 250 Ohm cm(2) and a permeability coefficient of 1×10(-6) cm/s for sodium fluorescein. IL-1β induces a strong inflammatory response, resulting in the increased expression of the adhesion molecule ICAM-1 and the pro-inflammatory cytokines IL-6, IL-8, and TNFα. Furthermore, the transendothelial electrical resistance decreased and the paracellular permeability increased in the presence of IL-1β. Additionally, the expression of the tight junction protein ZO-1 was reduced. As a consequence, an increased number of leukocytes were able to cross the cell layer.
  
  
  METHODS
  The model presented here exhibits improved characteristics with regards to TEER and permeability. The influence of IL-1β has not been described before in this model system.
  
  
  CONCLUSIONS
  The inflammatory in vitro blood-brain barrier model provides a useful tool for studying inflammatory processes at the blood-brain barrier, especially processes provoked by IL-1β.
authors.affiliation: Institute of Biochemistry, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: Josephine.labus@charite.de.
authors.forename: Josephine
authors.initials: J
authors.lastname: Labus
authors.affiliation: Institute of Biochemistry, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: Sonja.haeckel@charite.de.
authors.forename: Sonja
authors.initials: S
authors.lastname: Häckel
authors.affiliation: Institute of Biochemistry, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: lothar.lucka@charite.de.
authors.forename: Lother
authors.initials: L
authors.lastname: Lucka
authors.affiliation: Institute of Biochemistry, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: kerstin.danker@charite.de.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Danker
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D002461:Cell Line, Transformed; D003470:Culture Media / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D017097:Electric Impedance; D042783:Endothelial Cells; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology*; D007962:Leukocytes / Q000378:metabolism; D008954:Models, Biological; D062793:Occludin / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D057705:Transendothelial and Transepithelial Migration / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D003470:Culture Media; D016207:Cytokines; D053583:Interleukin-1beta; D062793:Occludin; C569042:TJP1 protein, human; D019010:Vascular Cell Adhesion Molecule-1; D062826:Zonula Occludens-1 Protein; D018799:Intercellular Adhesion Molecule-1
keywords: Blood–brain barrier; Inflammation; Interleukin-1β; THBMEC; Transmigration; Transwell model