Basic NeuroscienceInterleukin-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

- A blood-brain barrier model based on the THBMEC cell line was improved.
- A novel inflammatory blood-brain barrier model was established.
- IL-1β induced a strong inflammatory response in this model.

BackgroundThe 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.New methodUsing 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.ResultsThe model is characterised by a transendothelial electrical resistance of 250 Ohm cm2 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.Comparison with existing methodsThe 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.ConclusionThe 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.