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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2016

Open Access 01-12-2016 | Research

Interferon-γ blocks signalling through PDGFRβ in human brain pericytes

Authors: Deidre Jansson, Emma L. Scotter, Justin Rustenhoven, Natacha Coppieters, Leon C. D. Smyth, Robyn L. Oldfield, Peter S. Bergin, Edward W. Mee, E. Scott Graham, Richard L. M. Faull, Mike Dragunow

Published in: Journal of Neuroinflammation | Issue 1/2016

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Abstract

Background

Neuroinflammation and blood-brain barrier (BBB) disruption are common features of many brain disorders, including Alzheimer’s disease, epilepsy, and motor neuron disease. Inflammation is thought to be a driver of BBB breakdown, but the underlying mechanisms for this are unclear. Brain pericytes are critical cells for maintaining the BBB and are immunologically active. We sought to test the hypothesis that inflammation regulates the BBB by altering pericyte biology.

Methods

We exposed primary adult human brain pericytes to chronic interferon-gamma (IFNγ) for 4 days and measured associated functional aspects of pericyte biology. Specifically, we examined the influence of inflammation on platelet-derived growth factor receptor-beta (PDGFRβ) expression and signalling, as well as pericyte proliferation and migration by qRT-PCR, immunocytochemistry, flow cytometry, and western blotting.

Results

Chronic IFNγ treatment had marked effects on pericyte biology most notably through the PDGFRβ, by enhancing agonist (PDGF-BB)-induced receptor phosphorylation, internalization, and subsequent degradation. Functionally, chronic IFNγ prevented PDGF-BB-mediated pericyte proliferation and migration.

Conclusions

Because PDGFRβ is critical for pericyte function and its removal leads to BBB leakage, our results pinpoint a mechanism linking chronic brain inflammation to BBB dysfunction.
Appendix
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Metadata
Title
Interferon-γ blocks signalling through PDGFRβ in human brain pericytes
Authors
Deidre Jansson
Emma L. Scotter
Justin Rustenhoven
Natacha Coppieters
Leon C. D. Smyth
Robyn L. Oldfield
Peter S. Bergin
Edward W. Mee
E. Scott Graham
Richard L. M. Faull
Mike Dragunow
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2016
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-016-0722-4

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