4.4 Article

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

期刊

JOURNAL OF NEUROSCIENCE METHODS
卷 228, 期 -, 页码 35-45

出版社

ELSEVIER
DOI: 10.1016/j.jneumeth.2014.03.002

关键词

Blood-brain barrier; Transwell model; THBMEC; Transmigration; Inflammation; Interleukin-1 beta

资金

  1. Sonnenfeld-Stiftung
  2. Free University Berlin

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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. New method: Using the endothelial cell line transfected human brain microvascular endothelial cells, we established an improved in vitro blood-brain barrier model. Using interleukin-1 beta, 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 x 10(-6) cm/s for sodium fluorescein. IL-1 beta 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 TNF alpha. Furthermore, the transendothelial electrical resistance decreased and the paracellular permeability increased in the presence of IL-1 beta. 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 methods: The model presented here exhibits improved characteristics with regards to TEER and permeability. The influence of IL-1 beta has not been described before in this model system. Conclusion: 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-1 beta. (C) 2014 Elsevier B.V. All rights reserved.

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