Unique and shared inflammatory profiles of human brain endothelia and pericytes.

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dc.contributor.author Smyth, Leon en
dc.contributor.author Rustenhoven, Justin en
dc.contributor.author Park, In en
dc.contributor.author Schweder, Patrick en
dc.contributor.author Jansson, Deidre en
dc.contributor.author Heppner, Peter A en
dc.contributor.author OCarroll, Simon en
dc.contributor.author Mee, Edward W en
dc.contributor.author Faull, Richard en
dc.contributor.author Curtis, Maurice en
dc.contributor.author Dragunow, Michael en
dc.date.accessioned 2019-09-30T03:33:03Z en
dc.date.issued 2018-05-11 en
dc.identifier.citation Journal of neuroinflammation 15(1):138 11 May 2018 en
dc.identifier.issn 1742-2094 en
dc.identifier.uri http://hdl.handle.net/2292/48071 en
dc.description.abstract BACKGROUND:Pericytes and endothelial cells are critical cellular components of the blood-brain barrier (BBB) and play an important role in neuroinflammation. To date, the majority of inflammation-related studies in endothelia and pericytes have been carried out using immortalised cell lines or non-human-derived cells. Whether these are representative of primary human cells is unclear and systematic comparisons of the inflammatory responses of primary human brain-derived pericytes and endothelia has yet to be performed. METHODS:To study the effects of neuroinflammation at the BBB, primary brain endothelial cells and pericytes were isolated from human biopsy tissue. Culture purity was examined using qPCR and immunocytochemistry. Electrical cell-substrate impedance sensing (ECIS) was used to determine the barrier properties of endothelial and pericyte cultures. Using immunocytochemistry, cytometric bead array, and ECIS, we compared the responses of endothelia and pericytes to a panel of inflammatory stimuli (IL-1β, TNFα, LPS, IFN-γ, TGF-β1, IL-6, and IL-4). Secretome analysis was performed to identify unique secretions of endothelia and pericytes in response to IL-1β. RESULTS:Endothelial cells were pure, moderately proliferative, retained the expression of BBB-related junctional proteins and transporters, and generated robust TEER. Both endothelia and pericytes have the same pattern of transcription factor activation in response to inflammatory stimuli but respond differently at the secretion level. Secretome analysis confirmed that endothelia and pericytes have overlapping but distinct secretome profiles in response to IL-1β. We identified several cell-type specific responses, including G-CSF and GM-CSF (endothelial-specific), and IGFBP2 and IGFBP3 (pericyte-specific). Finally, we demonstrated that direct addition of IL-1β, TNFα, LPS, and IL-4 contributed to the loss of endothelial barrier integrity in vitro. CONCLUSIONS:Here, we identify important cell-type differences in the inflammatory response of brain pericytes and endothelia and provide, for the first time, a comprehensive profile of the secretions of primary human brain endothelia and pericytes which has implications for understanding how inflammation affects the cerebrovasculature. en
dc.format.medium Electronic en
dc.language eng 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. 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.subject Blood-Brain Barrier en
dc.subject Pericytes en
dc.subject Brain en
dc.subject Cells, Cultured en
dc.subject Endothelial Cells en
dc.subject Humans en
dc.subject Inflammation en
dc.subject Inflammation Mediators en
dc.subject Coculture Techniques en
dc.title Unique and shared inflammatory profiles of human brain endothelia and pericytes. en
dc.type Journal Article en
dc.identifier.doi 10.1186/s12974-018-1167-8 en
pubs.issue 1 en
pubs.begin-page 138 en
pubs.volume 15 en
dc.rights.holder Copyright: The authors en
dc.identifier.pmid 29751771 en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/OpenAccess en
pubs.subtype research-article en
pubs.subtype Journal Article en
pubs.elements-id 740801 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 Pharmacology en
dc.identifier.eissn 1742-2094 en
pubs.record-created-at-source-date 2018-05-13 en
pubs.dimensions-id 29751771 en

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