Pro-inflammatory TNFα and IL-1β differentially regulate the inflammatory phenotype of brain microvascular endothelial cells

Show simple item record OCarroll, Simon en Kho, Dan en Wiltshire, R en Nelson, Vicky en Mugisho, Odunayo en Johnson, Rebecca en Angel, Catherine en Graham, Euan en 2016-08-17T06:24:30Z en 2015-07-08 en
dc.identifier.citation Journal of Neuroinflammation, 12: 131, pp. 1-18 en
dc.identifier.issn 1742-2094 en
dc.identifier.uri en
dc.description.abstract Background: The vasculature of the brain is composed of endothelial cells, pericytes and astrocytic processes. The endothelial cells are the critical interface between the blood and the CNS parenchyma and are a critical component of the blood-brain barrier (BBB). These cells are innately programmed to respond to a myriad of inflammatory cytokines or other danger signals. IL-1β and TNFα are well recognised pro-inflammatory mediators, and here, we provide compelling evidence that they regulate the function and immune response profile of human cerebral microvascular endothelial cells (hCMVECs) differentially. Methods: We used xCELLigence biosensor technology, which revealed global differences in the endothelial response between IL-1β and TNFα. xCELLigence is a label-free impedance-based biosensor, which is ideal for acute or long-term comparison of drug effects on cell behaviour. In addition, flow cytometry and multiplex cytokine arrays were used to show differences in the inflammatory responses from the endothelial cells. Results: Extensive cytokine-secretion profiling and cell-surface immune phenotyping confirmed that the immune response of the hCMVEC to IL-1β was different to that of TNFα. Interestingly, of the 38 cytokines, chemokines and growth factors measured by cytometric bead array, the endothelial cells secreted only 13. Of importance was the observation that the majority of these cytokines were differentially regulated by either IL-1β or TNFα. Cell-surface expression of ICAM-1 and VCAM-1 were also differentially regulated by IL-1β or TNFα, where TNFα induced a substantially higher level of expression of both key leukocyte-adhesion molecules. A range of other cell-surface cellular and junctional adhesion molecules were basally expressed by the hCMVEC but were unaffected by IL-1β or TNFα. Conclusions: To our knowledge, this is the most comprehensive analysis of the immunological profile of brain endothelial cells and the first direct evidence that human brain endothelial cells are differentially regulated by these two key pro-inflammatory mediators. en
dc.description.uri en
dc.publisher BioMed Central en
dc.relation.ispartofseries Journal of Neuroinflammation en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from en
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dc.subject Brain en
dc.subject Cell Line en
dc.subject Endothelial Cells en
dc.subject Humans en
dc.subject Encephalitis en
dc.subject Tumor Necrosis Factor-alpha en
dc.subject Intercellular Adhesion Molecule-1 en
dc.subject Vascular Cell Adhesion Molecule-1 en
dc.subject Cytokines en
dc.subject Immunophenotyping en
dc.subject Phenotype en
dc.subject Interleukin-1beta en
dc.subject Microvessels en
dc.subject Tight Junction Proteins en
dc.title Pro-inflammatory TNFα and IL-1β differentially regulate the inflammatory phenotype of brain microvascular endothelial cells en
dc.type Journal Article en
dc.identifier.doi 10.1186/s12974-015-0346-0 en
pubs.begin-page 1 en
pubs.volume 12 en
dc.description.version VoR – Version of Record en
dc.rights.holder Copyright: The Authors en
dc.identifier.pmid 26152369 en en
pubs.end-page 18 en
pubs.publication-status Published en
dc.rights.accessrights en
pubs.subtype Article en
pubs.elements-id 490301 en Medical and Health Sciences en Medical Sciences en Anatomy and Medical Imaging en Molecular Medicine en Pharmacology en School of Medicine en Ophthalmology Department en Science en Biological Sciences en
dc.identifier.eissn 1742-2094 en
pubs.number 131 en
pubs.record-created-at-source-date 2016-08-17 en
pubs.dimensions-id 26152369 en

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