dc.contributor.author |
OCarroll, Simon |
en |
dc.contributor.author |
Kho, Dan |
en |
dc.contributor.author |
Wiltshire, R |
en |
dc.contributor.author |
Nelson, Vicky |
en |
dc.contributor.author |
Mugisho, Odunayo |
en |
dc.contributor.author |
Johnson, Rebecca |
en |
dc.contributor.author |
Angel, Catherine |
en |
dc.contributor.author |
Graham, Euan |
en |
dc.date.accessioned |
2016-08-17T06:24:30Z |
en |
dc.date.issued |
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 |
http://hdl.handle.net/2292/30036 |
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 |
http://jneuroinflammation.biomedcentral.com/ |
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 http://www.sherpa.ac.uk/romeo/issn/1742-2094/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
en |
dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
en |
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 |
pubs.author-url |
http://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-015-0346-0 |
en |
pubs.end-page |
18 |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
490301 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
en |
pubs.org-id |
Anatomy and Medical Imaging |
en |
pubs.org-id |
Molecular Medicine |
en |
pubs.org-id |
Pharmacology |
en |
pubs.org-id |
School of Medicine |
en |
pubs.org-id |
Ophthalmology Department |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
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 |